Trial Outcomes & Findings for AMG 706 and Octreotide in Treating Patients With Low-Grade Neuroendocrine Tumors (NCT NCT00427349)

Last Updated: 2023-07-05

Results Overview

Four-month progression-free survival (PFS) rate is defined as number of patients who are still progression free at 4 months after study entry divided by number of eligible and treated patients enrolled to the study. Progression is evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s), or unequivocal progression of existing non-target lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

46 participants

Primary outcome timeframe

assessed every 4 weeks while on treatment and at three months post-treatment for participants treated for one cycle, up to month four

Results posted on

2023-07-05

Participant Flow

This study was activated on September 16, 2008, accrued its first patient on November 7, 2008, and closed on March 18, 2010 with 46 patients registered to the study from 10 ECOG-ACRIN affiliated institutions.

Participant milestones

Participant milestones
Measure	AMG 706+Octreotide Patients receive oral AMG 706 and octreotide acetate intramuscularly once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. AMG 706: AMG 706 was administered on a flat scale of mg/day and not by weight or body surface area (BSA). AMG 706 was provided as a 25 mg tablet; the daily dose was 125 mg administered as five 25 mg tablets in the AM. AMG 706 was taken daily without breaks in treatment. octreotide: One dose consisted of octreotide-LAR 30 mg administered IM on day 1 of each cycle. The first octreotide-LAR injection would correspond with the first day of AMG 706 and then on day 1 of subsequent cycles.
Overall Study STARTED	46
Overall Study Eligible	45
Overall Study Treated	45
Overall Study Eligible and Treated	44
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	46

Reasons for withdrawal

Reasons for withdrawal
Measure	AMG 706+Octreotide Patients receive oral AMG 706 and octreotide acetate intramuscularly once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. AMG 706: AMG 706 was administered on a flat scale of mg/day and not by weight or body surface area (BSA). AMG 706 was provided as a 25 mg tablet; the daily dose was 125 mg administered as five 25 mg tablets in the AM. AMG 706 was taken daily without breaks in treatment. octreotide: One dose consisted of octreotide-LAR 30 mg administered IM on day 1 of each cycle. The first octreotide-LAR injection would correspond with the first day of AMG 706 and then on day 1 of subsequent cycles.
Overall Study Lack of Efficacy	23
Overall Study Adverse Event	14
Overall Study Death	1
Overall Study Withdrawal by Subject	3
Overall Study Alternative therapy	1
Overall Study Other	2
Overall Study Ineligible	1
Overall Study Never started therapy	1

Baseline Characteristics

AMG 706 and Octreotide in Treating Patients With Low-Grade Neuroendocrine Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AMG 706+Octreotide n=44 Participants Patients receive oral AMG 706 and octreotide acetate intramuscularly once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. AMG 706: AMG 706 was administered on a flat scale of mg/day and not by weight or body surface area (BSA). AMG 706 was provided as a 25 mg tablet; the daily dose was 125 mg administered as five 25 mg tablets in the AM. AMG 706 was taken daily without breaks in treatment. octreotide: One dose consisted of octreotide-LAR 30 mg administered IM on day 1 of each cycle. The first octreotide-LAR injection would correspond with the first day of AMG 706 and then on day 1 of subsequent cycles.
Age, Continuous	65 years n=93 Participants
Sex: Female, Male Female	20 Participants n=93 Participants
Sex: Female, Male Male	24 Participants n=93 Participants
Region of Enrollment United States	44 participants n=93 Participants

PRIMARY outcome

Timeframe: assessed every 4 weeks while on treatment and at three months post-treatment for participants treated for one cycle, up to month four

Population: The analysis population includes all 44 eligible and treated patients. But 2 patients did not have disease assessment after study entry and are excluded from the analysis.

