Vaccine Therapy With or Without Biological Therapy in Treating Patients With Metastatic Melanoma

Melanoma (Skin) Clinical Trial

Official title:

Phase II Evaluation of Immunization With an HLA-A2 Multi-Epitope Peptide Vaccine Containing MART-1 (NSC #672643), gp100 (NSC #683472), and Tyrosinase (NSC #699048) Peptides Alone or in Combination With GM-CSF, IFN Alpha-2b, or GM-CSF + IFN Alpha-2b in Patients With Metastatic Melanoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006385
• Other study ID #: CDR0000068263
• Secondary ID: E-1696
• Status: Completed
• Phase: Phase 2
• First received: October 4, 2000
• Last updated: November 5, 2011
• Start date: September 2000

Study information

• Verified date: December 2002
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. primary completion date: October 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

Intervention

Biological:
• MART-1 antigen

• gp100 antigen

• incomplete Freund's adjuvant

• recombinant interferon alfa

• sargramostim

• tyrosinase peptide

Locations

Country	Name	City	State
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Tuft-New England Medical Center	Boston	Massachusetts
United States	Albert Einstein Clinical Cancer Center	Bronx	New York
United States	Cancer Center at the University of Virginia	Charlottesville	Virginia
United States	Robert H. Lurie Comprehensive Cancer Center, Northwestern University	Chicago	Illinois
United States	Veterans Affairs Medical Center - Lakeside Chicago	Chicago	Illinois
United States	Ireland Cancer Center	Cleveland	Ohio
United States	CCOP - Geisinger Clinic and Medical Center	Danville	Pennsylvania
United States	Veterans Affairs Medical Center - Atlanta (Decatur)	Decatur	Georgia
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	CCOP - Evanston	Evanston	Illinois
United States	CCOP - St. Vincent Hospital Cancer Center, Green Bay	Green Bay	Wisconsin
United States	CCOP - Northern New Jersey	Hackensack	New Jersey
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Veterans Affairs Medical Center - Indianapolis (Roudebush)	Indianapolis	Indiana
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	Veterans Affairs Medical Center - Madison	Madison	Wisconsin
United States	CCOP - Marshfield Medical Research and Education Foundation	Marshfield	Wisconsin
United States	Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	CCOP - Scottsdale Oncology Program	Scottsdale	Arizona
United States	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	CCOP - Wichita	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (4)

Kirkwood JM, Lee S, Land S, et al.: E1696: final analysis of the clinical and immunological results of a multicenter ECOG phase II trial of multi-epitope peptide vaccination for stage IV melanoma with MART-1 (27-35), gp100 (209-217, 210M), and tyrosinase

Kirkwood JM, Lee S, Land S, et al.: E1696: phase II trial of multi-epitope peptide vaccination for melanoma with MGT (MART-1 (27-35), gp100 (209-217, 210M) and tyrosinase (368-376, 370D))+/- IFN alfa-2b and GM-CSF--immunological and clinical results. [Abs

Kirkwood JM, Lee S, Moschos SJ, Albertini MR, Michalak JC, Sander C, Whiteside T, Butterfield LH, Weiner L. Immunogenicity and antitumor effects of vaccination with peptide vaccine+/-granulocyte-monocyte colony-stimulating factor and/or IFN-alpha2b in adv — View Citation

Schaefer C, Butterfield LH, Lee S, Kim GG, Visus C, Albers A, Kirkwood JM, Whiteside TL. Function but not phenotype of melanoma peptide-specific CD8(+) T cells correlate with survival in a multiepitope peptide vaccine trial (ECOG 1696). Int J Cancer. 2012 — View Citation