Trial Outcomes & Findings for Trametinib and Akt Inhibitor GSK2141795 in Treating Patients With Metastatic Triple-Negative Breast Cancer (NCT NCT01964924)

NCT ID: NCT01964924

Last Updated: 2019-09-20

Results Overview

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 37 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2019-09-20

Participant Flow

Patients on Part 1: trametinib monotherapy until progression and then will continue on to Part 2: trametinib combined with GSK2141795.

Participant milestones

Measure	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 1: PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression in Part 1 continue to Part 2.	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2: PART 2: Patients who experience disease progression in Part 1 continue to Part 2. Patients receive trametinib and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO
Trametinib Monotherapy STARTED	37	0
Trametinib Monotherapy COMPLETED	18	0
Trametinib Monotherapy NOT COMPLETED	19	0
Trametinib + GSK2141 STARTED	0	19
Trametinib + GSK2141 COMPLETED	0	19
Trametinib + GSK2141 NOT COMPLETED	0	0

Reasons for withdrawal

Measure	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 1: PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression in Part 1 continue to Part 2.	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2: PART 2: Patients who experience disease progression in Part 1 continue to Part 2. Patients receive trametinib and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO
Trametinib Monotherapy Progression	19	0

Baseline Characteristics

Trametinib and Akt Inhibitor GSK2141795 in Treating Patients With Metastatic Triple-Negative Breast Cancer

Baseline characteristics by cohort

Measure	Treatment (Trametinib, Akt Inhibitor GSK2141795) n=37 Participants PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2. PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO
Age, Continuous	57 years n=5 Participants
Sex: Female, Male Female	37 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	37 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	31 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	37 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Measure	Treatment (Trametinib, Akt Inhibitor GSK2141795) n=37 Participants PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2. PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2: PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO
Objective Response Rate (ORR), Defined as the Proportion of Patients Who Have Had a Partial Response (PR) or Complete Response (CR) (RECIST 1.1 Based) Within the First 6 Months After Initiation of Therapy With Trametinib	2 Participants	—

SECONDARY outcome

Timeframe: Up to 52 weeks

The clinical benefit rate (CR+PR+SD) will be reported for patients after Part 1 and after Part 2.

Outcome measures

Measure	Treatment (Trametinib, Akt Inhibitor GSK2141795) n=37 Participants PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2. PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2: n=19 Participants PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO
Clinical Benefit Rate (CBR = CR+PR+Stable Disease [SD])	8 Participants	6 Participants

SECONDARY outcome

Timeframe: up to 52 weeks

Summary statistics of duration of response for patients with objective response

Outcome measures

Measure	Treatment (Trametinib, Akt Inhibitor GSK2141795) n=8 Participants PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2. PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2: n=6 Participants PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO
Duration of Objective Response	162.75 days of response Standard Deviation 149.26	87.00 days of response Standard Deviation 62.86

SECONDARY outcome

Timeframe: Up to 52 weeks

Incidence of adverse events for patients that are classified as either possibly, probably, or definitely related to study treatment graded by National Cancer Institute (NCI) CTCAE v4.0

Outcome measures

Measure	Treatment (Trametinib, Akt Inhibitor GSK2141795) n=37 Participants PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2. PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2: n=19 Participants PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO
Incidence of Adverse Events That Are Classified as Either Possibly, Probably, or Definitely Related to Study Treatment	227 number of adverse events	204 number of adverse events

SECONDARY outcome

Timeframe: Up to 52 weeks

NCI CommonTerminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for grading incidence of toxicities (grade 3+).

Outcome measures

Measure	Treatment (Trametinib, Akt Inhibitor GSK2141795) n=37 Participants PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2. PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2: n=19 Participants PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO
Incidence of Severe (Grade 3+) Adverse Events or Toxicities Graded Per NCI CTCAE Version 4.0	68 number of adverse events	29 number of adverse events

SECONDARY outcome

Timeframe: Start date of the treatment to the date of the event (i.e., death) or the date of last follow-up to evaluate that event, assessed up to 52 weeks

Population: overall survival analyzed for all patients regardless of (part 1 only) or (part 1 and 2) participation

The Kaplan-Meier method will be used to estimate overall survival distribution.

Outcome measures

Measure	Treatment (Trametinib, Akt Inhibitor GSK2141795) n=37 Participants PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2. PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2: PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO
Overall Survival	43.143 weeks Interval 33.0 to 99.286	—

SECONDARY outcome

Timeframe: The duration of time from start of treatment to time of progression or death, whichever comes first, assessed up to 52 weeks

The Kaplan-Meier method will be used to estimate progression-free survival distribution.