Outcome measures

Outcome measures
Measure	AMG 706+Octreotide n=42 Participants Patients receive oral AMG 706 and octreotide acetate intramuscularly once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. AMG 706: AMG 706 was administered on a flat scale of mg/day and not by weight or body surface area (BSA). AMG 706 was provided as a 25 mg tablet; the daily dose was 125 mg administered as five 25 mg tablets in the AM. AMG 706 was taken daily without breaks in treatment. octreotide: One dose consisted of octreotide-LAR 30 mg administered IM on day 1 of each cycle. The first octreotide-LAR injection would correspond with the first day of AMG 706 and then on day 1 of subsequent cycles.
Four-month Progression-free Survival Rate	78.5 percentage of participants Interval 65.6 to 88.3

SECONDARY outcome

Timeframe: assessed every 3 months if patient is < 2 years from study entry, then every 6 months up to 5 years

Population: All eligible and treated patients

Overall survival (OS) is defined as the time from registration until death (event), or censored at last date known alive. OS was estimated using the Kaplan-Meier method , with 95% confidence intervals calculated using Greenwood's formula

Outcome measures

Outcome measures
Measure	AMG 706+Octreotide n=44 Participants Patients receive oral AMG 706 and octreotide acetate intramuscularly once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. AMG 706: AMG 706 was administered on a flat scale of mg/day and not by weight or body surface area (BSA). AMG 706 was provided as a 25 mg tablet; the daily dose was 125 mg administered as five 25 mg tablets in the AM. AMG 706 was taken daily without breaks in treatment. octreotide: One dose consisted of octreotide-LAR 30 mg administered IM on day 1 of each cycle. The first octreotide-LAR injection would correspond with the first day of AMG 706 and then on day 1 of subsequent cycles.
Overall Survival	27.5 months Interval 14.6 to 45.1

SECONDARY outcome

Timeframe: assessed every 8 weeks while on treatment, and frequency of tumor measurements during follow-up were determined by the treating physician, assessed up to 5 years

Tumor response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Objective response rate is defined as number of patients with complete response (CR) or partial response (PR) divided by the total number of analyzable patients. CR is defined as complete disappearance of all tumor lesions, and partial response is defined as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter.

Outcome measures

Outcome measures
Measure	AMG 706+Octreotide n=44 Participants Patients receive oral AMG 706 and octreotide acetate intramuscularly once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. AMG 706: AMG 706 was administered on a flat scale of mg/day and not by weight or body surface area (BSA). AMG 706 was provided as a 25 mg tablet; the daily dose was 125 mg administered as five 25 mg tablets in the AM. AMG 706 was taken daily without breaks in treatment. octreotide: One dose consisted of octreotide-LAR 30 mg administered IM on day 1 of each cycle. The first octreotide-LAR injection would correspond with the first day of AMG 706 and then on day 1 of subsequent cycles.
Objective Response Rate	13.6 percentage of participants Interval 6.0 to 25.0

Adverse Events

MG 706+Octreotide

Serious events: 26 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	MG 706+Octreotide n=45 participants at risk AMG 706 was administered on a flat scale of mg/day and not by weight or body surface area (BSA). AMG 706 was provided as a 25 mg tablet; the daily dose was 125 mg administered as five 25 mg tablets in the AM. AMG 706 was taken daily without breaks in treatment. Each cycle was defined as 28 days. AMG 706 was started within 7 working days of registration, given on the same day as the octreotide-LAR.
Blood and lymphatic system disorders Anemia	4.4% 2/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Investigations Lymphocyte count decreased	2.2% 1/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Investigations Platelet count decreased	6.7% 3/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Investigations Electrocardiogram QT corrected interval	2.2% 1/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Vascular disorders Hypertension	26.7% 12/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	2.2% 1/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
General disorders Fatigue	13.3% 6/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Investigations Weight loss	2.2% 1/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Investigations INR increased	2.2% 1/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Metabolism and nutrition disorders Anorexia	4.4% 2/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Metabolism and nutrition disorders Dehydration	4.4% 2/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Gastrointestinal disorders Diarrhea	8.9% 4/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Gastrointestinal disorders Nausea	6.7% 3/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Gastrointestinal disorders Vomiting	4.4% 2/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Gastrointestinal disorders Intra-abdominal hemorrhage	2.2% 1/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Hepatobiliary disorders Cholecystitis	11.1% 5/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Infections and infestations Urinary tract infection	2.2% 1/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Infections and infestations Infections and infestations - blood	2.2% 1/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Investigations Alkaline phosphatase increased	4.4% 2/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Investigations Alanine aminotransferase increased	2.2% 1/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Investigations Aspartate aminotransferase increased	2.2% 1/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Investigations Blood bilirubin increased	2.2% 1/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Metabolism and nutrition disorders Hypocalcemia	2.2% 1/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Investigations Lipase increased	2.2% 1/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Metabolism and nutrition disorders Hypomagnesemia	2.2% 1/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Metabolism and nutrition disorders Hypokalemia	2.2% 1/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Nervous system disorders Ataxia	4.4% 2/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Psychiatric disorders Confusion	2.2% 1/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Nervous system disorders Dizziness	2.2% 1/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Gastrointestinal disorders Abdominal pain	8.9% 4/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Nervous system disorders Headache	4.4% 2/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Respiratory, thoracic and mediastinal disorders Dyspnea	2.2% 1/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Vascular disorders Thromboembolic event	2.2% 1/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.

