A total of 108 males with advanced prostate cancer will be enrolled into this study. Patients must have undergone prostate cancer staging within 180 days of enrollment. 54 patients will be randomized to receive hormone therapy alone and 54 patients will be randomized to receive hormone therapy plus the MDX-010 therapy.

This trial has been designed to ensure the capture of both treatment mechanism-specific data as well as clinically meaningful data within a relatively compressed study interval. Thus, this trial is constructed around a single inductive short-term cycle of AA therapy.

• Drug: Combination Androgen Ablative Therapy

  Lupron 7.5 mg monthly times 3 months (leuprolide acetate)

  Casodex 50 mg daily times 3 months (Bicalutamide)

  Other Names:

  • Lupron or leuprolide acetate
  • Casodex or Bicalutamide
• Biological: MDX-010 therapy
  MDX-010 3 mg/kg one time dose (Ipilimumab)
  Other Name: MDX-010 or Ipilimumab

• 1: Experimental
  3 months of concurrent androgen ablative (AA) therapy + MDX-010
  Interventions:

  • Drug: Combination Androgen Ablative Therapy
  • Biological: MDX-010 therapy
• 2: Active Comparator
  3 months of initial AA therapy alone
  Intervention: Drug: Combination Androgen Ablative Therapy

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the prostate staged within 180 days of study enrollment, stage with or without metastatic disease, with the exclusion of central nervous system metastases; includes post radical prostatectomy patients with a rising PSA.
• An initial PSA greater than 4.0 using the Hybritech Assay. For those participants who have received hormone therapy less than or equal to 21 days, a documented PSA of greater than or equal to 4.0 prior to initiation of hormone therapy is acceptable. For those participants who are post radical prostatectomy, a rising PSA is acceptable.
• Adequate organ function defined as: WBC greater than 3,000; platelets greater than 75,000; total bilirubin less than 1.5mg; transaminases less than 2.5 times upper limit of normal; serum creatinine less than 2.0 mg or calculated creatinine clearance greater than 60 mL. All values must be obtained 14 days prior to study entry.
• ECOG performance status of 0 2.
• Patients must be 18 years of age at the time of study entry and able to understand and sign informed consent.

Exclusion Criteria:

• Underlying other serious medical condition which, in the opinion of the investigator, precludes study participation. This includes immuno-suppressive disease such as AIDS or autoimmune disorders such as multiple sclerosis or lupus.
• Patients not recovered from major infections and/or surgical procedures.
• Prior hormonal therapy greater than 21 days prior to enrollment, including estrogens, LH/RH agonists, antiandrogens, or 5-reductase inhibitors.
• Recent less than 3 months of informed consent usage of immuno suppressive medications including steroids, Immuran, Cyclosporin. Topical or inhalational steroid use is permissible.
• For participants who elect to undergo the baseline transrectal needle biopsy of the prostate, current usage of systemic anticoagulation therapy, i.e. heparin or coumadin or inability to discontinue aspirin, aspirin-containing products or ibuprofen for seven days prior to the prostate biopsies required for this study.
• Prior systemic chemotherapy.
• Prior radiation therapy to the prostate
• Concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer.
• Prior malignancy, unless the patient has been cancer free for five years or more.
• Uncontrolled underlying medical or psychiatric illness, or serious active infections.
• Patient unwilling to complete all required follow-up visits.

• Department of Defense
• U.S. Army Medical Research Acquisition Activity
• Medarex