Trial Outcomes & Findings for Tivantinib in Treating Patients With Metastatic Prostate Cancer (NCT NCT01519414)

NCT ID: NCT01519414

Last Updated: 2018-09-12

Results Overview

The progression-free survival distributions between the two arms will be compared using log-rank tests. Progression-free survival curves will be constructed using the Kaplan-Meier product limit method, and additional analyses will be done using the Cox proportional hazards model.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

78 participants

Primary outcome timeframe

Time from study entry to the date of documented progression and/or death, assessed up to 6 months

Results posted on

2018-09-12

Participant Flow

Participant milestones

Participant milestones
Measure	Arm I (Tivantinib) Patients receive tivantinib 360 mg (3 \* 120 mg tablets) po BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm II (Placebo) Patients receive matched placebo (3 tablets) po BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I.	Crossover From Placebo to Tivantinib Patients who were originally assigned to placebo and experience disease progression will be allowed to crossover and take ARQ 197. The treatment plan, duration of therapy, criteria for progression and follow-up will be the same as described above for men originally assigned to ARQ 197.
Pre Cross-over STARTED	52	26	0
Pre Cross-over COMPLETED	52	26	0
Pre Cross-over NOT COMPLETED	0	0	0
Post Cross-over STARTED	52	14	12
Post Cross-over COMPLETED	52	14	12
Post Cross-over NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Tivantinib in Treating Patients With Metastatic Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Tivantinib) n=52 Participants Patients receive tivantinib 360 mg (3 \* 120 mg tablets) po BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm II (Placebo) n=26 Participants Patients receive matched placebo (3 tablets) po BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I.	Total n=78 Participants Total of all reporting groups
Age, Continuous	67 years n=5 Participants	66.5 years n=7 Participants	67 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	52 Participants n=5 Participants	26 Participants n=7 Participants	78 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) White	49 Participants n=5 Participants	20 Participants n=7 Participants	69 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	52 patients n=5 Participants	26 patients n=7 Participants	78 patients n=5 Participants

PRIMARY outcome

Timeframe: Time from study entry to the date of documented progression and/or death, assessed up to 6 months

Outcome measures

Outcome measures
Measure	Arm I (Tivantinib) n=52 Participants Patients receive tivantinib 360 mg (3 \* 120 mg tablets) po BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm II (Placebo) n=26 Participants Patients receive matched placebo (3 tablets) po BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I.	Crossover From Placebo to Tivantinib Patients who were originally assigned to placebo and experience disease progression will be allowed to crossover and take ARQ 197. The treatment plan, duration of therapy, criteria for progression and follow-up will be the same as described above for men originally assigned to ARQ 197.
Progression-free Survival (PFS) Based on the RECIST Criteria	5.5 months Interval 3.2 to 8.0	3.7 months Interval 2.7 to 5.4	—

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Evaluated and patterns graphically explored through waterfall plots.

Outcome measures

Outcome measures
Measure	Arm I (Tivantinib) n=52 Participants Patients receive tivantinib 360 mg (3 \* 120 mg tablets) po BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm II (Placebo) n=26 Participants Patients receive matched placebo (3 tablets) po BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I.	Crossover From Placebo to Tivantinib Patients who were originally assigned to placebo and experience disease progression will be allowed to crossover and take ARQ 197. The treatment plan, duration of therapy, criteria for progression and follow-up will be the same as described above for men originally assigned to ARQ 197.
Changes in PSA Levels	140.1 percentage change from baseline Interval -9.0 to 5768.1	301.5 percentage change from baseline Interval -3.3 to 3254.4	—

SECONDARY outcome

Timeframe: At 12 weeks

An assumed binomial distribution used. Summarized with their corresponding 95% binomial confidence intervals and compared in an exploratory manner between the two treatment arms. Dichotomized outcomes of response will be descriptively summarized and graphically evaluated using bar graphs.

Outcome measures

Outcome measures
Measure	Arm I (Tivantinib) n=52 Participants Patients receive tivantinib 360 mg (3 \* 120 mg tablets) po BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm II (Placebo) n=26 Participants Patients receive matched placebo (3 tablets) po BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I.	Crossover From Placebo to Tivantinib n=12 Participants Patients who were originally assigned to placebo and experience disease progression will be allowed to crossover and take ARQ 197. The treatment plan, duration of therapy, criteria for progression and follow-up will be the same as described above for men originally assigned to ARQ 197.
Proportion of Patients Who Respond	1.9 percentage of patients Interval 0.05 to 10.26	0 percentage of patients Interval 0.0 to 0.0	8.3 percentage of patients Interval 0.2 to 38.5

