Trial Outcomes & Findings for Expanded Phase I Pazopanib and Everolimus in Advanced Solid Tumors and Previously Treated Advanced Urothelial Cancer (NCT NCT01184326)

NCT ID: NCT01184326

Last Updated: 2019-10-02

Results Overview

The MTD of Pazopanib in combination with Everolimus 5 mg PO QD was determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of patients experience a DLT. If no DLTs are observed, the MTD is not reached.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 23 participants
• Primary outcome timeframe: Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; The observation period for MTD evaluation was the first 28 days of treatment.
• Results posted on: 2019-10-02

Participant Flow

Participants were enrolled between January 2011 and July 2016 including dose finding 1/1/2011-9/23/2011 and expansion 3/9/2015-7/25/2016.

Participant milestones

Measure	Dose Level 0: Everolimus 5mg + Pazopanib 600 mg Everolimus 5mg + Pazopanib 600 mg once daily for 28 days each cycle Participants were treated until disease progression, unacceptable toxicity or patient withdrawal.	Dose Level -1: Everolimus 5mg + Pazopanib 400 mg Everolimus 5mg + Pazopanib 400 mg once daily for 28 days each cycle Participants were treated until disease progression, unacceptable toxicity or patient withdrawal.	All Phase I Dose Expansion Participants All phase I dose expansion participants received Everolimus 5mg and Pazopanib at the maximum tolerated dose established in the dose finding part of the study.
Overall Study STARTED	3	6	14
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	3	6	14

Reasons for withdrawal

Measure	Dose Level 0: Everolimus 5mg + Pazopanib 600 mg Everolimus 5mg + Pazopanib 600 mg once daily for 28 days each cycle Participants were treated until disease progression, unacceptable toxicity or patient withdrawal.	Dose Level -1: Everolimus 5mg + Pazopanib 400 mg Everolimus 5mg + Pazopanib 400 mg once daily for 28 days each cycle Participants were treated until disease progression, unacceptable toxicity or patient withdrawal.	All Phase I Dose Expansion Participants All phase I dose expansion participants received Everolimus 5mg and Pazopanib at the maximum tolerated dose established in the dose finding part of the study.
Overall Study Adverse Event	1	2	0
Overall Study Death	0	0	1
Overall Study Withdrawal by Subject	0	0	1
Overall Study Physician Decision	1	1	0
Overall Study Disease Progression	1	3	12

Baseline Characteristics

Expanded Phase I Pazopanib and Everolimus in Advanced Solid Tumors and Previously Treated Advanced Urothelial Cancer

Baseline characteristics by cohort

Measure	Dose Level 0: Everolimus 5mg + Pazopanib 600 mg n=3 Participants Everolimus 5mg + Pazopanib 600 mg once daily for 28 days each cycle Participants were treated until disease progression, unacceptable toxicity or patient withdrawal.	Dose Level -1: Everolimus 5mg + Pazopanib 400 mg n=6 Participants Everolimus 5mg + Pazopanib 400 mg once daily for 28 days each cycle Participants were treated until disease progression, unacceptable toxicity or patient withdrawal.	All Phase I Dose Expansion Participants n=14 Participants All phase I dose expansion participants received Everolimus 5mg and Pazopanib at the maximum tolerated dose established in the dose finding part of the study.	Total n=23 Participants Total of all reporting groups
Age, Continuous	61 years n=5 Participants	58 years n=7 Participants	69 years n=5 Participants	66 years n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	2 Participants n=7 Participants	12 Participants n=5 Participants	17 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized White	3 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants	21 Participants n=4 Participants
Region of Enrollment United States	3 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants	23 Participants n=4 Participants
Tumor type Adrenal cortex	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Tumor type Bladder	3 Participants n=5 Participants	2 Participants n=7 Participants	14 Participants n=5 Participants	19 Participants n=4 Participants
Tumor type Lung	0 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants

PRIMARY outcome

Timeframe: Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; The observation period for MTD evaluation was the first 28 days of treatment.

Population: All phase I dose finding participants who received at least one dose of the study drug were evaluable for MTD.

The MTD of Pazopanib in combination with Everolimus 5 mg PO QD was determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of patients experience a DLT. If no DLTs are observed, the MTD is not reached.

Outcome measures

Measure	All Phase I Dose Finding Participants n=9 Participants All phase I dose finding participants received Everolimus 5mg and Pazopanib according to the established dose escalation schedule.	Dose Level -1: Everolimus 5mg + Pazopanib 400 mg Everolimus 5mg + Pazopanib 400 mg once daily for 28 days each cycle Participants were treated until disease progression, unacceptable toxicity or patient withdrawal.
Maximum Tolerated Dose (MTD) [Phase I Dose Finding]	400 mg	—

PRIMARY outcome

Timeframe: Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; The observation period for DLT evaluation was the first 28 days of treatment.

