Ipilimumab + Androgen Depravation Therapy in Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Ipilimumab; Leuprolide; Goserelin; Degarelix
Intervention description: 10 mg/kg by vein over 90 minutes once every 4 weeks, for 4 weeks.; 7.5 mg intramuscular once a month for 8 months; 3.6 mg subcutaneous once a month for 8 months; 80 mg subcutaneous once a month for 8 months
Intervention MeSH terms: Ipilimumab; Leuprolide; Goserelin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Prostate cancer; Castrate sensitive prostate carcinoma; Metastatic prostate carcinoma; Androgen depravation therapy; ADT; Prostate-specific antigen; PSA; Ipilimumab; Yervoy; BMS-734016; MDX010; Leuprolide; Lupron Depot; Leuprolide Acetate; Goserelin; Zoladex; Degarelix; Firmagon

Summary:

      The goal of this clinical research study is to learn if ipilimumab in combination with either
      Lupron® (leuprolide), Zoladex® (goserelin), or Firmagon® (degarelix) can affect
      prostate-specific antigen (PSA) levels in patients with prostate cancer. Researchers also
      want to learn if these drug combinations affect the body's immune system. The safety of these
      drug combinations will also be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically or cytologically confirmed prostate carcinoma.

          2. Evidence of metastatic disease on previous bone scan and/or CT scan and/or MRI.

          3. Castrate-sensitive disease. Patients already on ADT are eligible as long as the time
             from initiation of LHRH analog or antagonist is not greater than 1 month AND the total
             exposure time to the LHRH analog or antagonist will not exceed 8 months (i.e. the
             effectiveness of current depot LHRH analog or antagonist does not extend beyond 8
             months since its initiation).

          4. Patients who have received prior hormonal therapy are allowed to participate as long
             as they have been off hormone ablation for 1.5 times as long as they were on it: e.g.
             1) Patients who have received up to 4 months of hormonal ablation are eligible as long
             as they have been off hormonal ablation for >/= 6 months; 2) Patients who have
             received 1 year of hormonal ablation are eligible as long as they have been off
             hormone ablation for >/= 18 months; 3) Patients who have received up to 2 years of
             hormonal ablation are eligible as long as they have been off hormonal ablation for >/=
             3 years have elapsed since its discontinuation.

          5. Eastern Cooperative Oncology Group (ECOG) performance status </= 1

          6. Patients must have normal organ and marrow function as defined below: a) white blood
             cell count (WBC) >/= 3000/uL; b) Absolute neutrophil count (ANC) >/= 1500/uL; c)
             Platelets >/= 100 x 10^3/uL; d) Hemoglobin >/= 9 g/dL; e) Creatinine </= 2mg/dL; f)
             ALT </= 2.5 x upper limit of normal (ULN) for patients without liver metastases. For
             patients with liver metastasis ALT </= 5 x ULN is allowed; g) Bilirubin </= 3 x ULN
             (except for patients with Gilbert's Syndrome, who must have a total bilirubin </=
             3mg/dL)

          7. Patients included in the study must be >/= 18 years old

          8. Ability to understand and willingness to sign a written informed consent document.

        Exclusion Criteria:

          1. Autoimmune disease: Patients with a history of inflammatory bowel disease (including
             Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid
             arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus
             or autoimmune vasculitis [e.g., Wegener's Granulomatosis] are excluded from this
             study.

          2. Any underlying medical or psychiatric condition, which in the opinion of the
             Investigator, will make the administration of study drug hazardous or obscure the
             interpretation of AEs: e.g. a condition associated with frequent diarrhea or chronic
             skin conditions, recent surgery or colonic biopsy from which the patient has not
             recovered, or partial endocrine organ deficiencies.

          3. Patients with known brain metastases.

          4. Patients with small cell carcinoma of the prostate.

          5. History of other malignancies, other than nonmelanoma skin cancer or Ta or T1 (low
             grade) bladder carcinomas, unless in complete remission and off therapy for that
             disease for at least 5 years.

          6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, history of congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          7. Known HIV, Hepatitis B, or Hepatitis C.

          8. Untreated symptomatic spinal cord compressions.

          9. Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to
             one month prior to or after any dose of ipilimumab).

         10. Concomitant therapy with any of the following: IL-2, interferon or other non-study
             immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other
             investigation therapies; or chronic use of systemic corticosteroids (used in the
             management of cancer or non-cancer-related illnesses).

         11. Previous participation in another ipilimumab clinical trial or prior treatment with a
             CD137 agonist or CTLA-4 inhibitor or agonist.

         12. History of acute diverticulitis, intra-abdominal abscess, GI obstruction, abdominal
             carcinomatosis or other known risk factors for bowel perforation.

         13. Patients who do not agree to practice appropriate birth control methods while on
             therapy.

         14. Concurrent use of 5-alpha reductase inhibitors (finasteride or dutasteride).