A Study of Sipuleucel-T With Administration of Enzalutamide in Men With Metastatic Castrate-Resistant Prostate Cancer

This is a randomized, open-label study designed to assess the effects of sipuleucel-T when administered concurrently or sequentially with enzalutamide. This study consists of 3 phases. The screening phase will begin at the completion of the informed consent process and continue through registration. The active phase will begin at registration and continue through the post-treatment visit (30 to 37 days following the last study treatment). The long term follow-up (LTFU) phase will begin after the post-treatment visit and will continue until the subject's death or until Dendreon terminates the study.

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.