Population: All phase I dose finding participants who received at least one dose of the study drug were evaluable for DLT.

A DLT was defined as an adverse event (a) with treatment attribution of possible, probable, or definite, and (b) occurs during cycle 1, and (c) meets any of the following criteria: Grade 3 or 4 non-hematologic toxicity excluding: nausea/vomiting controlled with antiemetics, Grade 3 hypertension that resolves to ≤150/90 within 7 days with supportive care, and Grade 3 asymptomatic, clinically insignificant laboratory abnormalities (LDH, alkaline phosphatase due to bone metastases, and asymptomatic hypophosphatemia). Hematologic toxicity: Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with bleeding, Grade 4 neutropenia which persists for >7 days, Grade 4 neutropenia associated with fever >38.5C; Hematologic toxicity excluded lymphopenia or anemia of any grade. Missing more than 5 days of planned doses for drug-related intolerable grade 2 toxicity;Toxicity related to therapy severe enough to require a dose-reduction.

Outcome measures

Measure	All Phase I Dose Finding Participants n=3 Participants All phase I dose finding participants received Everolimus 5mg and Pazopanib according to the established dose escalation schedule.	Dose Level -1: Everolimus 5mg + Pazopanib 400 mg n=6 Participants Everolimus 5mg + Pazopanib 400 mg once daily for 28 days each cycle Participants were treated until disease progression, unacceptable toxicity or patient withdrawal.
Dose Limiting Toxicity (DLT) [Phase I Dose Finding]	2 Participants	0 Participants

PRIMARY outcome

Timeframe: TDisease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment duration was up to 6 cycles in the Dose Level 0 cohort, 14 cycles in the Dose Level -1 cohort and 10 cycles in the expansion cohort (1 cycle=28 days).

Population: The analysis population is comprised of all enrolled Phase 1 expansion participants.

The objective response rate (ORR) was defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

Outcome measures

Measure	All Phase I Dose Finding Participants n=14 Participants All phase I dose finding participants received Everolimus 5mg and Pazopanib according to the established dose escalation schedule.	Dose Level -1: Everolimus 5mg + Pazopanib 400 mg Everolimus 5mg + Pazopanib 400 mg once daily for 28 days each cycle Participants were treated until disease progression, unacceptable toxicity or patient withdrawal.
Objective Response Rate [Expansion]	21.4 percentage of participants Interval 4.7 to 50.8	—

SECONDARY outcome

Timeframe: Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 6 cycles in the Dose Level 0 cohort and 14 cycles in the Dose Level -1 cohort (1 cycle=28 days).

Population: All phase I dose finding participants who received at least one dose of the study drug were evaluable for toxicity.

Grade 4 treatment-related toxicity rate is the percentage of participants experiencing at least one treatment-related grade 4 adverse event (AE) with treatment attribution of possibly, probably or definite based on NCI Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4) as reported on case report forms.

Outcome measures

Measure	All Phase I Dose Finding Participants n=3 Participants All phase I dose finding participants received Everolimus 5mg and Pazopanib according to the established dose escalation schedule.	Dose Level -1: Everolimus 5mg + Pazopanib 400 mg n=6 Participants Everolimus 5mg + Pazopanib 400 mg once daily for 28 days each cycle Participants were treated until disease progression, unacceptable toxicity or patient withdrawal.
Grade 4 Treatment-Related Toxicity Rate [Dose Finding]	33.3 percentage of participants Interval 0.9 to 90.6	0.0 percentage of participants Interval 0.0 to 45.9

SECONDARY outcome

Timeframe: Disease was evaluated radiologically at baseline and every 8 weeks on treatment; PFS follow-up was up to 9.2 months in the expansion cohort.

Population: The analysis population is comprised of all enrolled Phase 1 expansion participants.

Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Participants alive without PD are censored at date of last disease assessment. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum longest diameter (LD), taking as reference the smallest sum on study with at least 5 mm absolute increase or the appearance of one or more new lesions. For non-target lesions, PD is appearance of one or more new lesions or unequivocal progression of existing non-target lesions.

Outcome measures

Measure	All Phase I Dose Finding Participants n=14 Participants All phase I dose finding participants received Everolimus 5mg and Pazopanib according to the established dose escalation schedule.	Dose Level -1: Everolimus 5mg + Pazopanib 400 mg Everolimus 5mg + Pazopanib 400 mg once daily for 28 days each cycle Participants were treated until disease progression, unacceptable toxicity or patient withdrawal.
Median Progression-Free Survival [Expansion]	2.9 months Interval 0.9 to 3.6	—

SECONDARY outcome

Timeframe: Disease was evaluated radiologically at baseline and every 8 weeks on treatment; PFS follow-up was up to 9.2 months in the expansion cohort.

