Chemotherapy With or Without Immunotherapy in Treating Patients With Stage III or Stage IV Melanoma

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Injecting allovectin-7 into a person's melanoma cells may make the body build an immune response that will kill tumor cells.

PURPOSE: Randomized phase III trial to compare the effectiveness of dacarbazine with or without immunotherapy in treating patients who have stage III or stage IV melanoma.

OBJECTIVES: I. Demonstrate either an improvement in the median time to disease progression by at least 2 months with no decrease in the rate of objective clinical response OR an improvement by at least 15% in the rate of objective clinical response with no decrease in the median time to disease progression in patients with stage III or IV melanoma receiving dacarbazine with Allovectin-7 when compared with patients receiving dacarbazine alone.

II. Determine the benefits, risks, and side effects of these regimens in this patient population.

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are stratified according to sex, age, and spread of disease (cutaneous or nodal vs visceral disease). Patients are randomized to one of two treatment arms.

Arm I: Patients receive dacarbazine IV over 1 hour on day 0. Arm II: Patients receive treatment as in arm I. Patients also receive Allovectin-7 intratumorally on days 3 and 10.

Patients with stable or responding disease may receive additional courses every 28 days.

Patients are followed every 4 months.

PROJECTED ACCRUAL:

A total of 280 patients (140 in each arm) will be accrued for this study.

Eligibility Criteria:
PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

* Histologically confirmed stage III or IV melanoma 1 or more metastatic tumors for which surgery is not deemed to be a curative option
* Dacarbazine is indicated as first line chemotherapy
* At least 1 measurable tumor at least 1 cm2 but no greater than 100 cm2
* No history of brain metastases

--Prior/Concurrent Therapy--

* Biologic therapy: At least 4 weeks since prior biologic therapy
* Chemotherapy: See Disease Characteristics; No prior chemotherapy
* Endocrine therapy: No concurrent immunosuppressive drugs
* Radiotherapy: At least 4 weeks since prior radiotherapy
* Surgery: At least 2 weeks since prior major surgery
* Other: No other concurrent anticancer drug therapy or experimental therapy

--Patient Characteristics--

* Age: 18 and over
* Performance status: Karnofsky 80-100%
* Life expectancy: At least 24 weeks
* Hematopoietic: WBC at least 3,000/mm3; Platelet count at least 100,000/mm3; Hemoglobin at least 9 g/dL
* Hepatic: Bilirubin no greater than 2.0 mg/dL; SGOT/SGPT less than 3 times upper limit of normal (ULN); PT/PTT normal; Albumin normal; LDH no greater than 2 times ULN
* Renal: Creatinine no greater than 2.0 mg/dL
* Cardiovascular: No uncontrolled hypertension; No New York Heart Association class III or IV disease
* Other: HIV negative; Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception; No active autoimmune disease; No active infection requiring parenteral antibiotics; No uncontrolled diabetes mellitus; No other prior malignancy within the past 5 years except skin cancer or stage 0-II cervical cancer; No significant psychiatric disorders