Trial Outcomes & Findings for A Study of Bevacizumab (Avastin) in Combination With Dacarbazine in Participants With Unresectable/Metastatic Melanoma (NCT NCT01164007)

NCT ID: NCT01164007

Last Updated: 2017-04-21

Results Overview

Tumor assessments were performed using RECIST. CR was defined as disappearance of all target and non-target lesions with normalization of tumor markers. PR was defined as greater than or equal to (≥) 30 percent (%) decrease in sum of longest diameter (LD) of target lesions in reference to sum of LD at Baseline. Both were to be confirmed at a follow-up visit at least 4 weeks from the initial assessment of CR or PR. The percentage of participants with a best overall response of CR or PR during the study was reported.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 40 participants
• Primary outcome timeframe: Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months)
• Results posted on: 2017-04-21

Participant Flow

Participant milestones

Measure	Dacarbazine + Bevacizumab Participants with unresectable/metastatic melanoma not previously treated with chemotherapy for metastatic disease received dacarbazine as 800 milligrams per square meter (mg/m\^2) via intravenous (IV) infusion on Day 1 and bevacizumab as 10 milligrams per kilogram (mg/kg) via IV infusion on Days 1 and 14 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, participant withdrawal, or physician decision to discontinue.
Overall Study STARTED	40
Overall Study Treated	37
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	40

Reasons for withdrawal

Measure	Dacarbazine + Bevacizumab Participants with unresectable/metastatic melanoma not previously treated with chemotherapy for metastatic disease received dacarbazine as 800 milligrams per square meter (mg/m\^2) via intravenous (IV) infusion on Day 1 and bevacizumab as 10 milligrams per kilogram (mg/kg) via IV infusion on Days 1 and 14 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, participant withdrawal, or physician decision to discontinue.
Overall Study Adverse Event	5
Overall Study Progression of Disease	30
Overall Study Protocol Violation	1
Overall Study Withdrawal by Subject	1
Overall Study Medical Decision	3

Baseline Characteristics

A Study of Bevacizumab (Avastin) in Combination With Dacarbazine in Participants With Unresectable/Metastatic Melanoma

Baseline characteristics by cohort

Measure	Dacarbazine + Bevacizumab n=37 Participants Participants with unresectable/metastatic melanoma not previously treated with chemotherapy for metastatic disease received dacarbazine as 800 mg/m\^2 via IV infusion on Day 1 and bevacizumab as 10 mg/kg via IV infusion on Days 1 and 14 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, participant withdrawal, or physician decision to discontinue.
Age, Continuous	54.16 years STANDARD_DEVIATION 13.11 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months)

Population: Intent-to-Treat (ITT) Population: All participants who signed the ICF, were assigned a study identifier, and received at least one dose of study medications.

Tumor assessments were performed using RECIST. CR was defined as disappearance of all target and non-target lesions with normalization of tumor markers. PR was defined as greater than or equal to (≥) 30 percent (%) decrease in sum of longest diameter (LD) of target lesions in reference to sum of LD at Baseline. Both were to be confirmed at a follow-up visit at least 4 weeks from the initial assessment of CR or PR. The percentage of participants with a best overall response of CR or PR during the study was reported.

Outcome measures

Measure

Dacarbazine + Bevacizumab n=37 Participants Participants with unresectable/metastatic melanoma not previously treated with chemotherapy for metastatic disease received dacarbazine as 800 mg/m\^2 via IV infusion on Day 1 and bevacizumab as 10 mg/kg via IV infusion on Days 1 and 14 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, participant withdrawal, or physician decision to discontinue.

Percentage of Participants With Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST)

18.92 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of participants with a previous assessment of CR or PR.

Tumor assessments were performed using RECIST. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum on study or the appearance of new lesion(s). CR was defined as disappearance of all target and non-target lesions with normalization of tumor markers. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. The percentage of participants who died or demonstrated disease progression among those with a previous assessment of CR or PR was reported.

Outcome measures

Measure

Dacarbazine + Bevacizumab n=7 Participants Participants with unresectable/metastatic melanoma not previously treated with chemotherapy for metastatic disease received dacarbazine as 800 mg/m\^2 via IV infusion on Day 1 and bevacizumab as 10 mg/kg via IV infusion on Days 1 and 14 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, participant withdrawal, or physician decision to discontinue.

Percentage of Participants With Death or Disease Progression Following a Previous Assessment of CR or PR According to RECIST

57.14 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of participants with a previous assessment of CR or PR.

Tumor assessments were performed using RECIST. DOR was defined as the time from first assessment of CR or PR to the time of death or disease progression, whichever occurred first. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum on study or the appearance of new lesion(s). CR was defined as disappearance of all target and non-target lesions with normalization of tumor markers. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. DOR was estimated by Kaplan-Meier methodology and expressed in months.

Outcome measures

Measure

Dacarbazine + Bevacizumab n=7 Participants Participants with unresectable/metastatic melanoma not previously treated with chemotherapy for metastatic disease received dacarbazine as 800 mg/m\^2 via IV infusion on Day 1 and bevacizumab as 10 mg/kg via IV infusion on Days 1 and 14 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, participant withdrawal, or physician decision to discontinue.