SECONDARY outcome

Timeframe: up to 12 weeks

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

Outcome measures
Measure	Arm I (Tivantinib) n=52 Participants Patients receive tivantinib 360 mg (3 \* 120 mg tablets) po BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm II (Placebo) n=26 Participants Patients receive matched placebo (3 tablets) po BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I.	Crossover From Placebo to Tivantinib n=12 Participants Patients who were originally assigned to placebo and experience disease progression will be allowed to crossover and take ARQ 197. The treatment plan, duration of therapy, criteria for progression and follow-up will be the same as described above for men originally assigned to ARQ 197.
PSA Response Rate	1.9 percentage of patients Interval 0.05 to 10.26	0 percentage of patients Interval 0.0 to 0.0	8.3 percentage of patients Interval 0.2 to 38.5

SECONDARY outcome

Timeframe: Up to 1 year

Population: Adverse events graded as 3, 4 or 5 per NCI CTCAE version 4 (regardless of attribution)

Fisher's exact tests will be used to quantitatively compare the incidence of severe as well as specific toxicities of interest between the treatment arms and graphically assessed differences in maximum grades observed for toxicities between the arms.

Outcome measures

Outcome measures
Measure	Arm I (Tivantinib) n=52 Participants Patients receive tivantinib 360 mg (3 \* 120 mg tablets) po BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm II (Placebo) n=26 Participants Patients receive matched placebo (3 tablets) po BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I.	Crossover From Placebo to Tivantinib n=12 Participants Patients who were originally assigned to placebo and experience disease progression will be allowed to crossover and take ARQ 197. The treatment plan, duration of therapy, criteria for progression and follow-up will be the same as described above for men originally assigned to ARQ 197.
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Fall	0 patients	1 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Lymph gland infection	1 patients	0 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Syncope	0 patients	2 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Upper respiratory infection	0 patients	1 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Acute coronary syndrome	1 patients	0 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Alkaline phosphatase increased	0 patients	0 patients	2 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Anemia	3 patients	0 patients	2 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Back pain	1 patients	1 patients	1 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Confusion	0 patients	2 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Cataract	1 patients	0 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Death NOS	1 patients	0 patients	1 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Dehydration	0 patients	2 patients	1 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Dizziness	0 patients	1 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Duodenal ulcer	1 patients	0 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Dyspnea	0 patients	1 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Enterocolitis infectious	0 patients	1 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Fatigue	2 patients	0 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Febrile neutropenia	1 patients	0 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Gait disturbance	0 patients	1 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Generalized muscle weakness	0 patients	1 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Hypertension	1 patients	0 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Hypokalemia	0 patients	1 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Hyponatremia	1 patients	0 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Hypotension	0 patients	1 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Hypoxia	1 patients	1 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Infections and infestations - Other, specify	1 patients	0 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Lymphocyte count decreased	2 patients	2 patients	2 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Musculoskeletal and connective tissue disorder - O	0 patients	1 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Neoplasms benign, malignant and unspecified (incl	1 patients	1 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Nervous system disorders - Other, specify	0 patients	1 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Neutrophil count decreased	2 patients	0 patients	2 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Platelet count decreased	1 patients	0 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Pleural effusion	0 patients	0 patients	1 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Productive cough	0 patients	0 patients	1 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Sinus bradycardia	3 patients	0 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Sinus tachycardia	0 patients	1 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Thromboembolic event	0 patients	1 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Tumor pain	1 patients	0 patients	0 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 Urinary tract obstruction	0 patients	0 patients	1 patients
Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 White blood cell decreased	2 patients	0 patients	2 patients

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 12 weeks

Summarized with their corresponding 95% binomial confidence intervals and compared in an exploratory manner between the two treatment arms. Dichotomized outcomes of response will be descriptively summarized and graphically evaluated using bar graphs.

Outcome measures

Outcome measures
Measure	Arm I (Tivantinib) n=52 Participants Patients receive tivantinib 360 mg (3 \* 120 mg tablets) po BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm II (Placebo) n=26 Participants Patients receive matched placebo (3 tablets) po BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I.	Crossover From Placebo to Tivantinib n=12 Participants Patients who were originally assigned to placebo and experience disease progression will be allowed to crossover and take ARQ 197. The treatment plan, duration of therapy, criteria for progression and follow-up will be the same as described above for men originally assigned to ARQ 197.
Radiographic Response Rate Based on RECIST Criteria	1.9 percentage of patients Interval 0.05 to 10.26	0 percentage of patients Interval 0.0 to 0.0	8.3 percentage of patients Interval 0.2 to 38.5

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to up to 6 months

BSAP will first be descriptively summarized by treatment group and also evaluated using graphical analyses to assess potential patterns over time and see if changes in bone resorption differ between those who are progression-free at 12 weeks vs. not after treatment with tivantinib. The potential impact of early changes in these markers on PFS using Cox regression models will be also explored.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to up to 6 months

NTx and CTX will first be descriptively summarized by treatment group and also evaluated using graphical analyses to assess potential patterns over time and see if changes in bone resorption differ between those who are progression-free at 12 weeks vs. not after treatment with tivantinib. The potential impact of early changes in these markers on PFS using Cox regression models will be also explored.

