Monoclonal Antibody and Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma That Has Been Removed During Surgery

Sponsor

University of Southern California (Other)

Overall Status

Completed

CT.gov ID

NCT00025181

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Vaccines made from a person's cancer cells may make the body build an immune response to kill tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining monoclonal antibody therapy and vaccine therapy in treating patients who have stage III or stage IV melanoma that has been removed during surgery.

Condition or Disease	Intervention/Treatment	Phase
Intraocular Melanoma Melanoma (Skin)	Biological: MART-1 antigen Biological: gp100 antigen Biological: incomplete Freund's adjuvant Biological: ipilimumab Biological: tyrosinase peptide Procedure: adjuvant therapy	Phase 1

Detailed Description

OBJECTIVES:

Determine the safety and adverse event profile of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody combined with tyrosinase:368-376, gp100:209-217, and MART-1:26-35 peptides emulsified in Montanide ISA-51 in patients with resected stage III or IV melanoma.
Determine if this regimen causes antigen-specific T-cell activation in these patients.
Determine the clearance profile of this regimen in these patients.
Assess the development of host immune response in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-CTLA4).

Patients receive tyrosinase:368-376, gp100:209-217, and MART-1:26-35 peptides emulsified in Montanide ISA-51 subcutaneously followed by MDX-CTLA4 IV over 90 minutes at 0, 1, 2, 3, 4, 5, 8, and 11 months in the absence of disease progression or unacceptable toxicity.

Cohorts of at least 6 patients receive escalating doses of MDX-CTLA4 until the maximum tolerated dose is determined.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter until disease progression.

PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

19 participants

Primary Purpose:

Treatment

Official Title:

An Open-label Study Of MDX-CTLA4 In Combination With Tyrosinase/gp100/MART-1 Peptides Emulsified With Montanide ISA 51 In The Treatment Of Patients With Resected Stage III Or Stage IV Melanoma

Study Start Date :

Oct 1, 2001

Actual Primary Completion Date :

Jan 1, 2003

Actual Study Completion Date :

Jun 1, 2005

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed completely resected stage III or IV melanoma
Mucosal or ocular subtypes allowed
HLA-A2 positive
Positive staining of tumor tissue with antibody HMB-45 for gp100, tyrosinase, and/or MART-1
Failed (or ineligible for or refusal of) interferon alfa

PATIENT CHARACTERISTICS:

Age:

Not specified

Performance status:

Karnofsky 60-100%

Life expectancy:

At least 12 months

Hematopoietic:

WBC at least 2,500/mm^3
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Hemoglobin at least 10 g/dL
Hematocrit at least 30%

Hepatic:

Bilirubin no greater than upper limit of normal (ULN)
AST no greater than 1.25 times ULN
Hepatitis B surface antigen negative
Hepatitis C antibody nonreactive

Renal:

Creatinine less than 1.25 times ULN

Immunologic:

Antinuclear antibody (ANA) negative OR
If ANA positive, must be:
Antithyroglobulin antibody negative
Rheumatoid factor negative
Anti-LKM antibody negative
Anti-phospholipid antibody negative
Anti-islet cell antibody negative
Anti-neutrophil cytoplasmic antibody negative
HIV negative
No autoimmune disease (e.g., uveitis or autoimmune inflammatory eye disease)
No active infection
No hypersensitivity to tyrosinase:368-376, gp100:209-217, MART-1:26-35, or Montanide ISA-51

Other:

No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix
No underlying medical condition that would preclude study
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

See Disease Characteristics
No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody
No prior tyrosinase, gp100, or MART-1 peptide
No prior antitumor vaccination
No prior interleukin-2
At least 4 weeks since prior immunotherapy for melanoma

Chemotherapy:

At least 4 weeks since prior chemotherapy for melanoma

Endocrine therapy:

At least 4 weeks since prior hormonal therapy for melanoma
At least 4 weeks since prior corticosteroids
No concurrent systemic or topical corticosteroids

Radiotherapy:

At least 4 weeks since prior radiotherapy for melanoma

Surgery:

See Disease Characteristics

Other:

No prior cytotoxic therapy
At least 4 weeks since any other prior therapy for melanoma
Concurrent analgesics allowed if on stable dose for at least 2 weeks before study