Duration of Response (DOR) With CR or PR According to RECIST

16.89 months Interval 5.77 to The upper limit could not be reached because of a high number of censored participants.

SECONDARY outcome

Timeframe: Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of participants with a previous assessment of CR, PR, or SD.

Tumor assessments were performed using RECIST. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum on study or the appearance of new lesion(s). CR was defined as disappearance of all target and non-target lesions with normalization of tumor markers. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for disease progression, using smallest sum of LD on study as reference. The percentage of participants who died or demonstrated disease progression among those with a previous assessment of CR, PR, or SD was reported.

Outcome measures

Measure

Dacarbazine + Bevacizumab n=18 Participants Participants with unresectable/metastatic melanoma not previously treated with chemotherapy for metastatic disease received dacarbazine as 800 mg/m\^2 via IV infusion on Day 1 and bevacizumab as 10 mg/kg via IV infusion on Days 1 and 14 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, participant withdrawal, or physician decision to discontinue.

Percentage of Participants With Death or Disease Progression Following a Previous Assessment of CR, PR, or Stable Disease (SD) According to RECIST

72.22 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of participants with a previous assessment of CR, PR, or SD.

Tumor assessments were performed using RECIST. DOR was defined as the time from first assessment of CR, PR, or SD to the time of death or disease progression, whichever occurred first. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum on study or the appearance of new lesion(s). CR was defined as disappearance of all target and non-target lesions with normalization of tumor markers. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for disease progression, using smallest sum of LD on study as reference. DOR was estimated by Kaplan-Meier methodology and expressed in months.

Outcome measures

Measure

Dacarbazine + Bevacizumab n=18 Participants Participants with unresectable/metastatic melanoma not previously treated with chemotherapy for metastatic disease received dacarbazine as 800 mg/m\^2 via IV infusion on Day 1 and bevacizumab as 10 mg/kg via IV infusion on Days 1 and 14 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, participant withdrawal, or physician decision to discontinue.

DOR With CR, PR, or SD According to RECIST

12.52 months Interval 5.61 to 17.7

SECONDARY outcome

Timeframe: Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months)

Population: ITT Population

Tumor assessments were performed using RECIST. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum on study or the appearance of new lesion(s). The percentage of participants who died or demonstrated disease progression was reported.

Outcome measures

Measure

Dacarbazine + Bevacizumab n=37 Participants Participants with unresectable/metastatic melanoma not previously treated with chemotherapy for metastatic disease received dacarbazine as 800 mg/m\^2 via IV infusion on Day 1 and bevacizumab as 10 mg/kg via IV infusion on Days 1 and 14 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, participant withdrawal, or physician decision to discontinue.

Percentage of Participants With Death or Disease Progression According to RECIST

81.08 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months)

Population: ITT Population

Tumor assessments were performed using RECIST. TTP was defined as the time from Baseline visit to time of death or disease progression, whichever occurred first. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum on study or the appearance of new lesion(s). TTP was estimated by Kaplan-Meier methodology and expressed in months.

Outcome measures

Measure

Dacarbazine + Bevacizumab n=37 Participants Participants with unresectable/metastatic melanoma not previously treated with chemotherapy for metastatic disease received dacarbazine as 800 mg/m\^2 via IV infusion on Day 1 and bevacizumab as 10 mg/kg via IV infusion on Days 1 and 14 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, participant withdrawal, or physician decision to discontinue.

Time to Progression (TTP) According to RECIST

5.48 months Interval 2.95 to 10.92

SECONDARY outcome

Timeframe: Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months)

Population: ITT Population

The percentage of participants who discontinued treatment as a result of death, adverse event, disease progression, loss to follow-up, non-compliance, or consent withdrawal was reported. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum on study or the appearance of new lesion(s).

Outcome measures

Measure

Dacarbazine + Bevacizumab n=37 Participants Participants with unresectable/metastatic melanoma not previously treated with chemotherapy for metastatic disease received dacarbazine as 800 mg/m\^2 via IV infusion on Day 1 and bevacizumab as 10 mg/kg via IV infusion on Days 1 and 14 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, participant withdrawal, or physician decision to discontinue.

Percentage of Participants Who Discontinued Treatment

91.89 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months)

Population: ITT Population

TTF was defined as the time from start of treatment to the time of treatment discontinuation as a result of death, adverse event, disease progression, loss to follow-up, non-compliance, or consent withdrawal was reported. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum on study or the appearance of new lesion(s). TTF was estimated by Kaplan-Meier methodology and expressed in months.

Outcome measures

Measure

Dacarbazine + Bevacizumab n=37 Participants Participants with unresectable/metastatic melanoma not previously treated with chemotherapy for metastatic disease received dacarbazine as 800 mg/m\^2 via IV infusion on Day 1 and bevacizumab as 10 mg/kg via IV infusion on Days 1 and 14 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, participant withdrawal, or physician decision to discontinue.

