Clinical Trials /

Sipuleucel-T With Immediate vs. Delayed Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) Blockade for Prostate Cancer



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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Active, not recruiting


Phase 2

Trial Eligibility



  • Brief Title: Sipuleucel-T With Immediate vs. Delayed Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) Blockade for Prostate Cancer
  • Official Title: A Randomized Phase 2 Trial of Immediate vs. Delayed Anti-CTLA4 Blockade Following Sipuleucel-T Treatment for Prostate Cancer Immunotherapy

Clinical Trial IDs

  • ORG STUDY ID: 12557
  • SECONDARY ID: NCI-2014-00318
  • NCT ID: NCT01804465


  • Prostate Cancer


SipT TreatmentProvengeDelayed IpilimumabTreatment
IpilimumabBMS-734016/MDX-010, anti-CTLA4Delayed IpilimumabTreatment


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.

Detailed Description

      This is an open-label randomized multicenter Phase 2 clinical trial combining SipT with
      ipilimumab in patients with chemotherapy-naïve metastatic castration resistant prostate
      cancer (CRPC).

      All patients will be treated with standard SipT (Q2wks x 3). Patients will be randomized to
      one of two arms:

      Arm 1 (Immediate Treatment): Ipilimumab Q3wks x 4 started 1 day following the final dose of
      SipT (Day 0).

      Arm 2 (Delayed Treatment): Ipilimumab Q3wks x 4 started 3 weeks following the final dose of
      SipT (Day 0).

      Following this ipilimumab treatment, patients will then be followed monthly for 3 months and
      then quarterly until disease progression. The definition of unacceptable toxicity is grade 3
      or higher treatment-related toxicities (NCI CTCAE v4) excluding immune-related adverse events
      (irAEs). The study will assess for the immunogenicity and clinical activity of sequential
      sipuleucel-T treatment followed by ipilimumab. Patients who experience an initial clinical
      response to ipilimumab followed by subsequent disease progression will be offered reinduction
      treatment with ipilimumab.

Trial Arms

Immediate IpilimumabTreatmentExperimentalArm 1 (Immediate Treatment) Ipilimumab Q3wks x 4 started 1 day following the final dose of SipT.
  • SipT Treatment
  • Ipilimumab
Delayed IpilimumabTreatmentExperimentalArm 2 (Delayed Treatment) Ipilimumab Q3wks x 4 started 3 weeks following the final dose of SipT.
  • SipT Treatment
  • Ipilimumab

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 PSA Working Group 2
             and/or RECIST criteria. Patients must have disease progression by one or both of the

               -  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 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

               -  Inflammatory bowel disease, celiac disease, primary biliary cirrhosis, autoimmune

               -  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 AEs, 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.
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Impact of the timing of ipilimumab administration on prostatic acid phosphatase (PAP) / PAP fusion protein (PA2024) specific immune responses by SipT
Time Frame:Up to 20 weeks
Safety Issue:
Description:To assess the impact of the timing of ipilimumab treatment on the induction of immunoglobulin (IG) antibody responses by SipT, the proportion of patients on each study arm who achieve an immune response to PAP and/or PA2024 at study week 20 will be determined.

Secondary Outcome Measures

Measure:Prostate Specific Antigen (PSA) Measurements (patient response to therapy)
Time Frame:Up to 3 weeks
Safety Issue:
Description:Patient response in this study is defined as a PSA decline
Measure:Radiographic Clinical Responses
Time Frame:Up to 6 months
Safety Issue:
Measure:Modulation of Effector and Regulatory T Cells
Time Frame:Up to 20 weeks
Safety Issue:
Measure:Safety assessment of combining ipilimumab with SipT
Time Frame:up to 3 weeks
Safety Issue:
Description:Number of subjects with each toxicity and adverse event (AE) graded according to CTCAE v4 as well as immune related AEs


Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of California, San Francisco

Trial Keywords

  • castration resistant
  • prostate
  • cancer
  • ipilimumab
  • provenge
  • SipT

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