A Randomized Phase II Trial to Determine the Immune Response to a Mutated gp100 Melanoma Peptide (209-2M) Vaccine in HLA-A2 Positive Patients With a >1mm Melanoma on Initial Biopsy

PRIMARY OBJECTIVES: I. To define the toxicity of administration of gp100: 209-217 (210M) (gp100:209-217[210M] peptide vaccine) and the human papillomavirus (HPV) 16 E7(12-20) peptide (HPV16E7:12-20 peptide vaccine), with adjuvant Montanide ISA-51 (incomplete Freund's adjuvant), to patients who present with a primary melanoma > 1 mm thick. II. To measure the T-cell response to the modified self-gp100: 209-217 (210M) peptide and the unmodified parental glycoprotein 100 (gp100) peptide. III. To measure the T-cell response to the control human leukocyte antigen (HLA)-A2.1 restricted cytotoxic T-lymphocyte (CTL) epitope of papilloma virus HPV16E7:12-20. IV. To determine whether analysis of antigen-specific T-cells using specific HLA-A2/peptide tetramers is an effective method for monitoring the immune response of patients undergoing peptide vaccination and to compare it to enzyme-linked immunosorbent spot (ELISPOT), limiting dilution analysis (LDA) and measurement of intracellular cytokine production (fastimmune). V. To determine whether there is a difference between the induction of primary peptide-specific T-cell immune responses to the self gp100 peptide versus the foreign E7 peptide. VI. To compare the immune response induced by vaccinating every 2 weeks for 6 months (a total of 13 vaccinations) vs. every 3 weeks for 6 months (a total of 9 vaccinations). OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive gp100:209-217(210M) peptide vaccine and HPV16E7:12-20 peptide vaccine mixed with incomplete Freund's adjuvant subcutaneously (SC) every 2 weeks for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive gp100:209-217(210M) peptide vaccine and HPV16E7:12-20 peptide vaccine mixed with incomplete Freund's adjuvant SC every 3 weeks for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity. In both arms, patients undergo sentinel lymph node biopsy approximately 10 days after the second vaccination. Patients with positive lymph nodes undergo complete lymph node dissection and resume vaccinations. After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then yearly thereafter.