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
- 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.
Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Treatment
Overall survival at 2 years
David H. Lawson, MD
Winship Cancer Institute of Emory University
United States: Federal Government