Combination Chemotherapy Plus Biological Therapy 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. Biological therapies use different ways to stimulate the immune system and stop cancer cell from growing. Combining more than one drug with different types of biological therapies may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus biological therapy in treating patients who have metastatic melanoma.

Detailed Description
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OBJECTIVES: Determine the toxicity of cisplatin and dacarbazine followed by sargramostim (GM-CSF), interferon alfa, and interleukin-2 in patients with metastatic melanoma. Determine the objective response rate, relapse free survival, and overall survival of these patients on this regimen. OUTLINE: Patients receive cisplatin IV over 1 hour and dacarbazine IV over 30-60 minutes sequentially on day 1, followed by sargramostim (GM-CSF) subcutaneously (SC) on days 2-7, interleukin-2 SC on days 8-14, and interferon alfa SC on days 8, 10, 12, and 14. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 8 weeks until disease progression, and then every 8-12 weeks thereafter. PROJECTED ACCRUAL: A total of 15-45 patients will be accrued for this study within 3 years.

Official Title
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Phase II Study of Outpatient CDDP and DTIC Followed by GM-CSF, IFN-a2b, and IL-2 in Patients With Advanced Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Drug: Cisplatin
* Drug: dacarbazine
* Drug: Granulocyte-macrophage colony-stimulating factor


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed metastatic melanoma Stage III with intransit metastases Stage IV No uncontrolled brain metastases by CT scan No clinically significant ascites or pleural effusions PATIENT CHARACTERISTICS: Age: Not specified Performance status: Karnofsky 70-100% Life expectancy: At least 10 weeks Hematopoietic: WBC at least 3,000/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 9.5 g/dL Hepatic: Bilirubin no greater than 2.0 mg/dL SGOT no greater than 4 times upper limit of normal Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 70 mL/min Cardiovascular: No clinically significant cardiac disease on EKG, echocardiogram, or MUGA scan Pulmonary: No clinically significant pulmonary disease on chest x-ray Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No significant thyroid dysfunction No concurrent severe infection No other medical or psychiatric condition that would interfere with compliance No second malignancy within the past 5 years, except: Localized nonmelanomatous skin cancer Carcinoma in situ of the cervix Grade 1 Ta bladder cancer Suspected hearing deficits must undergo audiologic testing PRIOR CONCURRENT THERAPY: Biologic therapy: No more than one prior immunotherapy regimen At least 4 weeks since prior immunotherapy Adjuvant interferon alfa before relapse allowed Chemotherapy: No more than one prior chemotherapy regimen At least 4 weeks since prior chemotherapy (6 weeks since nitrosoureas) No concurrent cyclophosphamide No other concurrent chemotherapy Endocrine therapy: No concurrent corticosteroids or cyclosporine A Radiotherapy: At least 2 weeks since prior radiotherapy Surgery: At least 3 weeks since major surgery Other: No concurrent immunosuppressive drugs No other concurrent investigational antineoplastic drugs Concurrent thyroid replacement therapy allowed
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: Arm A<br>CDDP (75 mg/m2) and DTIC (660 mg/m2) will be administered sequentially by intravenous infusion in day 1. Subsequently, GM-CSF (450 mg/ m2) will be administered SC days 2-7; IL-2 (11 MU daily) will be given SC days 8-14, and IFN-2b (9 MU) will be given SC days 8, 10, 12, and 14. | Drug: Cisplatin<br> <br> * Other names: CDDP;Drug: dacarbazine<br> <br> * Other names: DTIC;Drug: Granulocyte-macrophage colony-stimulating factor<br> <br> * Other names: GM-CSF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate |  | 2 years | 

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