Randomized, Double-Blind, Phase 3 Trial to Compare the Efficacy of Ipilimumab vs
Placebo in Asymptomatic or Minimally Symptomatic Patients with Metastatic
Chemotherapy-Naïve Castration Resistant Prostate Cancer

a) Histologic or cytologic confirmation of adenocarcinoma of the prostate: ;b) Have been treated by orchiectomy or are receiving a LH-RH analog, and have a testosterone level less than 50ng/dl: ;c) Metastatic disease by any 1 of the following modalities: CT, MRI, bone scan:;d) Progression during hormonal treatment. For eligibility purposes, progressive disease is defined as: ;i) Rising PSA values at a minimum of 1-week intervals and a 2.0 ng/ml minimum starting value
ii) Progression per bone scan: the appearance of 2 or more new lesions
iii) Progression per target lesions/measurable disease: nodal or visceral disease progression, per modified RECIST. Only lymph nodes greater than 2 cm will be considered to assess a change in size qualifying for disease progression. ;e) Anti-androgens (bicalutamide, flutamide, nilutamide) or adrenal androgen production inhibitors (aminoglutethamide or ketoconazole) should be discontinued prior to starting study therapy:
i) For subjects with a history of response to an anti-androgen or adrenal androgen production inhibitor and subsequent progression while on that anti-androgen should be assessed for anti-androgen withdrawal response for 4 weeks, and must demonstrate progression off anti-androgen prior to enrolment;
ii) For subjects that have never responded to anti-androgens, observation for anti-androgen withdrawal response is not necessary; however, a 2 week washout period is required prior to start of study therapy;f) ECOG Performance Status 0-1: ;g) Asymptomatic or minimally symptomatic.
i) Minimally symptomatic disease will be defined as the following:
(1) If cancer related pain is present, the pain must be rated by the patient as * 4 according to item #3 of the BPI-SF (*[on a scale of 0 to 10]...describe your pain at its worst in the last 24 hours.*) for all days during the 5 day assessment period prior to randomization;
(2) Any cancer related pain must not require any opiate analgesics (including codeine and dextropropoxyphene) over the 5 day assessment period prior to randomization.;h) Men > 18 years of age or minimum age of consent per local regulations.

1) Sexually active fertile men not using effective birth control if their partners are women of child-bearing potential (WOCBP). ;2) Visceral (liver, lung or brain) metastases are not permitted;;3) Medical History and Concurrent Diseases
a) Autoimmune disease: subjects with a documented history of inflammatory bowel disease, including ulcerative colitis and Crohn*s disease are excluded from this study.
Subjects with a history of symptomatic disease (eg, rheumatoid arthritis, autoimmune thyroiditis (eg, Hashimoto*s disease), autoimmune hepatitis, systemic progressive sclerosis (scleroderma), Systemic Lupus Erythematosus, autoimmune vasculitis (eg, Wegener*s Granulomatosis); Subjects with motor neuropathy considered of autoimmune origin (eg, Guillain-Barré Syndrome) are excluded from this study. Patients with vitiligo are eligible to enter the study.;b) Less than 1 year since resolution of * Grade 2 toxicity related to pelvic-targeted therapy (e.g radiation enteritis);;c) Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent or completing questionnaires; ;d) A serious uncontrolled medical disorder that, in the opinion of the investigator, would impair the ability of the subject to receive protocol therapy; ;e) Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured and needing no subsequent therapy, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the breast;;f) Known HIV or Hepatitis B or Hepatitis C infection. ;4) Physical and Laboratory Test Findings
a) Inadequate hematologic function defined by an absolute neutrophil count (ANC) < 1,500/mm3, a platelet count < 100,000/mm3, or a haemoglobin level < 9 g/dL; ;b) Inadequate hepatic function defined by a total bilirubin level * 2.5 times the upper limit of normal (ULN), AST and ALT levels * 2.5 times the ULN or * 5 times the ULN if liver metastases are present; ;c) Inadequate renal function defined by a serum creatinine level * 2.5 times the ULN; ;d) Inadequate creatinine clearance defined as less than 50 mL/min; ;5) Prohibited Treatments and/or Therapies
a) Prior treatment with any immunotherapy for prostate cancer, including autologous prostate cancer vaccine sipuleucel-T (Provenge®);;b) Prior or ongoing cytotoxic therapy for metastatic prostate cancer (eg, docetaxel,
mitoxantrone, estramustine);;c) Pelvic-targeted radiotherapy within 3 months prior to the start of study therapy;;d) Chronic use of immunosuppressants and/or systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses). However, during the course of the study, use of corticosteroids is allowed if used for treating irAEs, or adrenal insufficiencies; ;e) Any non-oncology vaccine therapy used for the prevention of infectious diseases (for up to 4 weeks prior to or after any dose of blinded study drug); ;f) Prior treatment with any inhibitor or agonist of T cell costimulation; ;g) Prior radioisotope therapy (e.g. strontium -89, samarium -153 or similar agents; ;6) Prisoners or subjects who are involuntarily incarcerated; ;7) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.