Ipilimumab in Combination With Androgen Suppression Therapy in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer
Condition: Adenocarcinoma of the Prostate; Hormone-resistant Prostate Cancer; Recurrent Prostate Cancer; Stage IV Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: ipilimumab; laboratory biomarker analysis
Intervention description: Given IV; Correlative studies
Intervention MeSH terms: Antineoplastic Agents, Immunological; Ipilimumab; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well ipilimumab works when given together with androgen
      suppression therapy in treating patients with hormone-resistant prostate cancer that has
      spread to other parts of the body. Monoclonal antibodies, such as ipilimumab, can block tumor
      growth in different ways. Some block the ability of tumors to grow and spread. Others find
      tumor cells and help kill them or carry tumor-killing substances to them. Androgen can cause
      the growth of prostate cancer. Androgen deprivation therapy may stop the adrenal glands from
      making androgen. Giving ipilimumab together with androgen suppression therapy may kill more
      tumor cells.
    

Eligibility criteria:

        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 x 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:

          -  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 or superficial bladder cancer

          -  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