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

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.