Study of MDX-010 in Patients With Metastatic Hormone-Refractory Prostate Cancer (MDX010-21)

• The primary objectives of the study are to determine the safety profile;
• maximum tolerated dose (MTD);
• and dose-limiting toxicity (DLT) of escalating doses of MDX-010 administered every 3 weeks up to 4 times to patients with HRPC.

• Provide a preliminary assessment of clinical antitumor activity, including an assessment of prostate-specific antigen (PSA) responses and metabolic bone activity. [ Time Frame: every 12 weeks ] [ Designated as safety issue: No ]
• Determine whether additional dosing in patients with mixed response or stable disease can elicit an objective response [ Time Frame: every 12 weeks ] [ Designated as safety issue: No ]

Multicenter study in which patients with metastatic hormone refractory prostate cancer (HRPC), who have not had previous chemotherapy or immunotherapy treatments, will receive MDX-010 every 3 weeks for 4 doses (12 weeks total duration). MDX-010 will be administered at escalating dosage levels of 3, 5, 7.5 and 10 mg/kg/dose infusions. At least 6 patients will be enrolled in each dosage level. Patients will be followed for 1 year or until disease progression to assess response. Patients will be followed for survival status for up to 7 years after enrollment. Patients who tolerate and respond to treatment or who have stable disease for 3 months or longer and who subsequently progress during the follow up phase of the study may have the option to receive additional treatment with MDX-010.

• Prostate Cancer
• Neoplasm Metastasis

Inclusion Criteria:

• Histologic diagnosis of adenocarcinoma of the prostate
• Metastatic prostate cancer (positive bone scan or measurable disease)
• Total testosterone of greater than 50 ng/dL, except for patients with prior orchiectomy, where testosterone does not need to be measured.
• Patients who are receiving an antiandrogen as part of primary androgen ablation must demonstrate disease progression following discontinuation of antiandrogen and completion of a washout period and then observe disease progression.
• Patients must stop using any herbal product known to decrease PSA levels (eg., saw palmetto and PC-SPES) or any systemic or topical corticosteroid at least 4 weeks prior to screening. Progressive disease must be documented after discontinuation of these products.
• Progressive disease after androgen deprivation (or hormone therapy). For patients with measurable disease, progression will be defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. For patients with progression in, or without any measurable disease, a positive bone scan and elevated PSA will be required.
• Patients receiving bisphosphate therapy must have been on stable doses for at least 4 weeks with stable symptoms prior to enrollment.
• No prior chemotherapy or immunotherapy (tumor vaccine, cytokine, or growth factor given to control prostate cancer).
• Prior radiation therapy completed at least 4 weeks prior to enrollment. No prior radiopharmaceuticals (strontium, samarium) within 8 weeks prior to enrollment.

Exclusion Criteria:

• Bone pain due to metastatic bone disease severe enough to require routine narcotic analgesic use.
• History of severe hypersensitivity reactions to drugs formulated with polysorbate 80.
• Patients with active autoimmune disease or a history of autoimmune disease that required systemic steroids or immunosuppressive medications, except for patients with vitiligo.
• Prior therapy with any anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) antibody.
• Active infection requiring therapy.
• Concurrent medical condition requiring the use of systemic or topical corticosteroids; systemic or topical corticosteroids must be discontinued at least 4 weeks prior to enrollment. The use of inhaled corticosteroids is acceptable.