Outcome measures

Outcome data not reported

Adverse Events

Arm I (Tivantinib)

Serious events: 19 serious events

Other events: 52 other events

Deaths: 7 deaths

Arm II (Placebo)

Serious events: 22 serious events

Other events: 26 other events

Deaths: 4 deaths

Crossover From Placebo to Tivantinib

Serious events: 5 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Paul Monk, MD

The Ohio State University Comprehensive Cancer Center

Phone: (614) 293-6196

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Arm I (Tivantinib) n=52 participants at risk Patients receive tivantinib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm II (Placebo) n=26 participants at risk Patients receive placebo PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I.	Crossover From Placebo to Tivantinib n=12 participants at risk Patients who were originally assigned to placebo and experience disease progression will be allowed to crossover and take ARQ 197. The treatment plan, duration of therapy, criteria for progression and follow-up will be the same as described above for men originally assigned to ARQ 197.
Blood and lymphatic system disorders Anemia	1.9% 1/52 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/26 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Cardiac disorders Acute coronary syndrome	1.9% 1/52 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/26 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Cardiac disorders Sinus bradycardia	1.9% 1/52 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/26 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Cardiac disorders Sinus tachycardia	0.00% 0/52 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	3.8% 1/26 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Gastrointestinal disorders Abdominal pain	0.00% 0/52 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	3.8% 1/26 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Gastrointestinal disorders Constipation	1.9% 1/52 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/26 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Gastrointestinal disorders Diarrhea	0.00% 0/52 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	3.8% 1/26 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Gastrointestinal disorders Duodenal ulcer	1.9% 1/52 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/26 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Gastrointestinal disorders Nausea	1.9% 1/52 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/26 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
General disorders Death NOS	1.9% 1/52 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/26 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	8.3% 1/12 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
General disorders Edema limbs	1.9% 1/52 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/26 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	8.3% 1/12 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
General disorders Fatigue	1.9% 1/52 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/26 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	8.3% 1/12 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
General disorders Fever	1.9% 1/52 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/26 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
General disorders Gait disturbance	0.00% 0/52 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	3.8% 1/26 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Infections and infestations Enterocolitis infectious	0.00% 0/52 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	3.8% 1/26 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Infections and infestations Infections and infestations - Other, specify	1.9% 1/52 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/26 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Infections and infestations Upper respiratory infection	0.00% 0/52 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	3.8% 1/26 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Injury, poisoning and procedural complications Fall	0.00% 0/52 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	3.8% 1/26 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Metabolism and nutrition disorders Anorexia	1.9% 1/52 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/26 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Metabolism and nutrition disorders Dehydration	0.00% 0/52 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	7.7% 2/26 • Number of events 2 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	1.9% 1/52 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	3.8% 1/26 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	0.00% 0/52 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	3.8% 1/26 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	1.9% 1/52 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	3.8% 1/26 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	1.9% 1/52 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/26 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Nervous system disorders Dizziness	0.00% 0/52 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	3.8% 1/26 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Nervous system disorders Nervous system disorders - Other, specify	0.00% 0/52 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	3.8% 1/26 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Nervous system disorders Seizure	1.9% 1/52 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/26 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Nervous system disorders Stroke	1.9% 1/52 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/26 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Nervous system disorders Syncope	0.00% 0/52 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	3.8% 1/26 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Psychiatric disorders Confusion	0.00% 0/52 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	7.7% 2/26 • Number of events 2 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Renal and urinary disorders Urinary tract obstruction	0.00% 0/52 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/26 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	8.3% 1/12 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/52 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	3.8% 1/26 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.9% 1/52 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	3.8% 1/26 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/52 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/26 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	8.3% 1/12 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Vascular disorders Hypotension	0.00% 0/52 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	3.8% 1/26 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Vascular disorders Thromboembolic event	1.9% 1/52 • Number of events 1 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	7.7% 2/26 • Number of events 2 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.	0.00% 0/12 The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.