MDX-010 Antibody, MDX-1379 Melanoma Vaccine, or MDX-010/MDX-1379 Combination Treatment for Patients With Melanoma - Full Text View

Sponsored by:	Medarex
Information provided by:	Medarex
ClinicalTrials.gov Identifier:	NCT00094653

Purpose

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.

Condition	Intervention	Phase
Melanoma Metastases	Drug: MDX-010 (anti-CTLA4) monoclonal antibody Biological: MDX-1379 Melanoma Peptide Vaccine	Phase III

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Immunoglobulins Globulin, Immune Ipilimumab Cytotoxic T-lymphocyte antigen 4

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	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

Further study details as provided by Medarex:

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)

Arms	Assigned Interventions
1: Active Comparator Melanoma Peptide Vaccine (MDX-1379) + Placebo	Biological: MDX-1379 Melanoma Peptide Vaccine 2mL (2 subcutaneous injections of 1mL each, to each thigh), every 3 weeks for 4 doses.
2: Experimental MDX-010 + MDX-1379 (Melanoma Peptide Vaccine)	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.
3: Active Comparator MDX-010 + Placebo	Drug: MDX-010 (anti-CTLA4) monoclonal antibody 3mg/kg (iv infusion over 90 minutes), every 3 weeks for 4 doses

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00094653

Show 211 Study Locations

Sponsors and Collaborators

Medarex

Investigators

Study Director:

Michael Yellin, MD

Medarex

More Information

Responsible Party:	Medarex, Inc. ( Michael Yellin, Senior Director, Clinical Science )
Study ID Numbers:	MDX010-20
Study First Received:	October 21, 2004
Last Updated:	November 3, 2008
ClinicalTrials.gov Identifier:	NCT00094653
Health Authority:	United States: Food and Drug Administration

Keywords provided by Medarex:

melanoma
metastatic melanoma
skin cancer

Study placed in the following topic categories:

Skin Neoplasms
Cytotoxic T-lymphocyte antigen 4
Melanoma
Neuroendocrine Tumors
Antibodies, Monoclonal
Neuroectodermal Tumors
Antibodies

Neoplasms, Germ Cell and Embryonal
Nevus, Pigmented
Neoplasm Metastasis
Neuroepithelioma
Nevus
Immunoglobulins

Additional relevant MeSH terms:

Neoplastic Processes
Neoplasms
Pathologic Processes
Neoplasms by Histologic Type
Immunologic Factors

Physiological Effects of Drugs
Neoplasms, Nerve Tissue
Nevi and Melanomas
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009