Combination Chemotherapy With or Without Interleukin-2 and Interferon Alfa in Treating Patients With Metastatic Melanoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interleukin-2 may stimulate a person's white blood cells to kill melanoma cells. Interferon alfa may interfere with the growth of tumor cells. It is not yet known whether combination chemotherapy plus interleukin-2 and interferon alfa is more effective than combination chemotherapy alone for metastatic melanoma. PURPOSE: Randomized phase III trial to compare combination chemotherapy with or without interleukin-2 and interferon alfa in treating patients who have metastatic melanoma that cannot be treated by surgery.

Detailed Description
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OBJECTIVES: Compare response rate, duration of response, and survival rate in patients with metastatic malignant melanoma treated with cisplatin, vinblastine, and dacarbazine with or without interleukin-2 and interferon alfa-2b. Determine the toxic effects of these regimens in this patient population. OUTLINE: This is a randomized study. Patients are stratified according to performance status (0 vs 1), prior interferon (yes vs no), and number of involved sites. Patients are randomized to one of two treatment arms. Arm I: Patients receive cisplatin IV over 30 minutes daily immediately followed by vinblastine IV on days 1-4. Patients also receive dacarbazine IV over 60 minutes on day 1 following vinblastine. Arm II: Patients receive treatment as in arm I. Patients also receive interleukin 2 (IL-2) IV continuously on days 1-4 and interferon alfa-2b subcutaneously (SC) daily before IL-2 on days 1-4 and after IL-2 on day 5, followed by filgrastim (G-CSF) (SC) daily on days 7-16. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients are followed at 6 weeks, every 3 months for 18 months, every 6 months for 18 months, and then annually for 2 years. PROJECTED ACCRUAL: A total of 482 patients will be accrued for this study within 3.5 years.

Official Title
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A Randomized Phase III Trial of Concurrent Biochemotherapy With Cisplatin, Vinblastine, Dacarbazine, IL-2 and Interferon A-2B Versus Cisplatin, Vinblastine, Dacarbazine Alone in Patients With Metastatic Malignant Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: aldesleukin
* Biological: filgrastim
* Biological: recombinant interferon alfa
* Drug: cisplatin
* Drug: dacarbazine
* Drug: vinblastine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed surgically incurable metastatic malignant melanoma Measurable disease No active brain metastases or edema No leptomeningeal disease No ocular melanoma PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 9 g/dL Hepatic: Bilirubin no greater than 1.5 mg/dL SGOT less than 3 times the upper limit of normal unless due to liver metastases Renal: Creatinine less than 1.5 mg/dL OR Creatinine clearance at least 75 mL/min Cardiovascular: No congestive heart failure No symptoms of coronary artery disease No serious cardiac arrhythmias No prior myocardial infarction on EKG Normal cardiac stress test required for the following: Over 50 years of age Abnormal EKG Prior history of cardiac disease Pulmonary: No symptomatic pulmonary disease FEV1 greater than 2.0 L OR at least 75% predicted if over 50 years of age or with history of pulmonary symptoms Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No significant infection HIV negative No other prior malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix No organ allografts No significant disease other than malignancy No seizure disorder PRIOR CONCURRENT THERAPY: Biologic therapy: No prior interleukin-2 therapy for metastatic disease At least 4 weeks since prior vaccine therapy At least 4 weeks since prior adjuvant immunotherapy Chemotherapy: No prior chemotherapy for disease Endocrine therapy: No concurrent corticosteroids Radiotherapy: No prior radiation therapy to measurable disease site unless disease is clearly progressive At least 4 weeks since prior radiation therapy for local control or palliation and recovered Surgery: Recovered from prior surgery Other: No prior systemic therapy for metastatic disease At least 3 months since definitive therapy for brain metastases

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: aldesleukin|nan|
|Biological: filgrastim|nan|
|Biological: recombinant interferon alfa|nan|
|Drug: cisplatin|nan|
|Drug: dacarbazine|nan|
|Drug: vinblastine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate (complete and partial response) |  |  | 
| Durable complete response rate |  |  | 
| Response duration |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV melanoma