Vaccine Therapy and/or Sargramostim in Treating Patients With Locally Advanced or Metastatic Melanoma
Recruitment status was Active, not recruiting
RATIONALE: Vaccines 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. It is not yet known which treatment regimen is more effective for melanoma.
PURPOSE: This randomized phase III trial is studying peptide vaccine therapy and/or sargramostim and comparing how well they work in treating patients with locally advanced or metastatic melanoma.
Biological: MART-1 antigen
Biological: gp100 antigen
Biological: incomplete Freund's adjuvant
Biological: tyrosinase peptide
Procedure: adjuvant therapy
|Study Design:||Allocation: Randomized
Primary Purpose: Treatment
|Official Title:||A Randomized, Placebo-Controlled Phase III Trial of Yeast Derived GM-CSF Versus Peptide Vaccination Versus GM-CSF Plus Peptide Vaccination Versus Placebo in Patients With "No Evidence of Disease" After Complete Surgical Resection of "Locally Advanced" and/or Stage IV Melanoma|
- Overall survival at 2 years [ Designated as safety issue: No ]
- Two-year survival [ Designated as safety issue: No ]
- Time to progression [ Designated as safety issue: No ]
|Study Start Date:||December 1999|
- Compare overall survival and disease-free survival in HLA-A2-positive or negative patients with completely resected locally advanced or metastatic melanoma treated with or without sargramostim (GM-CSF).
- Compare overall survival and disease-free survival in HLA-A2-positive patients treated with peptide vaccination comprised of tyrosinase:368-376, gp100:209-217 (210M) antigen, and MART-1:27-35 peptide vs no peptide vaccination.
- Compare the influence of GM-CSF on circulating dendritic cell numbers and subpopulations in peripheral blood of patients treated with or without GM-CSF.
- Determine whether immunization with peptides with or without GM-CSF elicits a measurable T-cell response in HLA-A2-positive patients.
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified by HLA-A2 status (positive vs negative), site of metastases this occurrence (visceral vs nonvisceral vs visceral and nonvisceral vs no metastases), and number of metastases this occurrence (1 vs 2 or 3 vs 4 or more vs 0).
Patients are assigned to one of two treatment groups based on HLA-A2 status.
Group A (HLA-A2 positive): Patients are randomized to 1 of 4 treatment arms.
- Arm I: Patients receive sargramostim (GM-CSF) subcutaneously (SC) daily on days 1-14. Patients receive peptide vaccination comprising the following 3 peptides: tyrosinase:368-376, gp100:209-217 (210M) antigen (gp100), and MART-1:27-35 peptide. Each peptide is emulsified separately in Montanide ISA-51 (ISA-51) and administered separately via 2 SC injections into 3 different sites on days 1 and 15 of course 1 and on day 1 of subsequent courses.
- Arm II: Patients receive GM-CSF placebo SC on days 1-14. Patients receive peptide vaccination as in arm I.
- Arm III: Patients receive GM-CSF as in arm I. Patients receive peptide vaccination placebo comprising tyrosinase placebo, gp100 placebo, and MART -1 placebo. Each peptide placebo is emulsified separately in ISA-51 and administered separately via 2 SC injections into 3 different sites on days 1 and 15 of course 1 and on day 1 of subsequent courses.
- Arm IV: Patients receive GM-CSF placebo as in arm II and peptide vaccination placebo as in arm III.
Group B (HLA-A2 negative): Patients are randomized to 1 of 2 treatment arms.
- Arm V: Patients receive GM-CSF SC as in arm I.
- Arm VI: Patients receive GM-CSF placebo as in arm II. Treatment in both groups repeats every 4 weeks for 13 courses in the absence of disease progression. Patients who develop unresectable recurrent disease are taken off study, whereas those who develop resectable recurrent disease undergo complete resection and may continue treatment on the arm to which they were originally randomized for 6 additional courses or until they complete 1 year of protocol treatment. Patients who develop a second recurrence are taken off study.
Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for up to 10 years.
PROJECTED ACCRUAL: A total of 800 patients will be accrued for this study within 4.4 years.
|Study Chair:||David H. Lawson, MD||Winship Cancer Institute of Emory University|
|Study Chair:||Kim A. Margolin, MD||Beckman Research Institute|