Time to Treatment Failure (TTF)

3.05 months Interval 2.56 to 8.75

SECONDARY outcome

Timeframe: Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months)

Population: ITT Population

The percentage of participants who died from any cause was reported.

Outcome measures

Measure

Dacarbazine + Bevacizumab n=37 Participants Participants with unresectable/metastatic melanoma not previously treated with chemotherapy for metastatic disease received dacarbazine as 800 mg/m\^2 via IV infusion on Day 1 and bevacizumab as 10 mg/kg via IV infusion on Days 1 and 14 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, participant withdrawal, or physician decision to discontinue.

Percentage of Participants Who Died

81.08 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months)

Population: ITT Population

OS was defined as the time from Baseline visit to the time of death from any cause. OS was estimated by Kaplan-Meier methodology and expressed in months.

Outcome measures

Measure

Dacarbazine + Bevacizumab n=37 Participants Participants with unresectable/metastatic melanoma not previously treated with chemotherapy for metastatic disease received dacarbazine as 800 mg/m\^2 via IV infusion on Day 1 and bevacizumab as 10 mg/kg via IV infusion on Days 1 and 14 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, participant withdrawal, or physician decision to discontinue.

Overall Survival (OS)

11.41 months Interval 6.46 to 25.11

Adverse Events

Dacarbazine + Bevacizumab

Serious events: 5 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Measure	Dacarbazine + Bevacizumab n=37 participants at risk Participants with unresectable/metastatic melanoma not previously treated with chemotherapy for metastatic disease received dacarbazine as 800 mg/m\^2 via IV infusion on Day 1 and bevacizumab as 10 mg/kg via IV infusion on Days 1 and 14 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, participant withdrawal, or physician decision to discontinue.
General disorders Pyrexia	2.7% 1/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Cardiac disorders Cardiac failure	2.7% 1/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Cardiac disorders Pericardial effusion	2.7% 1/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.7% 1/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Injury, poisoning and procedural complications Femur fracture	2.7% 1/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Immune system disorders Drug hypersensitivity	2.7% 1/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Infections and infestations Influenza	2.7% 1/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population

Other adverse events

Measure	Dacarbazine + Bevacizumab n=37 participants at risk Participants with unresectable/metastatic melanoma not previously treated with chemotherapy for metastatic disease received dacarbazine as 800 mg/m\^2 via IV infusion on Day 1 and bevacizumab as 10 mg/kg via IV infusion on Days 1 and 14 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, participant withdrawal, or physician decision to discontinue.
Blood and lymphatic system disorders Anaemia	10.8% 4/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Blood and lymphatic system disorders Leukopenia	10.8% 4/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Blood and lymphatic system disorders Neutropenia	8.1% 3/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Blood and lymphatic system disorders Thrombocytopenia	13.5% 5/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Eye disorders Conjunctivitis	10.8% 4/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Gastrointestinal disorders Abdominal pain	16.2% 6/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Gastrointestinal disorders Abdominal pain upper	21.6% 8/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Gastrointestinal disorders Constipation	40.5% 15/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Gastrointestinal disorders Diarrhoea	21.6% 8/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Gastrointestinal disorders Dyspepsia	8.1% 3/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Gastrointestinal disorders Nausea	24.3% 9/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Gastrointestinal disorders Toothache	5.4% 2/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Gastrointestinal disorders Vomiting	16.2% 6/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
General disorders Asthenia	27.0% 10/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
General disorders General physical health deterioration	5.4% 2/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
General disorders Mucosal inflammation	21.6% 8/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
General disorders Pyrexia	10.8% 4/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Infections and infestations Influenza	10.8% 4/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Infections and infestations Rhinitis	10.8% 4/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Metabolism and nutrition disorders Hypokalaemia	5.4% 2/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Musculoskeletal and connective tissue disorders Arthralgia	8.1% 3/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Musculoskeletal and connective tissue disorders Back pain	5.4% 2/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Musculoskeletal and connective tissue disorders Groin pain	5.4% 2/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.4% 2/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Musculoskeletal and connective tissue disorders Neck pain	5.4% 2/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Musculoskeletal and connective tissue disorders Pain in extremity	8.1% 3/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Nervous system disorders Headache	10.8% 4/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Nervous system disorders Migraine	5.4% 2/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Psychiatric disorders Insomnia	8.1% 3/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Renal and urinary disorders Proteinuria	10.8% 4/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Renal and urinary disorders Strangury	8.1% 3/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Respiratory, thoracic and mediastinal disorders Cough	18.9% 7/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Respiratory, thoracic and mediastinal disorders Dysphonia	5.4% 2/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.8% 4/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Respiratory, thoracic and mediastinal disorders Epistaxis	8.1% 3/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	10.8% 4/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Skin and subcutaneous tissue disorders Erythema	5.4% 2/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Skin and subcutaneous tissue disorders Pruritus	5.4% 2/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Skin and subcutaneous tissue disorders Rash	5.4% 2/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population
Vascular disorders Hypertension	18.9% 7/37 • Baseline up to approximately 6 years (assessed continuously on treatment) Safety Population

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER