Sipuleucel-T, CT-011, and Cyclophosphamide for Advanced Prostate Cancer
Condition: Prostatic Neoplasms
MeSH terms: Prostatic Neoplasms
Intervention: CT-011 (Anti-PD1 Antibody); Sipuleucel-T (Provenge); Cyclophosphamide
Intervention description: Immune Enhancer; Vaccine; Low dose- Immune Enhancer
Intervention MeSH terms: Cyclophosphamide; Antibodies; Immunoglobulins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Anti PD-1 Monoclonal Antibody; Vaccine; Autologous Cellular Immunotherapy; Prostate Cancer

Summary:

      Background:

      - Sipuleucel-T is a new treatment for advanced stage prostate cancer. It takes cells from a
      person with prostate cancer and treats them in the laboratory. Then it returns the cells to
      the person to help the immune system fight the cancer. Sipuleucel-T may be combined with the
      drug CT-011 to boost its ability to kill cancer cells. The chemotherapy drug cyclophosphamide
      will also be given, either before or after the cells are collected at the start of the
      treatment.

      Objectives:

      - To test the effectiveness of Sipuleucel-T, CT-011, and cyclophosphamide for prostate
      cancer.

      Eligibility:

      - Men at least 18 years of age who have advanced prostate cancer.

      Design:

        -  Participants will be screened with a medical history, physical exam, blood and urine
           tests, and imaging studies.

        -  This study has two parts, with different participants in each part. All participants
           will be monitored with frequent blood tests and imaging studies.

        -  Part I:

        -  Participants will provide cells for the Sipuleucel-T treatment three times. The first
           time will be 3 days before the chemotherapy. The second time will be 10 days after
           chemotherapy. The third time will be 24 days after chemotherapy.

        -  Participants will have one dose of cyclophosphamide the day before the first dose of
           Sipuleucel-T.

        -  Participants will have Sipuleucel-T about 3 days after each cell donation.

        -  Part II:

        -  Participants will be in three groups: Sipuleucel-T given alone, given with CT-011, or
           given with both cyclophosphamide and CT-011.

        -  Participants will provide cells for the Sipuleucel-T treatment three times, as in Part
           I.

        -  Participants will have Sipuleucel-T about 3 days after each cell donation, and will
           receive treatment with the other drugs as directed by the study doctors.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Patients must have histopathological documentation of prostate cancer prior to starting
        this study.

        Patients must have metastatic progressive castrate-resistant prostate cancer defined as
        progressive disease (see below) despite surgical castration or ongoing use of
        gonadotropin-releasing hormone agonists with confirmed castrate levels of testosterone.
        Criteria of progression for trial eligibility are defined from the Prostate Cancer Clinical
        Trials Working Group-253. Clinically progressive prostate cancer must be evidenced and
        documented by any of the following parameters:

          1. Two consecutively rising PSA values at a minimum of 1-week intervals (2.0 ng/mL is the
             minimum starting value for PSA)

          2. Appearance of one or more new lesions on bone scans

          3. Progressive measurable disease by RECIST 1.1

             Patients on flutamide for at least 6 months must have disease progression at least 4
             weeks after withdrawal. Patients on bicalutamide or nilutamide for at least 6 months
             must have progression at least 6 weeks after withdrawal.2.1.1.4 Performance Status:
             ECOG 0-1 or Karnofsky 80-100% (asymptomatic or minimally symptomatic from metastatic
             disease).

             No previous chemotherapy use.

             No therapeutic immunosuppression or immunomodulation altering bone marrow function
             within 6 weeks prior to study entry e.g. G-CSF, GM-CSF, EPO, prednisone etc.

             Must have adequate:

               -  Bone marrow function: Absolute neutrophil count (ANC) greater than or equal to
                  1,500/mcl. Platelets greater than or equal to 100,000/mcl.

               -  Renal function: Creatinine less than or equal to 1.5 times institutional upper
                  limit normal (ULN)

               -  Hepatic function: Bilirubin less than or equal to 1.5 x ULN (CTCAE v4.0 grade 1)
                  except patients with Gilbert's disease (up to 5.0 mg/dL). SGOT and alkaline
                  phosphatase less than or equal to 2.5 x ULN.

               -  Normal Cardiac function: ECG with no evidence of arrhythmia, conduction
                  abnormality or ischemia. No active coronary artery disease; no New York Heart
                  Association class II, III or IV disease; no arrhythmia requiring treatment.

             Must willing and able to sign an informed consent document that explains the
             neoplastic nature of the disease, the procedures to be followed, the experimental
             nature of the treatment, alternative treatment and potential risks and toxicities.

             EXCLUSION CRITERIA:

             Concurrent treatment with any other cancer therapies including radiation (except
             palliative radiation therapy for bone metastases), chemotherapy or other
             investigational agent(s). Androgen suppression therapy will be allowed.

             History of a second active malignancy in the last 2 years other than non-melanoma skin
             cancers.

             Patients who have active or history of autoimmune disease/symptom/conditions
             including: type I diabetes, rheumatoid arthritis, systemic lupus erythematosus (SLE),
             ulcerative colitis, Crohn's Disease, multiple sclerosis (MS), ankylosing spondylitis.
             Type II diabetes mellitus, vitiligo or stable hypothyroidism are not considered
             exclusion criteria.

             Patients being chronically treated with immunosuppressive drugs such as cyclosporin,
             adrenocorticotropic hormone (ACTH).

             Concurrent use of systemic glucocorticoids within 4 weeks prior to trial entry

             Patients who have acquired, hereditary, or congenital immunodeficiencies including
             cellular immunodeficiencies, hypogammaglobulinemia and dysgammaglobulinemia.

             CNS, lung, or liver metastasis, because of the poor prognosis, and potential inability
             to meet study endpoints.

             Serious active infection at the time of pre-study screening.

             Positive HIV or Hepatitis C antibodies or Hepatitis B anti-core antibodies, because
             immunotherapies rely on intact immune systems, and toxicities may be exacerbated by
             the presence of infection.