Gene Therapy in Treating Patients With Stage III or Stage IV Melanoma

Phase II Study of Allovectin-7 as an Immunotherapeutic Agent in Patients With Stages III and IV Melanoma

RATIONALE: Injecting allovectin-7 into a person's melanoma cells may make the body build an immune response that will kill tumor cells.

PURPOSE: Phase II trial to study the effectiveness of gene therapy in treating patients who have stage III or stage IV melanoma that has not responded to previous treatment.

OBJECTIVES: I. Demonstrate an objective clinical response (partial or complete) with a median duration of at least 4 months in 15% of patients with stage III or IV melanoma treated with Allovectin-7. Allovectin-7 is a direct gene transfer immunotherapeutic agent.

II. Determine the benefits, risks, and side effects of Allovectin-7 in this patient population.

PROTOCOL OUTLINE: This is a multicenter study. Patients receive an intratumoral injection of Allovectin-7 once weekly for 6 weeks. At week 9, a complete disease status assessment is performed. Patients with stable or responding disease may receive additional courses of 6 injections.

PROJECTED ACCRUAL:

A total of 70 patients will be accrued for this study.

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed melanoma; Stage III with locoregional disease, in transit metastasis, or nodal disease OR Stage IV metastatic disease in skin, subcutaneous tissue, lymph node(s), and/or lung
• At least 1 metastasis for which surgery is not deemed to be a curative option
• Relapsed from or has not responded to frontline chemotherapy or biotherapy
• At least 1 measurable tumor at least 1 cm by 1 cm, but less than 5 cm by 5 cm
• No history of brain metastases or visceral metastases other than lung metastases

--Prior/Concurrent Therapy--

• Biologic therapy: See Disease Characteristics; At least 4 weeks since prior biologic therapy
• Chemotherapy: See Disease Characteristics; At least 4 weeks since 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 any other experimental therapy

--Patient Characteristics--

• Age: 18 and over
• Performance status: Karnofsky 80-100%
• Life expectancy: At least 6 months
• 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; PT/PTT normal LDH and albumin normal
• 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; 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 in the past 5 years except skin cancer or stage 0-II cervical cancer; No significant psychiatric disorders