Trial Outcomes & Findings for PEG-Interferon Alfa-2b in Treating Patients With Stage IV Melanoma (NCT NCT00049530)

Last Updated: 2023-06-29

Results Overview

The primary endpoint was the suppression of plasma b-FGF level with low dose peginterferon alfa-2b. A clinically important reduction of plasma b-FGF levels was determined to be a level less than or equal to 7.5 pg/mL. A patient was considered to have a suppressed plasma b-FGF level, if the patient experienced the clinically significant reduction (less than or equal to 7.5 pg/mL) of plasma b-FGF levels for two consecutive determinations which were at least three weeks apart. This was considered as a b-FGF response.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

32 participants

Primary outcome timeframe

assessed every 3 weeks until the suppression of plasma b-FGF level to normal, then every 6 weeks until the completion of 12 months of treatment, and upon treatment discontinuation

Results posted on

2023-06-29

Participant Flow

This study was activated on September 5, 2003, accrued its first patient on January 13, 2004, and patient accrual was terminated on June 15, 2011. A total of 32 patients were enrolled through ECOG member institutions. The study was suspended three times during the accrual period (February 2005, November 2006, January 2009) due to unavailability of ELISA kits to measure fibroblast growth factor.

This study involves a pre-registration and a registration. In the pre-registration phase, plasma samples must be submitted for determinations of b-FGF status by central analysis. Only patients determined to have an elevated b-FGF level (\>15 pg/mL) by central review are eligible for registration.

Participant milestones

Participant milestones
Measure	PEG-interferon Alfa-2b Patients receive PEG-interferon alfa-2b subcutaneously (SC) once weekly. Treatment continues until basic fibroblast growth factor level is suppressed to normal or until a maximum weekly dose is reached. If there is disease progression, patients then discontinue treatment. If there is no disease progression, patients receive PEG-interferon alfa-2b SC weekly for up to 1 year in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	32
Overall Study Eligible and Treated	29
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	32

Reasons for withdrawal

Reasons for withdrawal
Measure	PEG-interferon Alfa-2b Patients receive PEG-interferon alfa-2b subcutaneously (SC) once weekly. Treatment continues until basic fibroblast growth factor level is suppressed to normal or until a maximum weekly dose is reached. If there is disease progression, patients then discontinue treatment. If there is no disease progression, patients receive PEG-interferon alfa-2b SC weekly for up to 1 year in the absence of disease progression or unacceptable toxicity.
Overall Study Lack of Efficacy	25
Overall Study Adverse Event	2
Overall Study Death	1
Overall Study symptomatic deterioration	1
Overall Study ineligible	3

Baseline Characteristics

PEG-Interferon Alfa-2b in Treating Patients With Stage IV Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PEG-Interferon Alfa-2b n=29 Participants Patients receive PEG-interferon alfa-2b subcutaneously (SC) once weekly. Treatment continues until basic fibroblast growth factor level is suppressed to normal or until a maximum weekly dose is reached. If there is disease progression, patients then discontinue treatment. If there is no disease progression, patients receive PEG-interferon alfa-2b SC weekly for up to 1 year in the absence of disease progression or unacceptable toxicity.
Age, Continuous	64 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants
Region of Enrollment United States	32 participants n=5 Participants

PRIMARY outcome

Timeframe: assessed every 3 weeks until the suppression of plasma b-FGF level to normal, then every 6 weeks until the completion of 12 months of treatment, and upon treatment discontinuation

Population: eligible and treated patients

Outcome measures

Outcome measures
Measure	PEG-interferon Alfa-2b n=29 Participants Patients receive PEG-interferon alfa-2b subcutaneously (SC) once weekly. Treatment continues until basic fibroblast growth factor level is suppressed to normal or until a maximum weekly dose is reached. If there is disease progression, patients then discontinue treatment. If there is no disease progression, patients receive PEG-interferon alfa-2b SC weekly for up to 1 year in the absence of disease progression or unacceptable toxicity.
Plasma b-FGF Level Response	34.5 percentage of participants Interval 17.9 to 54.3

SECONDARY outcome

Timeframe: assessed every 9 weeks until suppression of plasma b-FGF level to normal, every 12 weeks until the completion of 12 months of treatment, >= 4 weeks after documented response. After off treatment, every 3 months if <2 years, and every 6 months if 2-3 years

Population: eligible and treated patients

Objective tumor response was assessed using RECIST (Response Evaluation Criteria in Solid Tumors) 1.0 criteria. Per RECIST criteria, complete response (CR) = disappearance of all target and non-target lesions. Partial response (PR)= \>=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. Progression is defined as at least 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. Stable disease (SD) = did not meet criteria for response or progression. Non-progression rate = CR + PR + SD.

Outcome measures

Outcome measures
Measure	PEG-interferon Alfa-2b n=29 Participants Patients receive PEG-interferon alfa-2b subcutaneously (SC) once weekly. Treatment continues until basic fibroblast growth factor level is suppressed to normal or until a maximum weekly dose is reached. If there is disease progression, patients then discontinue treatment. If there is no disease progression, patients receive PEG-interferon alfa-2b SC weekly for up to 1 year in the absence of disease progression or unacceptable toxicity.
Non-progression Rate (Clinical Response to Peginterferon Alfa-2b)	24.1 percentage of participants Interval 10.3 to 43.5

SECONDARY outcome

Population: eligible and treated patients

Progression free survival (PFS) was defined as the time from registration to disease progression, or censored at last known date of non progressive disease.

