Bevacizumab, Dacarbazine and Interferon-Alfa to Treat Metastatic Melanoma

Study Overview
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Brief Summary
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The purpose of this study is to determine whether combination therapy with bevacizumab (Avastin), dacarbazine and interferon-alfa-2a (Roferon-A) is effective in patients with locally advancing or metastatic melanoma.

Detailed Description
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Dacarbazine (DTIC) has been approved for treating metastatic melanoma in the 1970s, and after that numerous schedules and dacarbazine-based combinations have been studied in this disease. DTIC as a single agent gives a response rate of only 20%, but there have been efforts to improve this poor result by using DTIC in different combinations.Treatment of melanoma with combination chemotherapy and interferon-α (IFN-α) has given 50-60% response rates,but increase in the overall survival time has not been reached in controlled phase III studies. Thus, standard reference therapy in treatment of metastatic melanoma still is single dacarbazine or its combination with s.c. IFN-α. In addition, new studies with melanoma cells in vitro show that dacarbazine causes transcriptional up-regulation of vascular endothelial growth factor (VEGF), suggesting a potential clinical benefit of combination of DTIC and anti-VEGF therapy. IFN-α has been used in adjuvant therapy and in treatment of metastatic melanoma. IFN-α exerts its effects through antiproliferative, apoptosis-inducing and particularly antiangiogenic effects in addition to immunologic modulation. The purpose of this study is to determine whether combination therapy with bevacizumab (Avastin), dacarbazine and interferon-alfa-2a (Roferon-A) can increase progression-free survival and overall survival in patients with locally advancing or metastatic melanoma.

Official Title
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Bevacizumab, Dacarbazine and Interferon Alfa-2a Combination as a First-Line Therapy in Patients With Locally Advancing or Metastatic Melanoma

Conditions
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Metastatic Melanoma

Intervention / Treatment
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* Drug: Bevacizumab (Avastin)
* Drug: dacarbazine
* Drug: interferon-alfa-2a (Roferon-A)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically confirmed malignant melanoma either locally progressing inoperable or metastatic measurable/evaluable disease in accordance with RECIST criteria WHO performance status 0-2 normal organ function signed written informed consent Exclusion Criteria: unevaluable disease major surgery within 28 days prior to day 0 uncompleted radiotherapy CNS metastases serious non-healing wound or ulcer bleeding diathesis or coagulopathy uncontrolled hypertension clinically significant cardiovascular disease depression or psychosis, which needs medication ongoing treatment with aspirin (>325 mg/day) pregnancy any other serious or uncontrolled illness previous chemotherapy for metastatic melanoma

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Bevacizumab (Avastin)|nan|
|Drug: dacarbazine|nan|
|Drug: interferon-alfa-2a (Roferon-A)|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate according to RECIST criteria |  |  | 
| Progression-free survival |  |  | 
| Time to brain metastases |  |  | 
| Overall survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate safety of this combination after every two cycles |  |  | 
| Serum analysis of particular biochemical markers |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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melanoma, metastatic, bevacizumab