A Study of Sipuleucel-T With Administration of Enzalutamide in Men With Metastatic Castrate-Resistant Prostate Cancer
Condition: Metastatic Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: sipuleucel-T; enzalutamide
Intervention description: Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF).; Enzalutamide is an androgen receptor inhibitor. It is indicated for the treatment of patients with mCRPC who have previously received docetaxel. The enzalutamide dose used in this study will be 160 mg orally once daily.
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 52.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a randomized, open-label study designed to assess the effects of sipuleucel-T when
      administered concurrently or sequentially with enzalutamide.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent provided prior to the initiation of study procedures.

          -  Age ≥ 18 years.

          -  Histologically documented adenocarcinoma prostate cancer confirmed by a pathology
             report from prostate biopsy or a radical prostatectomy specimen.

          -  Metastatic disease as evidenced by bone metastasis or lymph node metastasis.

          -  Castrate-resistant prostate cancer as demonstrated by one of the following:

               -  Prostate specific antigen progression.

               -  Progression of measurable disease.

               -  Progression of non-measurable disease by soft tissue disease or bone disease.

          -  Castration levels of testosterone (≤ 50 ng/dL) achieved via medical or surgical
             castration.

          -  Serum PSA (Prostate specific antigen) ≥ 2.0 ng/mL.

          -  Screening ECOG (The Eastern Cooperative Oncology Group )performance status ≤ 1

          -  Adequate screening hematologic, renal, and liver function as evidenced by laboratory
             test results obtained ≤ 28 days prior to registration.

          -  Negative serology test for human immunodeficiency virus 1 and 2.

          -  Resides within driving distance (round trip within 1 day) of the clinical trial site
             for the duration of the active phase.

        Exclusion Criteria:

          -  The presence of known lung, liver, or brain metastases, malignant pleural effusions,
             or malignant ascites.

          -  Spinal cord compression, imminent long bone fracture, or any other condition that is
             likely to require radiation therapy and/or steroids for pain control during the active
             phase.

          -  History of stage 3 or greater cancer, excluding prostate cancer. Basal or squamous
             cell skin cancers must have been adequately treated and the subject must be disease
             free at the time of registration. Subjects with a history of stage 1 or 2 cancer must
             have been adequately treated and been disease free for ≥ 3 years at the time of
             registration.

          -  History of seizures or of predisposing factors for seizures.

          -  Child-Pugh Class C hepatic insufficiency.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to sipuleucel-T, GM-CSF or granulocyte colony stimulating factor (G-CSF).

          -  Previous treatment with sipuleucel-T or enrollment in a sipuleucel-T trial, regardless
             of whether the subject received sipuleucel-T or control.

          -  Previous treatment with enzalutamide.

          -  Previous treatment with abiraterone acetate.

          -  Previous treatment with ipilimumab.

          -  Previous treatment with ketoconazole other than topical use or for treatment of
             infections (e.g., oral thrush); most recent use must have been ≥ 7 days prior to
             registration.

          -  Previous treatment with any immunotherapy or investigational vaccine.

          -  A requirement for ongoing systemic immunosuppressive therapy. Use of inhaled,
             intranasal, intra-articular, and topical steroids is allowed. Oral or IV steroids to
             prevent or treat IV contrast reactions are allowed.

          -  Previous treatment with chemotherapy for mCRPC, or chemotherapy for any reason ≤ 2
             years prior to registration.

          -  Use of concomitant medications that may lower the seizure threshold or the use of
             antiseizure medications ≤ 1 year prior to registration.

          -  Received GM-CSF or G-CSF ≤ 90 days prior to registration.

          -  Ongoing non-steroidal antiandrogen withdrawal response.

          -  Any of the following medications or interventions ≤ 28 days prior to registration:

               -  Radiation therapy, either via external beam or brachytherapy.

               -  Any systemic steroid. Use of inhaled, intra-nasal, intra-articular, and topical
                  steroids is allowed. Oral or IV steroids to prevent or treat IV contrast
                  reactions are allowed.

               -  Any systemic therapy for prostate cancer, except for ADT (Androgen deprivation
                  therapy).

               -  Any investigational product for prostate cancer.

               -  Major surgery requiring general anesthesia, with the exception of placement of
                  central venous catheters.

               -  Inducers and inhibitors of cytochrome P450 (CYP) enzyme CYP2C8 (gemfibrozil and
                  rifampin).

               -  Medications that are metabolized by CYP3A4, CYP2C9, or CYP2C19 that have a narrow
                  therapeutic index.

               -  Inducers of CYP3A4 (including but not limited to phenytoin, carbamazepine,
                  rifampin, rifabutin, rifapentine, and phenobarbital).

          -  A requirement for treatment with opioid analgesics for cancer-related pain ≤ 21 days
             prior to registration.

          -  An active infection requiring parenteral antibiotic therapy or causing fever
             (temperature > 100.5˚ F or 38.1˚ C) ≤ 1 week prior to registration.

          -  Any medical intervention, any other condition, or any other circumstance which could
             compromise adherence with study requirements or otherwise compromise the study's
             objectives.