| MDX-010 Antibody, MDX-1379 Melanoma Vaccine, or MDX-010/MDX-1379 Combination Treatment for Patients With Melanoma |
| A Randomized, Double-Blind, Multicenter Study Comparing MDX-010 Monotherapy, MDX-010 in Combination With a Melanoma Peptide Vaccine, and Melanoma Vaccine Monotherapy in HLA-A2*0201-Positive Patients With Previously Treated Unresectable Stage III or IV Melanoma |
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. |
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. |
| Phase III |
| Interventional |
| Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study |
| Best Objective Response Rate (BORR) [ Time Frame: BORR will be measure at 24 weeks ] [ Designated as safety issue: No ] |
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 ] |
Melanoma
Metastases |
Drug: MDX-010 (anti-CTLA4) monoclonal antibody
Biological: MDX-1379 Melanoma Peptide Vaccine |
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| Recruiting |
| 750 |
| September 2004 |
| January 2009 |
Inclusion Criteria:
- Diagnosed with malignant melanoma
- Measurable unresectable Stage III or IV melanoma
- At least 18 years old
- HLA-A*0201 positive
- Previous treatment with & failure/relapse/inability to tolerate IL-2, dacarbazine and/or temozolomide
- At least 4 weeks since prior treatment
- Negative pregnancy
- Life expectancy greater than 4 months
- ECOG performance of 0 or 1
- Required lab values
- HIV, HBV, HCV negative
Exclusion Criteria:
- Prior malignancies which the patient has not been disease free for 5 years, except treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or any other cancer
- Ocular melanoma
- Active, untreated CNS metastasis
- Prior treatment with MDX-010 (anti-CTLA4) antibody
- Prior treatment with any cancer therapeutic vaccine
- Active autoimmune disease or history of autoimmune disease
- Pregnancy or nursing
- Hypersensitivity to Incomplete Freund's Adjuvant (IFA) (Montanide ISA-51)
- Underlying medical conditions deemed hazardous if treated with study drug
- Concomitant therapy with anti-melanoma drugs, chemotherapies, other investigational therapies, chronic use of systemic corticosteroids
- Unable to provide informed consent
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| Both |
| 18 Years and older |
| No |
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| United States, Argentina, Belgium, Brazil, Canada, Chile, France, Germany, Hungary, Netherlands, South Africa, Switzerland, United Kingdom |
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| NCT00094653 |
| MDX010-20 |
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| Medarex |
|
| Study Director: |
Michael Yellin, MD |
Medarex |
|
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| Medarex |
| February 2008 |
| October 21, 2004 |
| July 2, 2008 |