Other adverse events

Other adverse events
Measure	MG 706+Octreotide n=45 participants at risk AMG 706 was administered on a flat scale of mg/day and not by weight or body surface area (BSA). AMG 706 was provided as a 25 mg tablet; the daily dose was 125 mg administered as five 25 mg tablets in the AM. AMG 706 was taken daily without breaks in treatment. Each cycle was defined as 28 days. AMG 706 was started within 7 working days of registration, given on the same day as the octreotide-LAR.
Blood and lymphatic system disorders Anemia	24.4% 11/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Investigations White blood cell decreased	24.4% 11/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Investigations Lymphocyte count decreased	15.6% 7/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Investigations Neutrophil count decreased	15.6% 7/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Investigations Platelet count decreased	28.9% 13/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Vascular disorders Hypertension	57.8% 26/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Vascular disorders Hypotension	6.7% 3/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Cardiac disorders Left ventricular systolic dysfunction	15.6% 7/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
General disorders Fatigue	64.4% 29/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Skin and subcutaneous tissue disorders Hyperhidrosis	6.7% 3/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Investigations Weight loss	46.7% 21/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Metabolism and nutrition disorders Anorexia	33.3% 15/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Gastrointestinal disorders Constipation	13.3% 6/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Gastrointestinal disorders Diarrhea	51.1% 23/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Gastrointestinal disorders Abdominal distension	17.8% 8/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Gastrointestinal disorders Dry mouth	6.7% 3/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Gastrointestinal disorders Flatulence	8.9% 4/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Gastrointestinal disorders Nausea	28.9% 13/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Gastrointestinal disorders Vomiting	20.0% 9/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
General disorders Edema limbs	6.7% 3/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Metabolism and nutrition disorders Hypoalbuminemia	11.1% 5/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Investigations Alkaline phosphatase increased	20.0% 9/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Investigations Alanine aminotransferase increased	8.9% 4/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Investigations Aspartate aminotransferase increased	26.7% 12/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Investigations Blood bilirubin increased	6.7% 3/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Investigations Creatinine increased	6.7% 3/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Metabolism and nutrition disorders Hyperglycemia	24.4% 11/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Metabolism and nutrition disorders Hypokalemia	8.9% 4/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Metabolism and nutrition disorders Hyponatremia	8.9% 4/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Nervous system disorders Dizziness	11.1% 5/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Nervous system disorders Peripheral sensory neuropathy	6.7% 3/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Gastrointestinal disorders Abdominal pain	20.0% 9/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Musculoskeletal and connective tissue disorders Back pain	6.7% 3/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Nervous system disorders Headache	35.6% 16/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Musculoskeletal and connective tissue disorders Myalgia	13.3% 6/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Respiratory, thoracic and mediastinal disorders Dyspnea	11.1% 5/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.
Respiratory, thoracic and mediastinal disorders Voice alteration	8.9% 4/45 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up forms at each follow-up visit.

Additional Information

Study Statistician

ECOG-ACRIN Statistical Office

Phone: 617-632-3012

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60