Ipilimumab in Combination With Androgen Suppression Therapy in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

Inclusion Criteria:

• Willing and able to give written informed consent
• Histologic diagnosis of adenocarcinoma of the prostate
• A PSA of > 0.2 ng/ml after 6-18 months of androgen suppression therapy, which may consist of luteinizing hormone-releasing hormone (LHRH) agonist or antagonist alone or the combination of an LHRH agonist or antagonist plus an antiandrogen, such as bicalutamide; androgen suppression therapy will continue without interruption
• Radiographic evidence of regional or distant metastasis at the time of study enrollment or at the time of diagnosis
• White blood cell (WBC) >= 2000/uL
• Absolute neutrophil count (ANC) >= 1000/uL
• Platelets >= 50 x 10^3/uL
• Hemoglobin >= 8 g/dL
• Creatinine =< 3.0 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 *ULN for patients without liver metastasis
• Bilirubin =< 3.0 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
• No known active or chronic infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; patients should be assessed for high risk behaviors that may result in these infections, such as intravenous drug use or multiple sexual partners; the assessment should be noted
• Eastern Cooperative Oncology Group (ECOG) =< 1
• Patients receiving any herbal product known to decrease PSA levels (i.e. saw palmetto and prostate cancer [PC]-SPES), or any immunosuppressive dose of systemic or absorbable topical corticosteroid (except prednisone up to 10 mg orally per [q] day, or its equivalent), must discontinue the agent for at least 2 weeks prior to screening; progressive disease must be documented after discontinuation of these products
• Patients receiving bisphosphonate therapy must have been on stable doses for at least 4 weeks with stable symptoms prior to the first infusion with ipilimumab
• Total testosterone < 50 ng/ml, except in patients with prior orchiectomy, where testosterone does not need to be measured; patients must continue their LHRH agonist therapy throughout study duration
• Life expectancy >= 6 months; this must be documented
• Patients who are sexually active with a partner who could become pregnant are to use an effective form of barrier contraception, such as condoms or a partner using oral contraceptive pills; persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 8 weeks after ipilimumab is stopped
• If a patient enters the trial on androgen suppression therapy (AST) that consists of both an LHRH agonist and an oral antiandrogen, both agents should be continued throughout the study; if an antiandrogen is stopped prior to study entry, it should be stopped 4 weeks before for nilutamide and flutamide and 6 weeks before for bicalutamide to ensure that a withdrawal phenomenon does not interfere with interpretation of efficacy results

Exclusion Criteria:

• Prior history of pelvic radiation associated with significant radiation proctitis within 12 months prior to planned first infusion of ipilimumab; for the purpose of this protocol, radiation proctitis is defined as diarrhea that reached a level of grade 2 or grade 3, that occurred within one month of radiation treatment, and that was of 7 days duration or longer
• Radiation to any area of the body < 28 days prior to randomization
• Any other active malignancy with the exception of adequately treated basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix
• Autoimmune disease: Patients with a history of inflammatory bowel disease are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Myasthenia Gravis, Guillain-Barre Syndrome); those with immune-mediated skin toxicity (i.e. Toxic Epidermal Necrolysis, Stevens-Johnson Syndrome) will also be excluded
• Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea
• Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab)
• A history of prior treatment with ipilimumab or prior cluster of differentiation (CD)137 agonist or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor or agonist
• Concomitant therapy with any of the following: Interleukin (IL)-2,interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents (over the counter [OTC]/herbal/prescribed); immunostimulant agents, other than the study agent; other investigational therapies; or chronic use of systemic corticosteroids (greater than prednisone 10 mg orally per day, or its equivalent)
• Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (i.e., infectious) illness