Outcome measures

Outcome measures
Measure	PEG-interferon Alfa-2b n=29 Participants Patients receive PEG-interferon alfa-2b subcutaneously (SC) once weekly. Treatment continues until basic fibroblast growth factor level is suppressed to normal or until a maximum weekly dose is reached. If there is disease progression, patients then discontinue treatment. If there is no disease progression, patients receive PEG-interferon alfa-2b SC weekly for up to 1 year in the absence of disease progression or unacceptable toxicity.
Progression Free Survival	2 months Interval 1.8 to 2.3

SECONDARY outcome

Timeframe: assessed every 3 months if <2 years, and every 6 months if 2-3 years

Population: eligible and treated

Overall survival (OS) time was defined as the time from registration to death from any cause, or censored at last known date of survival.

Outcome measures

Outcome measures
Measure	PEG-interferon Alfa-2b n=29 Participants Patients receive PEG-interferon alfa-2b subcutaneously (SC) once weekly. Treatment continues until basic fibroblast growth factor level is suppressed to normal or until a maximum weekly dose is reached. If there is disease progression, patients then discontinue treatment. If there is no disease progression, patients receive PEG-interferon alfa-2b SC weekly for up to 1 year in the absence of disease progression or unacceptable toxicity.
Overall Survival	9.7 months Interval 4.4 to 12.5

Adverse Events

PEG-Interferon Alfa-2b

Serious events: 13 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	PEG-Interferon Alfa-2b n=32 participants at risk Patients receive PEG-interferon alfa-2b subcutaneously (SC) once weekly. Treatment continues until basic fibroblast growth factor level is suppressed to normal or until a maximum weekly dose is reached. If there is disease progression, patients then discontinue treatment. If there is no disease progression, patients receive PEG-interferon alfa-2b SC weekly for up to 1 year in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	3.1% 1/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Investigations White blood cell decreased	3.1% 1/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Investigations Neutrophil count decreased	3.1% 1/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Vascular disorders Hypotension	3.1% 1/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
General disorders Fatigue	21.9% 7/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
General disorders Chills	3.1% 1/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
General disorders General disorders and administration sit	3.1% 1/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Gastrointestinal disorders Constipation	3.1% 1/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Gastrointestinal disorders Nausea	9.4% 3/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Gastrointestinal disorders Vomiting	3.1% 1/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Gastrointestinal disorders Gastrointestinal disorders - Other, spec	3.1% 1/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Investigations Alanine aminotransferase increased	3.1% 1/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Infections and infestations Infections w/o neutropenia	6.2% 2/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Psychiatric disorders Confusion	3.1% 1/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Nervous system disorders Dizziness	3.1% 1/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Psychiatric disorders Depression	3.1% 1/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Nervous system disorders Tremor	3.1% 1/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Musculoskeletal and connective tissue disorders Myalgia	3.1% 1/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
General disorders Pain	3.1% 1/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).

Other adverse events

Other adverse events
Measure	PEG-Interferon Alfa-2b n=32 participants at risk Patients receive PEG-interferon alfa-2b subcutaneously (SC) once weekly. Treatment continues until basic fibroblast growth factor level is suppressed to normal or until a maximum weekly dose is reached. If there is disease progression, patients then discontinue treatment. If there is no disease progression, patients receive PEG-interferon alfa-2b SC weekly for up to 1 year in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	46.9% 15/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Investigations White blood cell decreased	37.5% 12/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Investigations Neutrophil count decreased	37.5% 12/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Investigations Platelet count decreased	18.8% 6/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
General disorders Fatigue	75.0% 24/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
General disorders Fever	34.4% 11/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
General disorders Chills	18.8% 6/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Investigations Weight loss	21.9% 7/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Skin and subcutaneous tissue disorders Alopecia	6.2% 2/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Skin and subcutaneous tissue disorders Dry skin	6.2% 2/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
General disorders Injection site reaction	25.0% 8/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Skin and subcutaneous tissue disorders Pruritus	9.4% 3/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Skin and subcutaneous tissue disorders Rash maculo-papular	12.5% 4/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders -	6.2% 2/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Metabolism and nutrition disorders Anorexia	46.9% 15/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Gastrointestinal disorders Constipation	12.5% 4/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Metabolism and nutrition disorders Dehydration	6.2% 2/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Gastrointestinal disorders Nausea	40.6% 13/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Nervous system disorders Dysgeusia	6.2% 2/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Gastrointestinal disorders Vomiting	15.6% 5/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Gastrointestinal disorders Diarrhea	12.5% 4/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Investigations Blood bilirubin increased	6.2% 2/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Metabolism and nutrition disorders Hypoalbuminemia	6.2% 2/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Investigations Alanine aminotransferase increased	31.2% 10/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Nervous system disorders Dizziness	18.8% 6/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Psychiatric disorders Insomnia	12.5% 4/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Psychiatric disorders Anxiety	18.8% 6/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Psychiatric disorders Depression	15.6% 5/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Nervous system disorders Nervous system disorders - Other, specif	6.2% 2/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Nervous system disorders Tremor	6.2% 2/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Nervous system disorders Headache	15.6% 5/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Musculoskeletal and connective tissue disorders Myalgia	25.0% 8/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Respiratory, thoracic and mediastinal disorders Dyspnea	6.2% 2/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
Investigations Creatinine increased	12.5% 4/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).
General disorders General disorders and administration sit	6.2% 2/32 • Assessed every 3 weeks in induction phase, every 6 weeks in maintenance phase, and for 30 days after the end of treatment, up to 3 years. Adverse events occurred within 30 days after the end of treatment were reported in the Adverse Event Form for the last cycle. Long term grade 3 or higher adverse event which has not been previously reported were also included in the reporting (assessed every 3 months if patient is \<2 years from study entry and every 6 months if 2-3 years).

Additional Information

Study Statistician

ECOG Statistical Office

Phone: 617-632-3012

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place