Clinical trial NCT00006385: Vaccine Therapy With or Without Biological Therapy in Treating Patients With Metastatic Melanoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Melanoma (Skin)
Keywords: stage IV melanoma
recurrent melanoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: CCOP - Scottsdale Oncology Program
state: Arizona
city: Atlanta
country: United States
facility: Emory University Hospital - Atlanta
state: Georgia
city: Decatur
country: United States
facility: Veterans Affairs Medical Center - Atlanta (Decatur)
state: Georgia
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Lakeside Chicago
state: Illinois
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center, Northwestern University
state: Illinois
city: Evanston
country: United States
facility: CCOP - Evanston
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Veterans Affairs Medical Center - Indianapolis (Roudebush)
state: Indiana
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: New Orleans
country: United States
facility: CCOP - Ochsner
state: Louisiana
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Tuft-New England Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Kalamazoo
country: United States
facility: CCOP - Kalamazoo
state: Michigan
city: Hackensack
country: United States
facility: CCOP - Northern New Jersey
state: New Jersey
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey
state: New Jersey
city: Bronx
country: United States
facility: Albert Einstein Clinical Cancer Center
state: New York
city: Cleveland
country: United States
facility: Ireland Cancer Center
state: Ohio
city: Toledo
country: United States
facility: CCOP - Toledo Community Hospital
state: Ohio
city: Danville
country: United States
facility: CCOP - Geisinger Clinic and Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute
state: Pennsylvania
city: Sioux Falls
country: United States
facility: CCOP - Sioux Community Cancer Consortium
state: South Dakota
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: Charlottesville
country: United States
facility: Cancer Center at the University of Virginia
state: Virginia
city: Green Bay
country: United States
facility: CCOP - St. Vincent Hospital Cancer Center, Green Bay
state: Wisconsin
city: Madison
country: United States
facility: Veterans Affairs Medical Center - Madison
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Marshfield
country: United States
facility: CCOP - Marshfield Medical Research and Education Foundation
state: Wisconsin
Study officials:
affiliation: University of Pittsburgh
name: John M. Kirkwood, MD
role: STUDY_CHAIR
References:
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 Aug 15;131(4):874-84. doi: 10.1002/ijc.26481. Epub 2012 Jan 11.
citation: 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.
citation: 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.
citation: 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.