RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Biological therapies such as sargramostim and interferon alfa use different ways to stimulate the immune system and stop cancer cells from growing. It is not yet known if vaccine therapy if more effective with or without biological therapy for melanoma.

PURPOSE: Randomized phase II trial to compare the effectiveness of vaccine therapy with or without biological therapy in treating patients who have metastatic melanoma.

Condition	Treatment or Intervention	Phase
Stage IV Melanoma Recurrent Melanoma	Drug: MART-1 antigen  Drug: Montanide ISA-51  Drug: gp100 antigen  Drug: interferon alfa  Drug: sargramostim  Drug: tyrosinase peptide  Procedure: biological response modifier therapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: interferon therapy  Procedure: non-specific immune-modulator therapy  Procedure: non-tumor cell derivative vaccine  Procedure: vaccine therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine immune response of vaccination with melanoma associated antigens (MART-1:27-35, gp100:209-217 (210M), and tyrosinase:368-376 (370D)) on the number of peptide specific CD8+ T-cell precursors in HLA-A2 positive patients with metastatic melanoma.
• Determine the influence of sargramostim (GM-CSF) and/or interferon alfa-2b (IFN-A) on the immune responses of these patients and toxicity of this melanoma peptide vaccine.
• Determine any antitumor and anti-pigmentary response that may result from immunization against MART-1, gp100 and tyrosinase peptides, and determine the relationship between such clinical observations and immune responses against lineage antigens with or without GM-CSF and/or IFN-A.
• Compare the relapse free survival and overall survival of patients treated with melanoma peptide vaccine alone or in combination with GM-CSF and/or IFN-A.

OUTLINE: This is a randomized, multicenter study.

Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients receive multiepitope peptide (MEP) vaccine comprising MART-1:27-35, gp100:209-217 (210M), and tyrosinase:368-376 (370D) peptides. Each peptide is separately emulsified in Montanide ISA-51 and administered subcutaneously (SC) (for a total of 2 injections per peptide) on days 1 and 15.
• Arm II: Patients receive MEP vaccine as in arm I and sargramostim (GM-CSF) subcutaneously (SC) daily on days 1-14.
• Arm III: Patients receive MEP vaccine as in arm I and interferon alfa-2b SC three times a week.
• Arm IV: Patients receive MEP vaccine as in arm I, GM-CSF as in arm II, and interferon alfa-2b as in arm III. Treatment continues every 4 weeks for a maximum of 13 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 92 patients (23 per arm) will be accrued for this study within 13-16 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically proven stage IV melanoma
• Measurable disease
• At least 1 lesion must be a minimum of 1.0 cm in diameter
• Bone metastases are not considered to be measurable disease
• No prior radiotherapy to area of measurable disease unless there is clearly progressive disease in this site or measurable disease exists outside the area of prior radiotherapy
• HLA-A2 positive
• No brain disease by MRI or CT scan within 4 weeks prior to randomization
• Prior brain disease allowed if no evidence of active disease by 2 successive MRI evaluations completed at least 3 months apart

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 4,000/mm^3
• Platelet count at least 100,000/mm^3
• Lymphocyte count greater than 700/mm ^3

Hepatic:

• SGOT no greater than 2 times upper limit of normal (ULN)
• Bilirubin no greater than 2 times ULN
• Alkaline phosphatase and lactic dehydrogenase no greater than 2 times ULN

Renal:

• Creatinine no greater than 1.8 mg/dL

Other:

• No significant detectable infection
• HIV negative
• No other malignancy within the past 5 years except:
• Any carcinoma in situ
• Lobular carcinoma in situ of the breast
• Carcinoma in situ of the cervix
• Atypical melanocytic hyperplasia
• Melanoma in situ
• Basal cell or squamous cell skin cancer
• No autoimmune disorders or conditions of immunosuppression
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No prior MART-1:27-35, gp100:209-217 (210M), or tyrosinase:368-376 (370D) peptide
• Greater than 4 weeks since prior adjuvant immunotherapy, including sargramostim (GM-CSF) or interferon alfa-2b

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy:

• At least 2 weeks since prior and no concurrent systemic corticosteroids, including oral steroids (i.e., prednisone, dexamethasone); continuous use of topical steroid creams or ointments; or any inhalers containing steroids

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy for local control or palliation and recovered

Surgery:

• Recovered from any prior major surgery

Arizona
      CCOP - Scottsdale Oncology Program, Scottsdale,  Arizona,  85259-5404,  United States
Georgia
      Emory University Hospital - Atlanta, Atlanta,  Georgia,  30322,  United States
      Veterans Affairs Medical Center - Atlanta (Decatur), Decatur,  Georgia,  30033,  United States
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States
      CCOP - Evanston, Evanston,  Illinois,  60201,  United States
      Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago,  Illinois,  60611,  United States
      Veterans Affairs Medical Center - Lakeside Chicago, Chicago,  Illinois,  60611-4494,  United States
Indiana
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5289,  United States
      Veterans Affairs Medical Center - Indianapolis (Roudebush), Indianapolis,  Indiana,  46202,  United States
Iowa
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States
Louisiana
      CCOP - Ochsner, New Orleans,  Louisiana,  70121,  United States
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231,  United States
Massachusetts
      Beth Israel Deaconess Medical Center, Boston,  Massachusetts,  02215,  United States
      Tuft-New England Medical Center, Boston,  Massachusetts,  02111,  United States
Michigan
      CCOP - Kalamazoo, Kalamazoo,  Michigan,  49007-3731,  United States
New Jersey
      Cancer Institute of New Jersey, New Brunswick,  New Jersey,  08903,  United States
      CCOP - Northern New Jersey, Hackensack,  New Jersey,  07601,  United States
New York
      Albert Einstein Clinical Cancer Center, Bronx,  New York,  10461,  United States
Ohio
      CCOP - Toledo Community Hospital, Toledo,  Ohio,  43623-3456,  United States
      Ireland Cancer Center, Cleveland,  Ohio,  44106-5065,  United States
Pennsylvania
      CCOP - Geisinger Clinic and Medical Center, Danville,  Pennsylvania,  17822-2001,  United States
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111,  United States
      University of Pennsylvania Cancer Center, Philadelphia,  Pennsylvania,  19104,  United States
      University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15213-3489,  United States
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57104,  United States
Texas
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States
Virginia
      Cancer Center at the University of Virginia, Charlottesville,  Virginia,  22908,  United States
Wisconsin
      CCOP - Marshfield Medical Research and Education Foundation, Marshfield,  Wisconsin,  54449,  United States
      CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay,  Wisconsin,  54301,  United States
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-0001,  United States
      Veterans Affairs Medical Center - Madison, Madison,  Wisconsin,  53705-2286,  United States

Study chairs or principal investigators

John Munn Kirkwood, MD,  Study Chair,  University of Pittsburgh Cancer Institute   

Study ID Numbers:  CDR0000068263; E-1696
Record last reviewed:  June 2003
Last Updated:  October 13, 2004
Record first received:  October 4, 2000
ClinicalTrials.gov Identifier:  NCT00006385
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08