Outcome measures

Measure	Treatment (Trametinib, Akt Inhibitor GSK2141795) n=37 Participants PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2. PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2: n=19 Participants PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO
Progression-free Survival	7.71 weeks Interval 4.43 to 8.29	7.86 weeks Interval 5.86 to 13.86

SECONDARY outcome

Timeframe: Up to 52 weeks

The proportion of patients who go off treatment due to adverse reactions or even those who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial was captured. These tolerability measures were assessed within each of the treatment parts independently. All patients who have received at least one dose of any of the therapeutic agents was evaluable for toxicity and tolerability.

Outcome measures

Measure	Treatment (Trametinib, Akt Inhibitor GSK2141795) n=37 Participants PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2. PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2: n=19 Participants PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO
Proportion of Patients Who go Off Treatment Due to Adverse Reactions	4 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 52 weeks

Population: The proportion of patients who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial was in Part I

Outcome measures

Measure	Treatment (Trametinib, Akt Inhibitor GSK2141795) n=37 Participants PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2. PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2: PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO
Proportion of Patients Who Refuse Further Treatment for Lesser Toxicities That Inhibit Their Willingness to Continue Participation on the Trial	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 52 weeks

Outcome measures

Measure	Treatment (Trametinib, Akt Inhibitor GSK2141795) n=37 Participants PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2. PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2: n=19 Participants PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO
Tolerability of the Regimen Defined as the Number of Patients Who Required Dose Modifications and/or Dose Delays	35 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: At time of disease progression, assessed up to 52 weeks

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 52 weeks

Ratios between tumors sampled prior to initiating trametinib single agent treatment and at time of progression (TOP) on either single agent trametinib or the combination (TOP/pre-treat ratio), will be calculated. These ratios will be median-centered and clustered using Cluster 2.0 software. Student's t-test for differences between average protein intensity ratios at these intervals will be calculated using Microsoft Excel by grouping all the ratios for individual clusters.

Outcome measures

Outcome data not reported

Adverse Events

Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 1:

Serious events: 30 serious events

Other events: 37 other events

Deaths: 13 deaths

Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2:

Serious events: 15 serious events

Other events: 19 other events

Deaths: 12 deaths

Serious adverse events

Measure	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 1: n=37 participants at risk PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2.	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2: n=19 participants at risk PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Investigations Alkaline phosphatase increased	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Blood and lymphatic system disorders Anemia	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Reproductive system and breast disorders Breast pain	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Cardiac disorders Cardiac arrest	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
General disorders Death NOS	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	21.1% 4/19 • Number of events 4 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Metabolism and nutrition disorders Dehydration	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Gastrointestinal disorders Diarrhea	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	10.5% 2/19 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Gastrointestinal disorders Dysphagia	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Respiratory, thoracic and mediastinal disorders Dyspnea	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
General disorders Edema face	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
General disorders Edema limbs	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Gastrointestinal disorders Enterocolitis	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
General disorders Fever	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
General disorders General disorders and administration site conditions - Other, specify	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Vascular disorders Hypertension	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Metabolism and nutrition disorders Hypoalbuminemia	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Metabolism and nutrition disorders Hypocalcemia	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Nervous system disorders Hypoglossal nerve disorder	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Metabolism and nutrition disorders Hypoglycemia	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Infections and infestations Infections and infestations - Other, specify	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Blood and lymphatic system disorders Leukocytosis	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	21.6% 8/37 • Number of events 8 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	15.8% 3/19 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Musculoskeletal and connective tissue disorders Pain in extremity	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Renal and urinary disorders Renal and urinary disorders - Other, specify	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Infections and infestations Sepsis	5.4% 2/37 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Infections and infestations Skin infection	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Nervous system disorders Syncope	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Vascular disorders Thromboembolic event	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Ear and labyrinth disorders Vertigo	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Gastrointestinal disorders Vomiting	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0

