Vaccine Therapy in Treating Patients With Stage IIIB, Stage IIIC, or Stage IV Melanoma

Study Overview
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Brief Summary
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RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. PURPOSE: This randomized phase I/II trial is studying three different doses of a vaccine and comparing them to see how well they work in treating patients with stage IIIB, stage IIIC, or stage IV melanoma.

Detailed Description
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OBJECTIVES: Determine the immune response in patients with stage IIIB, IIIC, or IV melanoma treated with vaccine comprising multiple synthetic melanoma peptides, Montanide ISA-51, and sargramostim (GM-CSF). OUTLINE: This is a randomized study. Patients are randomized to 1 of 3 treatment arms. Arm I: Patients receive vaccine comprising low-dose multiple synthetic melanoma peptides, Montanide ISA-51, and sargramostim (GM-CSF) on days 1, 8, 15, 29, 36, and 43. Arm II: Patients receive vaccine comprising medium-dose multiple synthetic melanoma peptides, Montanide ISA-51, and GM-CSF as in arm I. Arm III: Patients receive vaccine comprising high-dose multiple synthetic melanoma peptides, Montanide ISA-51, and GM-CSF as in arm I. On day 22, the lymph node draining the vaccination site is removed to determine whether the immune system is responding to the vaccine. PROJECTED ACCRUAL: A maximum of 38 patients will be accrued for this study.

Official Title
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Vaccination With Multiple Synthetic Melanoma Peptides Recognized by Helper T-Cells in Patients With Advanced Melanoma

Conditions
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Intraocular Melanoma, Melanoma (Skin)

Intervention / Treatment
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* Biological: IFA
* Biological: 6MHP
* Biological: GM-CSF


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of stage IIIB, IIIC, or IV melanoma HLA-DR1, -DR4, -DR11, -DR13, or -DR15 positive Brain metastases allowed at the discretion of the principle investigator PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic Absolute neutrophil count > 1,000/mm^3 Platelet count > 100,000/mm ^3 Hemoglobin > 9 g/dL Hepatic Liver function tests ≤ 2.5 times upper limit of normal (ULN) Renal Creatinine ≤ 1.5 times ULN Cardiovascular No New York Heart Association class III or IV heart disease Other Prior diagnosis of other cancer allowed Not pregnant or nursing Weight ≥ 110 pounds No uncontrolled diabetes PRIOR CONCURRENT THERAPY: Biologic therapy More than 4 weeks since prior growth factors More than 4 weeks since prior allergy shots More than 12 weeks since prior melanoma vaccine therapy* NOTE: *Prior melanoma vaccine allowed only for patients with disease progression during or after administration of the vaccine No prior vaccination with any of the peptides used in this study Chemotherapy More than 4 weeks since prior chemotherapy Endocrine therapy More than 4 weeks since prior steroids Radiotherapy More than 4 weeks since prior radiotherapy Surgery Not specified Other More than 1 month since prior investigational drugs or therapies No other concurrent investigational drugs or therapies

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A. 6MHP vaccine 200 mcg<br>vaccine containing 6 melanoma helper peptides, at 200 mcg per peptide, with GM-CSF and IFA (Montanide ISA-51) | Biological: IFA<br>* vaccine adjuvant<br>* Other names: incomplete Freund's adjuvant, Montanide ISA-51;Biological: 6MHP<br>* melanoma helper peptides<br>* Other names: multi-epitope melanoma peptide vaccine;Biological: GM-CSF<br>* vaccine adjuvant<br>* Other names: sargramostim;|
| Experimental: Arm B. 6MHP vaccine 400 mcg<br>vaccine containing 6 melanoma helper peptides, at 400 mcg per peptide, with GM-CSF and IFA (Montanide ISA-51) | Biological: IFA<br>* vaccine adjuvant<br>* Other names: incomplete Freund's adjuvant, Montanide ISA-51;Biological: 6MHP<br>* melanoma helper peptides<br>* Other names: multi-epitope melanoma peptide vaccine;Biological: GM-CSF<br>* vaccine adjuvant<br>* Other names: sargramostim;|
| Experimental: Arm C. 6MHP vaccine 800 mcg<br>vaccine containing 6 melanoma helper peptides, at 800 mcg per peptide, with GM-CSF and IFA (Montanide ISA-51) | Biological: IFA<br>* vaccine adjuvant<br>* Other names: incomplete Freund's adjuvant, Montanide ISA-51;Biological: 6MHP<br>* melanoma helper peptides<br>* Other names: multi-epitope melanoma peptide vaccine;Biological: GM-CSF<br>* vaccine adjuvant<br>* Other names: sargramostim;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Dose-limiting toxicity | Toxicities measured by CTCAE. | During study period | 
| Immunogenicity | Melanoma peptide-specific helper T cell responses in the sentinel immunized node (SIN) on day 22. | day 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune response in the blood | Immune response measured in the blood, by proliferation assay, over time during the study. | day 50 | 
| DTH response | Delayed-type hypersensitivity response to tumor peptides | by day 85 | 
| Clinical outcome | Clinical tumor response | during the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III melanoma, stage IV melanoma, recurrent melanoma, ciliary body and choroid melanoma, medium/large size, extraocular extension melanoma, iris melanoma, recurrent intraocular melanoma