Population: The duration of response is only estimated in the phase 1 expansion participants who achieved objective response on treatment.

Duration of response was calculated as the time from achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment until disease progression. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. For target lesions: PD is at least a 20% increase in sum longest diameter (LD), taking as reference the smallest sum on study with at least 5 mm absolute increase or the appearance of one or more new lesions. For non-target lesions, PD is appearance of one or more new lesions or unequivocal progression of existing non-target lesions.

Outcome measures

Measure	All Phase I Dose Finding Participants n=14 Participants All phase I dose finding participants received Everolimus 5mg and Pazopanib according to the established dose escalation schedule.	Dose Level -1: Everolimus 5mg + Pazopanib 400 mg Everolimus 5mg + Pazopanib 400 mg once daily for 28 days each cycle Participants were treated until disease progression, unacceptable toxicity or patient withdrawal.
Mean Duration of Response [Expansion]	4.9 months Interval 1.7 to 7.4	—

SECONDARY outcome

Timeframe: Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 10 cycles in the expansion cohort (1 cycle=28 days).

Population: All phase I expansion participants who received at least one dose of the study drug were evaluable for toxicity.

Grade 4 treatment-related toxicity rate is the percentage of participants experiencing at least one treatment-related grade 4 adverse event (AE) with treatment attribution of possibly, probably or definite based on NCI Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4) as reported on case report forms.

Outcome measures

Measure	All Phase I Dose Finding Participants n=14 Participants All phase I dose finding participants received Everolimus 5mg and Pazopanib according to the established dose escalation schedule.	Dose Level -1: Everolimus 5mg + Pazopanib 400 mg Everolimus 5mg + Pazopanib 400 mg once daily for 28 days each cycle Participants were treated until disease progression, unacceptable toxicity or patient withdrawal.
Grade 4 Treatment-Related Toxicity Rate [Expansion]	7.1 percentage of participants Interval 0.2 to 33.9	—

Adverse Events

Dose Level 0: Everolimus 5mg + Pazopanib 600 mg

Serious events: 3 serious events

Other events: 3 other events

Deaths: 3 deaths

Dose Level -1: Everolimus 5mg + Pazopanib 400 mg

Serious events: 2 serious events

Other events: 6 other events

Deaths: 6 deaths

All Phase I Dose Expansion Participants

Serious events: 13 serious events

Other events: 13 other events

Deaths: 9 deaths

Serious adverse events

Measure	Dose Level 0: Everolimus 5mg + Pazopanib 600 mg n=3 participants at risk Everolimus 5mg + Pazopanib 600 mg once daily for 28 days each cycle Participants were treated until disease progression, unacceptable toxicity or patient withdrawal.	Dose Level -1: Everolimus 5mg + Pazopanib 400 mg n=6 participants at risk All phase I dose expansion participants received Everolimus 5mg and Pazopanib at the maximum tolerated dose established in the dose finding part of the study.	All Phase I Dose Expansion Participants n=14 participants at risk All phase I dose expansion participants received Everolimus 5mg and Pazopanib at the maximum tolerated dose established in the dose finding part of the study.
Investigations Alanine aminotransferase increased	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Investigations Aspartate aminotransferase increased	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	14.3% 2/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Gastrointestinal disorders Diarrhea	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
General disorders Fatigue	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	14.3% 2/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
General disorders General disorders and administration site conditions (other)	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Infections and infestations Hepatitis viral	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Metabolism and nutrition disorders Hyperuricemia	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Metabolism and nutrition disorders Hypophosphatemia	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	21.4% 3/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Nervous system disorders Intracranial hemorrhage	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Investigations Lipase increased	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	33.3% 2/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Investigations Lymphocyte count decreased	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Gastrointestinal disorders Mucositis oral	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Investigations Neutrophil count decreased	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Gastrointestinal disorders Pancreatitis	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Investigations Platelet count decreased	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Respiratory, thoracic and mediastinal disorders Pneumothorax	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Skin and subcutaneous tissue disorders Pruritus	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Skin and subcutaneous tissue disorders Rash maculo-papular	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.

