RATIONALE: Vaccines made from peptides may make the body build an immune response to kill tumor cells. Colony-stimulating factors such as sargramostim increase the number of immune cells found in bone marrow or peripheral blood. Combining vaccine therapy with sargramostim may make a stronger immune response.

PURPOSE: This randomized phase II trial is studying vaccine therapy and sargramostim to see how well they work compared to vaccine therapy alone in treating patients who have undergone surgery for stage IIB, stage IIC, stage III, or stage IV melanoma.

Condition	Treatment or Intervention	Phase
stage II melanoma stage III melanoma Stage IV Melanoma iris melanoma ciliary body and choroid melanoma, medium/large size extraocular extension melanoma	Drug: MART-1 antigen  Drug: Montanide ISA-51  Drug: gp100 antigen  Drug: sargramostim  Drug: tyrosinase peptide  Procedure: adjuvant therapy  Procedure: biological response modifier therapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: non-specific immune-modulator therapy  Procedure: non-tumor cell derivative vaccine  Procedure: vaccine therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Compare immune response in patients with resected stage IIB, IIC, III, or IV melanoma treated with a vaccine comprising tyrosinase peptide, gp100 antigen, and MART-1 antigen emulsified with Montanide ISA-51 with vs without sargramostim (GM-CSF).

Secondary

• Compare time to relapse in patients treated with these regimens.
• Compare survival of patients treated with these regimens.

OUTLINE: This is a randomized, parallel, continuation study. Patients are stratified according to response to prior vaccination (response to 1 peptide vs response to 2 or more peptides). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive vaccination comprising tyrosinase peptide, gp100 antigen, and MART-1 antigen emulsified with Montanide ISA-51 subcutaneously (SC) on day 1 of weeks 0, 26, 52, 78, and 104 (total of 5 vaccinations).
• Arm II: Patients receive vaccination comprising tyrosinase peptide, gp100 antigen, and MART-1 antigen emulsified with Montanide ISA-51 as in arm I. Patients also receive sargramostim (GM-CSF) SC on days 1-5 of weeks 0, 26, 52, 78, and 104. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed at 2-4 weeks, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 40 patients (20 per treatment arm) will be accrued for this study within 1 year.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of melanoma, meeting 1 of the following stage criteria:
• Stage IIB, IIC, III, or IV cutaneous disease
• Stage III or IV mucosal or ocular disease
• Resected disease
• At high risk of relapse
• Completed protocol
• or
• AND meets all of the following criteria:
• Received all injections AND has shown evidence of an immune response
• No recurrence of melanoma
• No more than 12 months since final injection on either protocol
• No grade 3 or 4 toxicity attributed to prior vaccine regimen
• HLA-A2.1 positive
• Failed, not eligible for, or refused prior interferon alfa therapy

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,000/mm^3
• Granulocyte count ≥ 1,500/mm^3
• Hemoglobin ≥ 9.0 g/dL
• Platelet count ≥ 100,000/mm^3
• No coagulation or bleeding disorders

Hepatic

• Bilirubin ≤ 2.0 mg/dL
• SGOT and SGPT ≤ 2.5 times upper limit of normal
• Hepatitis B surface antigen negative
• Hepatitis C antibody negative

Renal

• Creatinine ≤ 2.0 mg/dL

Cardiovascular

• No major cardiovascular disease

Pulmonary

• No major respiratory disease
• No pneumonia

Immunologic

• No prior uveitis or autoimmune inflammatory eye disease
• No major systemic infections (e.g., sepsis)
• No known allergy to study drugs
• No immune hemolytic anemia
• No other active autoimmune disease
• HIV negative

Other

• No major gastrointestinal disease
• No other malignancy within the past 5 years except curatively treated squamous cell or basal cell skin cancer or carcinoma of the cervix (more than 30 days since curative treatment)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study treatment

PRIOR CONCURRENT THERAPY: Biologic therapy

• See Disease Characteristics

Chemotherapy

• Not specified

Endocrine therapy

• No concurrent systemic, ocular, or inhaled corticosteroids

Radiotherapy

• No prior radiotherapy for melanoma since completion of or

Surgery

• See Disease Characteristics

Other

• No other prior therapy for melanoma since completion of or

California
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90089,  United States; Recruiting

Study chairs or principal investigators

Jeffrey S. Weber, MD, PhD,  Study Chair,  University of Southern California   

Study ID Numbers:  CDR0000378033; LAC-USC-10M038; LAC-USC-042011; LAC-USC-0A1033; NCI-6618; NCT00089063
Record last reviewed:  July 2004
Last Updated:  February 15, 2005
Record first received:  August 4, 2004
ClinicalTrials.gov Identifier:  NCT00089063
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08