Monoclonal Antibody and Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma That Has Been Removed During Surgery
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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 |
| 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) |
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 |
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| United States, California | |
| USC/Norris Comprehensive Cancer Center and Hospital | |
| Los Angeles, California, United States, 90089 | |
| Study Chair: | Jeffrey S. Weber, MD, PhD | USC/Norris Comprehensive Cancer Center |
More Information
Additional Information:
No publications provided
| Responsible Party: | USC/Norris Comprehensive Cancer Center |
| 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 USC/Norris Comprehensive Cancer Center:
|
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 Adjuvants, Immunologic Freund's Adjuvant Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 19, 2013