The purpose of this study is to determine the safety and efficacy of MDX-010 (anti-CTLA4) in combination with MDX-1379 in patients with previously treated, unresectable Stage III or IV melanoma. Survival time will be evaluated, as well as patient responses and time to disease progression. Eligible patients are those who in response to a single regimen containing IL-2, dacarbazine, and/or temozolomide, have 1) relapsed following an objective response (PR/CR); 2) failed to demonstrate an objective response (PR/CR); or 3) could not tolerate such a regimen due to unacceptable toxicity. Patients will be randomized into one of three groups, and will receive one of the following treatments: MDX-010 alone, MDX-1379 alone, or MDX-010 in combination with MDX-1379.
Primary Outcome Measures:
- Best Objective Response Rate (BORR) [ Time Frame: BORR will be measure at 24 weeks ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Overall Survival [ Time Frame: all patients will be followed until a mortality rate of 75% in vaccine arm is reached ] [ Designated as safety issue: No ]
- Major durable response rate [ Time Frame: from baseline measurements through to patient completement ] [ Designated as safety issue: No ]
- duration of response [ Time Frame: from confirmation of response to confirmation of progression ] [ Designated as safety issue: No ]
- progression free survival [ Time Frame: measured from initial drug administration to time of progression ] [ Designated as safety issue: No ]
- time to progression [ Time Frame: from time of initial drug administration to confirmed progression ] [ Designated as safety issue: No ]
- health-related Quality of Life [ Time Frame: up to day 162 ] [ Designated as safety issue: No ]
| Estimated Enrollment: |
750 |
| Study Start Date: |
September 2004 |
| Estimated Study Completion Date: |
January 2009 |
| Estimated Primary Completion Date: |
January 2009 (Final data collection date for primary outcome measure) |
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1: Active Comparator
Melanoma Peptide Vaccine (MDX-1379) + Placebo
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Biological: MDX-1379 Melanoma Peptide Vaccine
2mL (2 subcutaneous injections of 1mL each, to each thigh), every 3 weeks for 4 doses.
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2: Experimental
MDX-010 + MDX-1379 (Melanoma Peptide Vaccine)
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Drug: MDX-010 (anti-CTLA4) monoclonal antibody
3mg/kg (iv infusion over 90 minutes), every 3 weeks for 4 doses
Biological: MDX-1379 Melanoma Peptide Vaccine
2mL (2 subcutaneous injections of 1mL each, to each thigh), every 3 weeks for 4 doses.
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3: Active Comparator
MDX-010 + Placebo
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Drug: MDX-010 (anti-CTLA4) monoclonal antibody
3mg/kg (iv infusion over 90 minutes), every 3 weeks for 4 doses
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Melanoma accounts for approximately 5% of all skin cancers in the United States, but it accounts for about 75% of all skin cancer deaths. In 2004, the expected prevalence of melanoma is 627,252, with about 119,178 of these cases being Stage III or IV (metastatic melanoma). First line treatments for metastatic melanoma, usually IL-2, dacarbazine and/or temozolomide, are associated with significant toxicities. MDX-010 (anti-CTLA4) antibodies are designed to keep the immune system running by blocking CTLA-4 from down-regulating T cell activation. MDX-1379 is made up of two peptides that are pieces of a bigger melanoma protein (gp100). These peptides bind to HLA-A2 which is then recognized by T cells.
Purpose