Other adverse events

Measure	Dose Level 0: Everolimus 5mg + Pazopanib 600 mg n=3 participants at risk Everolimus 5mg + Pazopanib 600 mg once daily for 28 days each cycle Participants were treated until disease progression, unacceptable toxicity or patient withdrawal.	Dose Level -1: Everolimus 5mg + Pazopanib 400 mg n=6 participants at risk All phase I dose expansion participants received Everolimus 5mg and Pazopanib at the maximum tolerated dose established in the dose finding part of the study.	All Phase I Dose Expansion Participants n=14 participants at risk All phase I dose expansion participants received Everolimus 5mg and Pazopanib at the maximum tolerated dose established in the dose finding part of the study.
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	33.3% 2/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	14.3% 2/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Investigations Alanine aminotransferase increased	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	50.0% 3/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	28.6% 4/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Investigations Alkaline phosphatase increased	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Blood and lymphatic system disorders Anemia	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	50.0% 3/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Metabolism and nutrition disorders Anorexia	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	33.3% 2/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	42.9% 6/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Psychiatric disorders Anxiety	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Investigations Aspartate aminotransferase increased	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	50.0% 3/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	35.7% 5/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Investigations Blood bilirubin increased	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	21.4% 3/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Cardiac disorders Cardiac disorder other	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Investigations Cholesterol high	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	33.3% 2/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	14.3% 2/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Gastrointestinal disorders Constipation	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	28.6% 4/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Investigations Creatinine increased	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Psychiatric disorders Depression	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Gastrointestinal disorders Diarrhea	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	33.3% 2/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	50.0% 7/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Nervous system disorders Dizziness	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Nervous system disorders Dysgeusia	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	21.4% 3/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	14.3% 2/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
General disorders Edema limbs	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	21.4% 3/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
General disorders Edema trunk	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Respiratory, thoracic and mediastinal disorders Epistaxis	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
General disorders Fatigue	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	83.3% 5/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	42.9% 6/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Investigations GGT increased	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
General disorders Gait disturbance	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Gastrointestinal disorders Gastroesophageal reflux disease	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
General disorders Fever	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	33.3% 2/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
General disorders General disorders and administration site conditions (other)	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Nervous system disorders Headache	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Renal and urinary disorders Hematuria	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	50.0% 3/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	42.9% 6/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Metabolism and nutrition disorders Hypermagnesemia	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Vascular disorders Hypertension	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	33.3% 2/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	14.3% 2/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Endocrine disorders Hyperthyroidism	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Metabolism and nutrition disorders Hypertriglyceridemia	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	33.3% 2/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	28.6% 4/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Metabolism and nutrition disorders Hyperuricemia	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Metabolism and nutrition disorders Hypoalbuminemia	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Metabolism and nutrition disorders Hypocalcemia	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	50.0% 3/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	50.0% 3/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Metabolism and nutrition disorders Hypomagnesemia	66.7% 2/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	21.4% 3/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	14.3% 2/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Metabolism and nutrition disorders Hypophosphatemia	66.7% 2/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	33.3% 2/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	42.9% 6/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Investigations INR increased	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications (other)	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Psychiatric disorders Insomnia	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Respiratory, thoracic and mediastinal disorders Laryngeal inflammation	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Gastrointestinal disorders Lip pain	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Investigations Lipase increased	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	14.3% 2/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Infections and infestations Lung infection	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Metabolism and nutrition disorders Metabolism and nutrition disorders (other)	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Gastrointestinal disorders Mucosal infection	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Gastrointestinal disorders Mucositis oral	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	50.0% 3/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	21.4% 3/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Gastrointestinal disorders Nausea	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	66.7% 4/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	14.3% 2/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Nervous system disorders Nervous system disorders (other)	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Investigations Neutrophil count decreased	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
General disorders Pain	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Skin and subcutaneous tissue disorders Pain of skin	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Reproductive system and breast disorders Pelvic pain	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Nervous system disorders Phantom pain	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Nervous system disorders Peripheral motor neuropathy	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Investigations Platelet count decreased	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	66.7% 4/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	35.7% 5/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	21.4% 3/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Renal and urinary disorders Proteinuria	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Skin and subcutaneous tissue disorders Rash acneiform	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	33.3% 2/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	28.6% 4/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Investigations Serum amylase increased	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	33.3% 2/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	21.4% 3/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Skin and subcutaneous tissue disorders Skin infection	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Cardiac disorders Supraventricular tachycardia	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	33.3% 2/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Vascular disorders Thromboembolic event	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Ear and labyrinth disorders Tinnitus	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Renal and urinary disorders Urinary frequency	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Infections and infestations Urinary tract infection	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Injury, poisoning and procedural complications Vascular access complication	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	0.00% 0/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Gastrointestinal disorders Vomiting	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	50.0% 3/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	7.1% 1/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Investigations Weight loss	33.3% 1/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	33.3% 2/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	28.6% 4/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.
Investigations White blood cell decreased	0.00% 0/3 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	16.7% 1/6 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.	14.3% 2/14 • Participants were assessed for adverse events on days 1 and 15 for cycles 1-2 and every cycle thereafter; Treatment duration was up to 13 cycles in this study cohort (1 cycle=28 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.

Additional Information

Dr. Mark Pomerantz

Dana-Farber Cancer Institute

Phone: 617-632-4524

Email: mark_pomerantz@dfci.harvard.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place