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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Southern California
ClinicalTrials.gov Identifier:
NCT00025181
First received: October 11, 2001
Last updated: October 20, 2012
Last verified: October 2012
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by University of Southern California:

Enrollment: 19
Study Start Date: October 2001
Study Completion Date: June 2005
Primary Completion Date: January 2003 (Final data collection date for primary outcome measure)
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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00025181

Locations
United States, California
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90089
Sponsors and Collaborators
University of Southern California
Investigators
Study Chair: Jeffrey S. Weber, MD, PhD University of Southern California
  More Information

Additional Information:
No publications provided

Responsible Party: University of Southern California
ClinicalTrials.gov Identifier: NCT00025181     History of Changes
Other Study ID Numbers: CDR0000068934 (10M-00-4), LAC-USC-10M004, MDX-MDXCTLA4-03, NCI-4210
Study First Received: October 11, 2001
Last Updated: October 20, 2012
Health Authority: United States: Federal Government

Keywords provided by University of Southern California:
iris melanoma
ciliary body and choroid melanoma, small size
ciliary body and choroid melanoma, medium/large size
extraocular extension melanoma
recurrent intraocular melanoma
stage III melanoma
stage IV melanoma
recurrent melanoma

Additional relevant MeSH terms:
Melanoma
Uveal Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Eye Neoplasms
Neoplasms by Site
Eye Diseases
Uveal Diseases
Antibodies, Monoclonal
Freund's Adjuvant
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on April 23, 2014