Sipuleucel-T With Immediate vs. Delayed Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) Blockade for Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: SipT Treatment; Ipilimumab
Intervention description: All patients will receive standard of care SipT treatment every two weeks for a total of 3 treatments. The three treatments usually take about 30 days to complete.
SipT treatment is given in three 1 hour infusions. Each SipT treatment is generated from a standard blood cell-collection procedure (called leukapheresis) performed 2-3 days prior to the infusion.; Ipilimumab will be given by IV over 90 minutes every 3 weeks. Patients will be monitored during the infusion and up to 1 hour post-infusion.
Intervention MeSH terms: Ipilimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: castration resistant; prostate; cancer; ipilimumab; provenge; SipT

Summary:

      The purpose of this study is to find out what effects taking ipilimumab, as an immediate or
      delayed treatment, following completion of sipuleucel-T (SipT) treatment, has on patients and
      their prostate cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically confirmed, metastatic prostate adenocarcinoma (positive bone scan
             and/or measurable disease on CT scan and/or MRI of the abdomen and pelvis).

          2. Progressive disease after androgen deprivation, as defined by Prostate Cancer Clinical
             Trials Working Group 2 (PCWG2) and/or RECIST criteria. Patients must have disease
             progression by one or both of the following:

               -  For patients with measurable disease, progression is defined as at least a 20%
                  increase in the sum of the longest diameter (LD) of target lesions or the
                  appearance of one or more new lesions, as per RECIST criteria version 1.1.

               -  For patients with no measurable disease, a positive bone scan and elevated
                  prostate specific antigen (PSA) will be required. PSA evidence for progressive
                  prostate cancer consists of a PSA level of at least 2 ng/milliliter (mL), which
                  has risen on at least 2 successive occasions, at least 1 week apart. If the
                  confirmatory PSA value is not greater than the screening PSA value, then an
                  additional test for rising PSA will be required to document progression.

               -  If no prior orchiectomy has been performed, patients must remain on luteinizing
                  hormone-releasing hormone (LHRH) agonist or antagonist (e.g. degarelix) therapy.
                  Patients who are receiving an antiandrogen as part of primary androgen ablation
                  must demonstrate disease progression following discontinuation of the
                  antiandrogen, defined as two consecutive rising PSA values, obtained at least two
                  weeks apart, or documented osseous or soft tissue progression. At least one of
                  the PSA values must be obtained at least four weeks (flutamide) or six weeks
                  (bicalutamide or nilutamide) after discontinuation.

          3. Laboratory requirements:

               -  Absolute neutrophil count (ANC) ≥ 1500/μL

               -  Bilirubin < 1.5 x upper limit of normal (ULN)

               -  Hemoglobin ≥ 8 g/dL

               -  PSA ≥ 2 ng/mL

               -  Platelets ≥ 100,000/μL

               -  aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or
                  equal to 2.5 x ULN

               -  Creatinine clearance ≥ 60 mL/min by the Cockcroft Gault equation

               -  Testosterone less than or equal to 50 ng/dL

          4. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1 and life expectancy
             ≥ 12 weeks.

          5. At least 18 years of age or older.

          6. Patients receiving any other hormonal therapy, including any dose of megestrol acetate
             (Megace), Proscar (finasteride), any herbal product known to decrease PSA levels (e.g.
             Saw Palmetto, PC-SPES), or any systemic corticosteroid, must discontinue the agent for
             at least four weeks prior to study treatment. Progressive disease as defined above
             must be documented after discontinuation of any hormonal therapy (with the exception
             of a LHRH agonist).

          7. Prior radiation therapy must be completed ≥ 4 weeks prior to enrollment and the
             patient must have recovered from all toxicity. Prior radiopharmaceuticals (strontium,
             samarium) must be completed ≥ 8 weeks prior to enrollment.

          8. Because of the unknown potential risk to a gamete and/or developing embryo from these
             investigational therapies, patients must agree to use adequate contraception (barrier
             method for males) for the duration of study participation, and for three months after
             discontinuing therapy.

        Exclusion Criteria:

          1. Prior chemotherapy for prostate cancer, with the exception of neoadjuvant
             chemotherapy, because of the potential effect of chemotherapy on the immune system.

          2. Prior sipuleucel-T treatment or investigational immunotherapy.

          3. Prostate cancer pain requiring regularly scheduled narcotics.

          4. Current treatment with systemic steroid therapy (inhaled/topical steroids are
             acceptable). Systemic corticosteroids must be discontinued for at least 4 weeks prior
             to first treatment.

          5. History of autoimmune disease including, but not limited to:

               -  Systemic lupus erythematosis (SLE), scleroderma, CREST syndrome, rheumatoid
                  arthritis

               -  Inflammatory bowel disease, celiac disease, primary biliary cirrhosis, autoimmune
                  hepatitis

               -  Dermatomyositis, polymyositis, giant cell arteritis

               -  Autoimmune hemolytic anemia (AIHA), cryoglobulinemia, antiphospholipid antibody
                  syndrome (APLS)

               -  Diabetes mellitus type I, myasthenia gravis, Grave's disease

               -  Wegener's granulomatosis or other vasculitis

               -  A history of Hashimoto's thyroiditis, psoriasis, or eczema, any of which has been
                  inactive for at least one year, or isolated Raynaud's phenomenon is acceptable

          6. Known central nervous system or visceral metastases.

          7. Medical or psychiatric illness that would, in the opinion of the investigator,
             preclude participation in the study or the ability of patients to provide informed
             consent for themselves.

          8. Cardiovascular disease that meets one of the following: congestive heart failure (New
             York Heart Association Class III or IV), active angina pectoris, or recent myocardial
             infarction (within the last 6 months).

          9. Concurrent or prior malignancy except for the following:

               -  Adequately treated basal or squamous cell skin cancer

               -  Adequately treated stage I or II cancer from which the patient is currently in
                  complete remission

               -  Any other cancer from which the patient has been disease-free for 5 years

         10. Known HIV or other history of immunodeficiency disorder.

         11. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
             treatment of either a psychiatric or medical (e.g. infectious) illness.

         12. 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 (AE), such as a condition associated with frequent
             diarrhea.

         13. A history of prior treatment with ipilimumab or prior cluster of differentiation 137
             (CD137) agonist or CTLA-4 inhibitor or agonist.