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

Study Overview
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Brief Summary
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RATIONALE: Interferon alfa may interfere with the growth of cancer cells. Interleukin-2 may stimulate a person's white blood cells to kill melanoma cells. It is not yet known whether interferon alfa plus combination chemotherapy and interleukin-2 is more effective than interferon alfa alone in treating patients with melanoma. PURPOSE: Randomized phase III trial to compare the effectiveness of interferon alfa with or without combination chemotherapy plus interleukin-2 in treating patients with melanoma.

Detailed Description
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OBJECTIVES: Compare the efficacy of postoperative adjuvant therapy with interferon alfa-2b (IFN-A) administered subcutaneously with or without IV induction vs concurrent biochemotherapy including cisplatin, vinblastine, DTIC, IFN-A and IL-2 and in melanoma patients with regional lymph node metastases that have been surgically resected. Determine the relative toxic effects associated with adjuvant therapy with IFN-A and concurrent biochemotherapy including cisplatin, vinblastine, DTIC, IFN-A, and IL-2 and their effect on the quality of life. Determine the prognostic value of detection of melanoma cells in the peripheral blood using RT/PCR for tyrosinase mRNA. OUTLINE: This is a randomized study. All patients are stratified according to prognostic factors. Patients are randomly allocated to 1 of 2 treatment options. Treatment 1 uses interferon alfa-2b (IFN-A) therapy, and treatment 2 includes adjuvant biochemotherapy. Patients who are randomized to IFN-A will be further stratified and randomized to one of two interferon schedules. Schedule A: IV IFN-A induction 5 times a week for 4 weeks followed by subcutaneous IFN-A maintenance 3 times a week for 48 weeks. Schedule B: Subcutaneous IFN-A 3 times a week for 52 weeks. Adjuvant biochemotherapy begins immediately after registration on the study. Cisplatin is given IV on days 1-4; vinblastine is given IVPB on days 1-4; dacarbazine (DTIC) is given IVPB on day 1; IFN-A is given subcutaneously on days 1-5; IL-2 is given by continuous infusion for a total of 96 hours on days 1-4. Each course of therapy is repeated every 21 days for 4 courses. Patients receiving adjuvant radiotherapy will start adjuvant systemic therapy within 8 weeks from lymphadenectomy and a week after completion of and recovery from radiotherapy. PROJECTED ACCRUAL: A total of 200 patients (100 patients in each arm) will be entered.

Official Title
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Adjuvant Therapy for Melanoma Patients With Regional Lymph Node Metastases With Interferon Alfa-2B vs. Biochemotherapy Using Cisplatin + Vinblastine + DTIC + Interferon Plus IL-2

Conditions
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Melanoma, Skin Cancer

Intervention / Treatment
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* Biological: Aldesleukin (IL-2)
* Biological: Recombinant Interferon Alfa (IFN-A)
* Drug: Cisplatin
* Drug: Dacarbazine
* Drug: Vinblastine
* Procedure: Adjuvant Therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically diagnosed malignant melanoma with regional lymph node metastases Undergone complete lymph node dissection and free of any residual tumor No greater than 90 days from diagnosis of regional lymph nodes metastases No distant or resected in-transit metastases PATIENT CHARACTERISTICS: Age: 10 to 66 66 to 70 if in excellent physical condition Performance status: 0-2 Life expectancy: At least 12 months Hematopoietic: Hemoglobin greater than 10 g/dL WBC greater than 3,000/mm^3 Platelet count greater than 100,000/mm^3 Hepatic: Bilirubin no greater than 1.2 mg/dL Renal: Creatinine no greater than 1.5 mg/dL Other: No serious intercurrent illness that would compromise tolerance of therapy and long term survival Must be able to participate in follow up for minimum of 5 years No second malignancy except: In situ cervical cancer Basal or squamous skin cancer Must be able to physically and emotionally tolerate biochemotherapy No history of pulmonary or cardiac dysfunction, e.g., cardiac rhythm disturbance, congestive heart failure, coronary bypass, or impaired cardiac ejection fraction PRIOR CONCURRENT THERAPY: Biologic therapy: No prior immunotherapy with interferon or IL-2 No concurrent immunomodulators Chemotherapy: No prior chemotherapy Endocrine therapy: No concurrent steroids Radiotherapy: Prior adjuvant local radiotherapy allowed for head and neck Surgery: No greater than 8 weeks after definitive surgery for lymph node metastases Other: No concurrent nonsteroid anti-inflammatory drugs, or other prostaglandin synthetase inhibitors

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IFN-A Therapy Schedule A<br>Schedule A: IV Interferon alfa-2b (IFN-A) induction 5 times a week for 4 weeks followed by subcutaneous IFN-A maintenance 3 times a week for 48 weeks. | Biological: Recombinant Interferon Alfa (IFN-A)<br>* IFN-A Therapy Groups: Schedule A: IV IFN-A induction 5 times a week for 4 weeks followed by subcutaneous IFN-A maintenance 3 times a week for 48 weeks. Schedule B: Subcutaneous IFN-A 3 times a week for 52 weeks Adjuvant Biochemotherapy Group: IFN-A is given subcutaneously on days 1-5<br>* Other names: IFN-A;|
| Experimental: IFN-A Therapy Schedule B<br>Schedule B: Subcutaneous IFN-A 3 times a week for 52 weeks. | Biological: Recombinant Interferon Alfa (IFN-A)<br>* IFN-A Therapy Groups: Schedule A: IV IFN-A induction 5 times a week for 4 weeks followed by subcutaneous IFN-A maintenance 3 times a week for 48 weeks. Schedule B: Subcutaneous IFN-A 3 times a week for 52 weeks Adjuvant Biochemotherapy Group: IFN-A is given subcutaneously on days 1-5<br>* Other names: IFN-A;|
| Experimental: Adjuvant Biochemotherapy<br>Cisplatin IV Days 1-4; Vinblastine IVPB Days 1-4; Dacarbazine (DTIC) IVPB on Day 1; IFN-A is given subcutaneously on days 1-5; IL-2 continuous infusion for 96 hours on Days 1-4. Each course repeated every 21 days for 4 courses. | Biological: Aldesleukin (IL-2)<br>* Infusion for a total of 96 hours on days 1-4<br>* Other names: Proleukin;Biological: Recombinant Interferon Alfa (IFN-A)<br>* IFN-A Therapy Groups: Schedule A: IV IFN-A induction 5 times a week for 4 weeks followed by subcutaneous IFN-A maintenance 3 times a week for 48 weeks. Schedule B: Subcutaneous IFN-A 3 times a week for 52 weeks Adjuvant Biochemotherapy Group: IFN-A is given subcutaneously on days 1-5<br>* Other names: IFN-A;Drug: Cisplatin<br>* IV Days 1-4<br>* Other names: Platinol-AQ;Drug: Dacarbazine<br>* IVPB on day 1<br>* Other names: DTIC;Drug: Vinblastine<br>* IVPB on days 1-4<br>* Other names: Velban;Procedure: Adjuvant Therapy<br>* Patients receiving adjuvant radiotherapy will start adjuvant systemic therapy within 8 weeks from lymphadenectomy and a week after completion of and recovery from radiotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effectiveness of Interferon Alfa with/without Combination Chemotherapy + Interleukin-2 for Melanoma |  | 1 year | 

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