Patient case: 47-year-old male with melanoma; genetic feature: APC loss of function

Clinical trial: Vaccine Therapy in Treating Patients With Melanoma

Summary: RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Vaccine therapy may be an effective treatment for melanoma.
  PURPOSE: Randomized phase II trial to study the effectiveness of three vaccine therapy regimens in treating patients who have melanoma.

Detailed description: OBJECTIVES:
  -  Compare the immunologic activity of three different schedules of peptide immunization with gp100:209-217 (210M) or gp100:17-25 antigen and tyrosinase:368-376 (370D), tyrosinase:240-251 (244S), tyrosinase:206-214 (closed to accrual 11/05/01), or tyrosinase-related protein-1 (ORF3):1-9 peptide (closed to accrual 11/05/01) emulsified in Montanide ISA-51 in patients with melanoma at high risk for recurrence.
  -  Compare the response rate to treatment with interleukin-2 (IL-2) after being immunized with this regimen with the usual response rate to IL-2 in this patient population.
  -  Determine whether an exploratory cohort of HLA-A2-positive patients demonstrate immunologic activity to immunization with 2 peptides emulsified together.
  OUTLINE: This is a randomized study. Patients are stratified according to HLA type (A0201 vs A1 vs A3 vs A24 vs A31). (HLA-A24 and HLA-A31 closed to accrual 11/05/01). Patients are randomized to 1 of 3 treatment arms and are given an assigned vaccine, which is emulsified in Montanide ISA-51.
  -  HLA typing:
  -  HLA-A2: gp100:209-217 (210M) and tyrosinase:368-376 (370D)
  -  HLA-A1: tyrosinase:240-251 (244S)
  -  HLA-A3: gp100:17-25
  -  HLA-A24: tyrosinase:206-214 (closed to accrual 11/05/01)
  -  HLA-A31: tyrosinase-related protein-1 (ORF3):1-9 (closed to accrual 11/05/01)
  -  Arm I: Patients receive assigned vaccine subcutaneously (SC) weekly for 10 weeks followed by 3 weeks of no treatment.
  -  Arm II: Patients receive assigned vaccine SC on days 1, 22, 43, and 64.
  -  Arm III: Patients receive assigned vaccine SC on days 1-4, 22-25, 43-46, and 64-67.
  Treatment in all arms repeats every 13 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
  After the completion of the randomized arms of HLA-A2 patients, additional HLA-A2 patients receive immunization with gp100:209-217 (210M) and tyrosinase:368-376 (370D) emulsified in Montanide ISA-51 SC once every 3 weeks for 4 courses.
  Patients with progressive disease may receive interleukin-2 IV over 15 minutes every 8 hours for up to 4 days. Treatment repeats every 10-14 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease or mixed or partial response to treatment may receive additional courses every 2 months.
  Patients are followed at 6 months.
  PROJECTED ACCRUAL: A total of 324 patients (19-33 per arm for the HLA-A0201 stratum, 13-16 per arm for the other 4 strata, and 33 per the additional HLA-A2 cohort) will be accrued for this study within 2 years. (HLA-A24 and HLA-A31 closed to accrual 11/05/01).

Eligibility: DISEASE CHARACTERISTICS:
  -  Diagnosis of melanoma, including one of the following characteristics:
  -  Lesions at least 1.5 mm in thickness
  -  At least 1 positive lymph node
  -  Ulcerated lesion
  -  Local recurrence
  -  Metastatic lesions completely resected within the past 6 months
  -  Clinically disease free within the past 6 weeks
  -  HLA-A1, A3, A24, A31, or 0201 positive (HLA-A24 and HLA-A31 closed to accrual 11/05/01)
  -  No ocular or mucosal melanoma
  PATIENT CHARACTERISTICS:
  Age:
  -  16 and over
  Performance status:
  -  ECOG 0-1
  Life expectancy:
  -  Not specified
  Hematopoietic:
  -  WBC at least 3,000/mm^3
  -  Platelet count at least 90,000/mm^3
  Hepatic:
  -  Bilirubin no greater than 1.6 mg/dL (3.0 mg/dL in Gilbert's syndrome)
  -  AST and ALT less than 3 times normal
  -  Hepatitis B surface antigen negative
  Renal:
  -  Creatinine no greater than 2.0 mg/dL
  Cardiovascular:
  -  For interleukin-2 (IL-2) therapy:
  -  No cardiac ischemia, myocardial infarction, or cardiac arrhythmias
  -  Stress cardiac test required if abnormal EKG, symptoms of cardiac ischemia or arrhythmia, or older than 50 years
  Pulmonary:
  -  For IL-2 therapy:
  -  No obstructive or restrictive pulmonary disease
  -  FEV_1 greater than 60% predicted if prolonged history of cigarette smoking or symptoms of respiratory dysfunction
  Other:
  -  Not pregnant
  -  Negative pregnancy test
  -  Fertile patients must use effective contraception
  -  HIV negative
  -  No active systemic infections, autoimmune disease, or active primary or secondary immunodeficiency
  PRIOR CONCURRENT THERAPY:
  Biologic therapy:
  -  At least 3 weeks since prior systemic biologic therapy for melanoma
  -  No prior gp100 antigen or tyrosinase or TRP-1 peptide
  -  No other concurrent systemic biologic therapy for melanoma
  Chemotherapy:
  -  At least 3 weeks since prior systemic chemotherapy and recovered
  -  No concurrent systemic chemotherapy for melanoma
  Endocrine therapy:
  -  At least 3 weeks since prior systemic endocrine therapy for melanoma
  -  No concurrent systemic steroid therapy
  Radiotherapy:
  -  At least 3 weeks since prior systemic radiotherapy and recovered
  -  No concurrent systemic radiotherapy for melanoma
  Surgery:
  -  See Disease Characteristics

Relevance to patient case: not relevant