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

Study Overview
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Brief Summary
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This study will assess the preliminary anti-tumor activity and safety profile of a combination of bevacizumab and dacarbazine in participants with unresectable/metastatic melanoma not previously treated with chemotherapy for metastatic disease.

Official Title
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Phase II Study of Dacarbazine With the Anti-Vascular Endothelial Growth Factor Antibody (Bevacizumab) in Patients With Unresectable/Metastatic Melanoma

Conditions
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Malignant Melanoma

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: Dacarbazine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed cutaneous malignant melanoma Clinical evidence of metastatic disease and/or unresectable regional lymphatic disease and/or extensive in transit recurrent disease Measurable and/or evaluable lesions according to RECIST Exclusion Criteria: Prior interferon alfa and/or cytokine therapy for metastatic disease Prior chemotherapy for metastatic disease Brain metastases Chronic daily treatment with high-dose aspirin (more than 325 milligrams per day) Other co-existing malignancies or malignancies diagnosed within the past 5 years with the exception of basal cell cancer or cervical cancer in situ

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dacarbazine + Bevacizumab<br>Participants with unresectable/metastatic melanoma not previously treated with chemotherapy for metastatic disease will receive dacarbazine and bevacizumab until disease progression, unacceptable toxicity, participant withdrawal, or physician decision to discontinue. | Drug: Bevacizumab<br>* Bevacizumab will be given as 10 milligrams per kilogram (mg/kg) via intravenous (IV) infusion on Days 1 and 14 of each 28-day cycle.<br>* Other names: Avastin;Drug: Dacarbazine<br>* Dacarbazine will be given as 800 milligrams per square meter (mg/m^2) via IV infusion on Day 1 of each 28-day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) | 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. | Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Death or Disease Progression Following a Previous Assessment of CR or PR According to RECIST | 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. | Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months) | 
| Duration of Response (DOR) With CR or PR According to RECIST | 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. | Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months) | 
| Percentage of Participants With Death or Disease Progression Following a Previous Assessment of CR, PR, or Stable Disease (SD) According to RECIST | 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. | Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months) | 
| DOR With CR, PR, or SD According to RECIST | 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. | Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months) | 
| Percentage of Participants With Death or Disease Progression According to RECIST | 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. | Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months) | 
| Time to Progression (TTP) According to RECIST | 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. | Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months) | 
| Percentage of Participants Who Discontinued Treatment | 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). | Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months) | 
| Time to Treatment Failure (TTF) | 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. | Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months) | 
| Percentage of Participants Who Died | The percentage of participants who died from any cause was reported. | Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months) | 
| Overall Survival (OS) | 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. | Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months) |