Vaccine Therapy in Treating Patients With Primary Stage II Melanoma

Adjuvant Ganglioside GM2-KLH/QS-21 Vaccination: Post-Operative Adjuvant Ganglioside GM2-KLH/QS-21 (BMS-248479) Vaccination Treatment After Resection of Primary Cutaneous Melanoma Thicker Than 1.5mm (AJCC/UICC Stage II, T3-T4N0M0), a 2-Arm Multicenter Randomized Phase III Trial vs. Observation

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. It is not yet known whether vaccine therapy is more effective than observation alone for melanoma.

PURPOSE: This randomized phase III trial is studying vaccine therapy to see how well it works compared to observation alone in treating patients with primary stage II melanoma.

OBJECTIVES:

• Compare the effect of immunization with GM2-KLH and QS21 to observation on the disease-free survival of patients with primary cutaneous stage II melanoma after adequate surgery.
• Determine overall survival and toxicity in the two treatment arms.

OUTLINE: This is a randomized, open-label, parallel, multicenter study. Patients are stratified according to participating center, tumor thickness (greater than 1.5 to 3.0 mm vs greater than 3.0 to 4.0 mm vs greater than 4.0 mm), gender, ulceration (yes vs no), and presence of additional staging procedures of regional lymph nodes (yes vs no). Patients are randomized to one of two arms.

• Arm I: Patients are vaccinated with GM2-KLH and QS21 subcutaneously on day 1 of weeks 1-4, 12, 24, 36, 48, 60, 72, 84, 96, 120, and 144 for a total of 14 vaccinations.
• Arm II: Patients undergo observation. Patients are followed every 6 months for 7 years.

PROJECTED ACCRUAL: A total of 1300 patients (650 per arm) will be accrued for this study within 36 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed primary stage II melanoma greater than 1.5 mm without evidence of lymph node metastases

  • T3 or T4, N0, M0
  • Must originate in the skin

• Wide excision with a minimum of 1-2 cm margin surrounding primary lesion or biopsy scar

  • No more than 56 days since definitive surgical treatment (wide excision)
  • No more than 12 weeks since primary surgery

• No clinical, radiological, or pathological evidence of incompletely resected disease, lymph node metastases, in-transit metastasis, or any distant metastatic disease

PATIENT CHARACTERISTICS:

Age:

• 18 to 80

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9.8 g/dL

Hepatic:

• SGOT/SGPT no greater than 2 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2 times ULN
• LDH no greater than 2 times ULN
• Bilirubin no greater than 2 times ULN
• Hepatitis B and C negative

Renal:

• Creatinine normal

Other:

• Not pregnant or nursing
• Negative pregnancy test
• No prior or other concurrent cancer except carcinoma in situ of the cervix or basal or squamous cell skin cancer
• No autoimmune disorders
• No conditions requiring systemic treatment with immunosuppressive drugs including treatment with systemic corticosteroids
• No history of CNS demyelinating or inflammatory disease
• No hereditary or acquired peripheral neuropathy
• No other significant medical or surgical condition or psychiatric disorders requiring medication that would preclude study
• No history of severe allergic reaction to shellfish
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior immunotherapy
• No other concurrent biologic therapy

Chemotherapy:

• No prior systemic chemotherapy
• No concurrent cytotoxic chemotherapy

Endocrine therapy:

• No concurrent hormonal therapy except replacement therapy
• No concurrent corticosteroids
• No concurrent chronic systemic steroids

Radiotherapy:

• No prior adjuvant radiotherapy
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics

Other:

• No prior preoperative infusion or perfusion therapy
• No concurrent immunosuppressive medications
• No other concurrent anticancer therapy