Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	18 and over	NCI, Other	CDR0000067568 ECOG-4697, SWOG-E4697, NCT00005034

Trial Description

Summary

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.

Further Study Information

OBJECTIVES:

• 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.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically proven completely resected melanoma including one of the following:

• Any locoregional recurrence after prior adjuvant interferon or failure on SWOG-0008

• Any local recurrence after adequate surgical excision of the original primary

• Mucosal melanoma

• Stage IV disease including:

• Cutaneous melanoma

• Ocular melanoma

• Mucosal melanoma

• Multiple primary lesions allowed

• If ineligible for SWOG-0008 or are determined by managing physician to be medically unfit to receive standard high-dose interferon, patients with one of the following may be eligible:

• Any clinically evident satellite or intransit disease

• Stage III disease with gross extracapsular extension

• Recurrence in previously resected nodal basin

• Four or more involved lymph nodes or matted lymph nodes

• Ulcerated primary melanoma and any involved lymph nodes

• Known HLA-A2 status

• Rendered free of disease with negative margins by surgical means only

• Ineligible if rendered free of disease by nonsurgical means

• Must be randomized within 16 weeks of surgical resection

• If more than one surgical procedure is required to render the patient disease free, all required surgeries must be completed within this 16-week time period

• Patients with bone pain must have a negative bone scan

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0 or 1

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm^3

• Platelet count at least 100,000/mm^3

Hepatic:

• SGOT no greater than 2 times upper limit of normal (ULN)

• Bilirubin no greater than 2 times ULN

• LDH normal

• Alkaline phosphatase no greater than ULN (1.25 times ULN if negative CT scan or MRI of liver and negative bone scan or negative PET scan)

Renal:

• Creatinine no greater than 1.8 mg/dL

Other:

• No active infection requiring treatment with IV antibiotics

• No other significant medical, surgical, or psychiatric condition or requirement for medication or treatment that would preclude study compliance

• No diagnosis or evidence of organic brain syndrome or significant impairment of basal cognitive function that would preclude study compliance

• Able to self administer or arrange for administration of subcutaneous injections

• No other malignancy within the past 5 years except any of the following curatively treated cancers:

• Lobular carcinoma in situ of the breast

• Carcinoma in situ of the cervix

• Any other in situ cancer

• Atypical melanocytic hyperplasia

• Clark's level I melanoma (melanoma in situ)

• Basal cell or squamous cell skin cancer

• No autoimmune disorder

• No condition of immunosuppression

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 18 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics

• No prior sargramostim (GM-CSF)

• No prior MART-1:27-35 peptide, tyrosinase:368-376, or gp100:209-217 (210M) antigen

• No prior adjuvant biologic therapy after resection(s) that rendered the patient disease-free with negative margins

• One prior systemic regimen after prior surgery allowed if completed at least 8 weeks ago

• Chemotherapy and biologic therapy administered together as one planned treatment count as one regimen

Chemotherapy:

• See Biologic therapy

• No prior adjuvant chemotherapy after resection(s) that rendered the patient disease-free with negative margins

Endocrine therapy:

• At least 2 weeks since prior systemic corticosteroids, including oral steroids (e.g., prednisone or dexamethasone)

• At least 2 weeks since prior continuous use of topical steroid creams or ointments or any steroid-containing inhalers

• Concurrent replacement doses of steroids for adrenal insufficiency allowed

• No concurrent systemic corticosteroids, including oral steroids (e.g., prednisone or dexamethasone)

• No concurrent continuous use of topical steroid creams or ointments or any steroid-containing inhalers

Radiotherapy:

• At least 30 days since prior radiotherapy, including after the resection

Surgery:

• See Disease Characteristics

• See Biologic therapy

• See Chemotherapy

• See Radiotherapy

Other:

• No prior adjuvant limb perfusion after resection(s) that rendered the patient disease-free with negative margins

• No concurrent IV antibiotics

Trial Contact Information

Trial Lead Organizations/Sponsors

Eastern Cooperative Oncology Group

David H. Lawson

Study Chair

Kim Allyson Margolin

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00005034
Information obtained from ClinicalTrials.gov on March 18, 2010

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