vaccine therapy in treating patients who have stage ii, stage iii, or stage iv melanoma

Conditions: Melanoma (Skin)

Summary: rationale: vaccines may make the body build an immune response to kill tumor cells. purpose: phase i/ii trial to study the effectiveness of vaccine therapy in treating patients who have stage ii, stage iii, or stage iv melanoma.

objectives: i. determine the safety and the maximum tolerated dose of vaccines containing two adenoviral vectors encoding the melanoma antigens melan-a/mart-1 and gp100 in patients with stage ii-iv melanoma. ii. assess the dose-response changes in the frequency of mart-1 and gp100 reactive t cells (cd4+ and cd8+) in patients receiving one of three different vaccine regimens. iii. assess the t-cell response to one melanoma antigen following three treatments with the other antigen in these patients. iv. assess the effect of concomitant vaccination with both antigens on t-cell response in these patients. outline: this is a dose escalation study. patients are sequentially enrolled on 1 of 3 treatment arms. each treatment arm has 3 groups. arm i: patients receive ad2/mart-1v2 vaccine and ad2/gp100v2 vaccine intradermally (id) at the lowest dose level once every three weeks for either 6 or 15 weeks depending on assignment. arm ii: patients receive ad2/gp100v2 vaccine and ad2/mart-1v2 vaccine id at the mid-range dose level once every three weeks for either 6 or 15 weeks depending on assignment. arm iii: patients receive ad2/mart-1v2 vaccine and ad2/gp100v2 vaccine id at the highest dose level once every three weeks for either 6 or 15 weeks depending on assignment. cohorts of 3-6 patients receive escalating doses of ad2/mart-1v2 and/or ad2/gp100v2 vaccines in each arm until the maximum tolerated dose (mtd) is reached. the mtd is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. patients are followed at 3 months, 6 months, and 1 year after completion of treatment. projected accrual: a total of 24-36 patients will be accrued over 1 year.

Eligibility criteria:
disease characteristics: histologically confirmed stage ii, iii, or iv cutaneous malignant melanoma no evidence of disease at time of entry to protocol definitive complete surgical resection within past 12 months hla-a2 positive patient characteristics: age: 18 or over performance status: ecog 0-1 life expectancy: not specified hematopoietic: wbc at least 3,000 cells/mm3 platelet count at least 100,000 cells/mm3 no clinically significant hematologic disease that would preclude study hepatic: sgot and sgpt less than 2 times upper limit of normal bilirubin less than 2 mg/dl no clinically significant hepatic disease that would preclude study renal: creatinine less than 2 mg/dl no clinically significant renal disease that would preclude study cardiovascular: no clinically significant cardiac disease that would preclude study other: no clinically significant underlying condition that would preclude study no significant autoimmune disease or other major immune system disorder hiv negative htlv negative hepatitis b and c negative no active infection requiring parenteral antibiotics no psychiatric disorder that could hinder protocol compliance not pregnant or nursing fertile patients must use effective contraception prior concurrent therapy: biologic therapy: no prior or concurrent immunotherapy at least 3 months since prior interferon therapy chemotherapy: no prior or concurrent chemotherapy endocrine therapy: no prior or concurrent immunosuppressants radiotherapy: at least 4 weeks since prior radiotherapy surgery: at least 4 weeks since prior surgery other: no other prior or concurrent experimental anticancer therapy

Keywords: stage ii melanoma stage iii melanoma stage iv melanoma