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

NCT ID: NCT00006385

Last Updated: 2011-11-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2000-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Melanoma (Skin)

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Interventions

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MART-1 antigen

Intervention Type BIOLOGICAL

gp100 antigen

Intervention Type BIOLOGICAL

incomplete Freund's adjuvant

Intervention Type BIOLOGICAL

recombinant interferon alfa

Intervention Type BIOLOGICAL

sargramostim

Intervention Type BIOLOGICAL

tyrosinase peptide

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Eastern Cooperative Oncology Group

NETWORK

Sponsor Role lead

Principal Investigators

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John M. Kirkwood, MD

Role: STUDY_CHAIR

University of Pittsburgh

Locations

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CCOP - Scottsdale Oncology Program

Scottsdale, Arizona, United States

Site Status

Emory University Hospital - Atlanta

Atlanta, Georgia, United States

Site Status

Veterans Affairs Medical Center - Atlanta (Decatur)

Decatur, Georgia, United States

Site Status

Veterans Affairs Medical Center - Lakeside Chicago

Chicago, Illinois, United States

Site Status

Robert H. Lurie Comprehensive Cancer Center, Northwestern University

Chicago, Illinois, United States

Site Status

CCOP - Evanston

Evanston, Illinois, United States

Site Status

CCOP - Carle Cancer Center

Urbana, Illinois, United States

Site Status

Indiana University Cancer Center

Indianapolis, Indiana, United States

Site Status

Veterans Affairs Medical Center - Indianapolis (Roudebush)

Indianapolis, Indiana, United States

Site Status

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, United States

Site Status

CCOP - Wichita

Wichita, Kansas, United States

Site Status

CCOP - Ochsner

New Orleans, Louisiana, United States

Site Status

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Site Status

Tuft-New England Medical Center

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

CCOP - Kalamazoo

Kalamazoo, Michigan, United States

Site Status

CCOP - Northern New Jersey

Hackensack, New Jersey, United States

Site Status

Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status

Albert Einstein Clinical Cancer Center

The Bronx, New York, United States

Site Status

Ireland Cancer Center

Cleveland, Ohio, United States

Site Status

CCOP - Toledo Community Hospital

Toledo, Ohio, United States

Site Status

CCOP - Geisinger Clinic and Medical Center

Danville, Pennsylvania, United States

Site Status

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

Site Status

CCOP - Sioux Community Cancer Consortium

Sioux Falls, South Dakota, United States

Site Status

CCOP - Scott and White Hospital

Temple, Texas, United States

Site Status

Cancer Center at the University of Virginia

Charlottesville, Virginia, United States

Site Status

CCOP - St. Vincent Hospital Cancer Center, Green Bay

Green Bay, Wisconsin, United States

Site Status

Veterans Affairs Medical Center - Madison

Madison, Wisconsin, United States

Site Status

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

Site Status

CCOP - Marshfield Medical Research and Education Foundation

Marshfield, Wisconsin, United States

Site Status

Countries

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United States

References

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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 Aug 15;131(4):874-84. doi: 10.1002/ijc.26481. Epub 2012 Jan 11.

Reference Type RESULT
PMID: 22021080 (View on PubMed)

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 advanced metastatic melanoma: Eastern Cooperative Oncology Group Phase II Trial E1696. Clin Cancer Res. 2009 Feb 15;15(4):1443-51. doi: 10.1158/1078-0432.CCR-08-1231.

Reference Type RESULT
PMID: 19228745 (View on PubMed)

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 (368-376, 370D) (MGT) +/- IFNα2b and GM-CSF. [Abstract] J Clin Oncol 22 (Suppl 14): A-7502, 710s, 2004.

Reference Type RESULT

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. [Abstract] 22: A-2850, 709, 2003.

Reference Type RESULT

Other Identifiers

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E-1696

Identifier Type: -

Identifier Source: secondary_id

CDR0000068263

Identifier Type: -

Identifier Source: org_study_id