Other adverse events

Measure	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 1: n=37 participants at risk PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2.	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2: n=19 participants at risk PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Gastrointestinal disorders Abdominal distension	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Gastrointestinal disorders Abdominal pain	8.1% 3/37 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Investigations Alanine aminotransferase increased	18.9% 7/37 • Number of events 7 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	10.5% 2/19 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Investigations Alkaline phosphatase increased	16.2% 6/37 • Number of events 6 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	15.8% 3/19 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Skin and subcutaneous tissue disorders Alopecia	8.1% 3/37 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Blood and lymphatic system disorders Anemia	18.9% 7/37 • Number of events 7 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	42.1% 8/19 • Number of events 8 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Metabolism and nutrition disorders Anorexia	13.5% 5/37 • Number of events 5 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	10.5% 2/19 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Psychiatric disorders Anxiety	10.8% 4/37 • Number of events 4 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Musculoskeletal and connective tissue disorders Arthralgia	5.4% 2/37 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Investigations Aspartate aminotransferase increased	35.1% 13/37 • Number of events 13 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	21.1% 4/19 • Number of events 4 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Musculoskeletal and connective tissue disorders Back pain	8.1% 3/37 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	21.1% 4/19 • Number of events 4 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Eye disorders Blurred vision	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	10.5% 2/19 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Reproductive system and breast disorders Breast pain	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Injury, poisoning and procedural complications Bruising	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Gastrointestinal disorders Colitis	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Gastrointestinal disorders Constipation	13.5% 5/37 • Number of events 5 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Respiratory, thoracic and mediastinal disorders Cough	8.1% 3/37 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	10.5% 2/19 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Investigations Creatinine increased	10.8% 4/37 • Number of events 4 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	15.8% 3/19 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Metabolism and nutrition disorders Dehydration	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	26.3% 5/19 • Number of events 5 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Psychiatric disorders Depression	10.8% 4/37 • Number of events 4 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Gastrointestinal disorders Diarrhea	29.7% 11/37 • Number of events 11 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	84.2% 16/19 • Number of events 16 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Nervous system disorders Dizziness	8.1% 3/37 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Gastrointestinal disorders Dry mouth	10.8% 4/37 • Number of events 4 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Skin and subcutaneous tissue disorders Dry skin	13.5% 5/37 • Number of events 5 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	21.1% 4/19 • Number of events 4 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Nervous system disorders Dysgeusia	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	10.5% 2/19 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Gastrointestinal disorders Dyspepsia	10.8% 4/37 • Number of events 4 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Gastrointestinal disorders Dysphagia	5.4% 2/37 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	26.3% 5/19 • Number of events 5 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Nervous system disorders Dysphasia	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	10.5% 2/19 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Respiratory, thoracic and mediastinal disorders Dyspnea	24.3% 9/37 • Number of events 9 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	42.1% 8/19 • Number of events 8 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
General disorders Edema face	10.8% 4/37 • Number of events 4 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
General disorders Edema limbs	29.7% 11/37 • Number of events 11 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	21.1% 4/19 • Number of events 4 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
General disorders Edema trunk	5.4% 2/37 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Investigations Ejection fraction decreased	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Investigations Electrocardiogram QT corrected interval prolonged	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	10.5% 2/19 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Respiratory, thoracic and mediastinal disorders Epistaxis	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	15.8% 3/19 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Gastrointestinal disorders Esophageal pain	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
General disorders Facial pain	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Injury, poisoning and procedural complications Fall	5.4% 2/37 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
General disorders Fatigue	29.7% 11/37 • Number of events 11 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	31.6% 6/19 • Number of events 6 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
General disorders Fever	8.1% 3/37 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Musculoskeletal and connective tissue disorders Flank pain	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
General disorders Flu like symptoms	5.4% 2/37 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Gastrointestinal disorders Gastroesophageal reflux disease	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	5.4% 2/37 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	10.5% 2/19 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Musculoskeletal and connective tissue disorders Generalized muscle weakness	8.1% 3/37 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	10.5% 2/19 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Nervous system disorders Headache	10.8% 4/37 • Number of events 4 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Cardiac disorders Heart failure	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Renal and urinary disorders Hematuria	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Respiratory, thoracic and mediastinal disorders Hoarseness	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Metabolism and nutrition disorders Hyperglycemia	18.9% 7/37 • Number of events 7 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	31.6% 6/19 • Number of events 8 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Vascular disorders Hypertension	13.5% 5/37 • Number of events 5 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	36.8% 7/19 • Number of events 9 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Endocrine disorders Hyperthyroidism	5.4% 2/37 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Metabolism and nutrition disorders Hypoalbuminemia	24.3% 9/37 • Number of events 9 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	36.8% 7/19 • Number of events 8 