Vaccine Therapy With or Without Biological Therapy in Treating Patients With Metastatic Melanoma - Full Text View

Sponsor:	Eastern Cooperative Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00006385

Purpose

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	Intervention	Phase
Melanoma (Skin)	Biological: MART-1 antigen Biological: gp100 antigen Biological: incomplete Freund's adjuvant Biological: recombinant interferon alfa Biological: sargramostim Biological: tyrosinase peptide	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Interferon alfa-2a Granulocyte-macrophage colony-stimulating factor Sargramostim Interferon alfa-n1 Tyrosinase Freund's adjuvant Interferons

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:	September 2000
Primary Completion Date:	October 2006 (Final data collection date for primary outcome measure)

Detailed 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006385

Show 32 Study Locations

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

John M. Kirkwood, MD

UPMC Cancer Centers

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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-{alpha}2b in Advanced Metastatic Melanoma: Eastern Cooperative Oncology Group Phase II Trial E1696. Clin Cancer Res. 2009 Feb 15;15(4):1443-51.

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.

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.

Study ID Numbers:	CDR0000068263, E-1696
Study First Received:	October 4, 2000
Last Updated:	July 29, 2009
ClinicalTrials.gov Identifier:	NCT00006385 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage IV melanoma
recurrent melanoma

Additional relevant MeSH terms:

Anti-Infective Agents
Interferon Type I, Recombinant
Immunologic Factors
Antineoplastic Agents
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Melanoma
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses
Nevi and Melanomas
Angiogenesis Modulating Agents
Growth Inhibitors
Interferon-alpha

Neoplasms by Histologic Type
Growth Substances
Interferons
Adjuvants, Immunologic
Antiviral Agents
Angiogenesis Inhibitors
Pharmacologic Actions
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms
Freund's Adjuvant
Interferon Alfa-2a

ClinicalTrials.gov processed this record on November 27, 2009