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Metabolism and nutrition disorders Hypocalcemia	8.1% 3/37 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	21.1% 4/19 • Number of events 5 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Metabolism and nutrition disorders Hypoglycemia	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Metabolism and nutrition disorders Hypokalemia	8.1% 3/37 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	10.5% 2/19 • Number of events 6 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Metabolism and nutrition disorders Hypomagnesemia	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Metabolism and nutrition disorders Hyponatremia	8.1% 3/37 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Vascular disorders Hypotension	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Endocrine disorders Hypothyroidism	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	10.5% 2/19 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Respiratory, thoracic and mediastinal disorders Hypoxia	5.4% 2/37 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Investigations INR increased	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Infections and infestations Infections and infestations - Other, specify	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	15.8% 3/19 • Number of events 4 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Psychiatric disorders Insomnia	5.4% 2/37 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	10.5% 2/19 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Investigations Investigations - Other, specify	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	10.5% 2/19 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Cardiac disorders Left ventricular systolic dysfunction	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
General disorders Localized edema	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Vascular disorders Lymphedema	13.5% 5/37 • Number of events 5 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	10.5% 2/19 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Investigations Lymphocyte count decreased	16.2% 6/37 • Number of events 6 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	21.1% 4/19 • Number of events 4 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Nervous system disorders Movements involuntary	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Gastrointestinal disorders Mucositis oral	10.8% 4/37 • Number of events 4 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	63.2% 12/19 • Number of events 13 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Skin and subcutaneous tissue disorders Nail ridging	5.4% 2/37 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Respiratory, thoracic and mediastinal disorders Nasal congestion	5.4% 2/37 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Gastrointestinal disorders Nausea	32.4% 12/37 • Number of events 12 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	26.3% 5/19 • Number of events 6 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
General disorders Neck edema	5.4% 2/37 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps-Other	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	10.5% 2/19 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Investigations Neutrophil count decreased	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	10.5% 2/19 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
General disorders Non-cardiac chest pain	5.4% 2/37 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	15.8% 3/19 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
General disorders Pain	10.8% 4/37 • Number of events 4 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	10.5% 2/19 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Musculoskeletal and connective tissue disorders Pain in extremity	10.8% 4/37 • Number of events 4 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	10.5% 2/19 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Infections and infestations Paronychia	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	10.5% 2/19 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Nervous system disorders Peripheral motor neuropathy	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Nervous system disorders Peripheral sensory neuropathy	13.5% 5/37 • Number of events 5 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	21.1% 4/19 • Number of events 4 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Investigations Platelet count decreased	18.9% 7/37 • Number of events 7 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	15.8% 3/19 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Respiratory, thoracic and mediastinal disorders Pleural effusion	13.5% 5/37 • Number of events 5 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	15.8% 3/19 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Nervous system disorders Presyncope	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Skin and subcutaneous tissue disorders Pruritus	16.2% 6/37 • Number of events 6 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	15.8% 3/19 • Number of events 5 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Skin and subcutaneous tissue disorders Rash acneiform	27.0% 10/37 • Number of events 10 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	15.8% 3/19 • Number of events 5 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Skin and subcutaneous tissue disorders Rash maculo-papular	16.2% 6/37 • Number of events 6 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	15.8% 3/19 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Cardiac disorders Sinus tachycardia	8.1% 3/37 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	10.8% 4/37 • Number of events 4 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	15.8% 3/19 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Infections and infestations Skin infection	5.4% 2/37 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Respiratory, thoracic and mediastinal disorders Sore throat	5.4% 2/37 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	0.00% 0/19 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Vascular disorders Thromboembolic event	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Renal and urinary disorders Urinary frequency	5.4% 2/37 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	10.5% 2/19 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Infections and infestations Urinary tract infection	5.4% 2/37 • Number of events 2 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Injury, poisoning and procedural complications Vascular access complication	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Cardiac disorders Ventricular tachycardia	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Respiratory, thoracic and mediastinal disorders Voice alteration	0.00% 0/37 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Gastrointestinal disorders Vomiting	16.2% 6/37 • Number of events 6 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	15.8% 3/19 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Investigations Weight gain	8.1% 3/37 • Number of events 3 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	5.3% 1/19 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Investigations Weight loss	2.7% 1/37 • Number of events 1 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	15.8% 3/19 • Number of events 4 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0
Investigations White blood cell decreased	13.5% 5/37 • Number of events 5 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0	31.6% 6/19 • Number of events 7 • Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study. Adverse Event grading was done using NCI CTCAE version 4.0

Additional Information

Bhuvaneswari Ramaswamy

The Ohio State University Comprehensive Cancer Center

Phone: 614-293-8858

Email: Bhuvaneswari.Ramaswamy@osumc.edu

Results disclosure agreements

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

Restriction type: LTE60