Docetaxel/Prednisone Versus Docetaxel/Prednisone and Enzalutamide in Castration-Resistant Prostate Cancer

Inclusion Criteria: * Willing and able to provide written informed consent and HIPAA authorization for the release of personal health information. NOTE: HIPAA authorization may be either included in the informed consent or obtained separately. * Males 18 years of age and above * Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features * Having documented disease progression on enzalutamide defined by 1 or more of the following criteria: * PSA progression according to PCWG2 criteria with 3 consecutive rising PSA measurements, all collected at least 1 week apart * Radiographic progression in soft tissue or bone by modified RECIST 1.1 for subjects with measurable disease; or * Bone disease progression defined by 2 or more new lesions on 2 consecutive bone scans in the absence of falling PSA * Patients who have not had a bilateral orchiectomy must have a plan to maintain effective GnRG-analogue therapy for the duration of the trial * Serum testosterone level \< 50 ng/dL at Screening visit * ECOG PS: 0-1 * Throughout the study, male patients and their female partners of childbearing potential must use 2 acceptable methods of birth control (1 of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration. Two acceptable methods of birth control thus include the following: * Condom (barrier method of contraception even if having sex with a pregnant woman) * One of the following is required: * Established use of oral, injected, or implanted hormonal method of contraception by the female partner * Placement of an intrauterine device (IUD) or intrauterine system (IUS) by the female partner * Additional barrier method: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository by the female partner * Tubal litigation in the female partner * Vasectomy or other procedure resulting in infertility (eg, bilateral orchiectomy) for \>6 months * Patients must have adequate organ and marrow function as defined below * Leukocytes \>3,000/mm3 * absolute neutrophil count \>1,500/mm3 * platelets \>100,000/mm3 * total bilirubin within normal institutional limits (or \<2X the upper limit of normal in those with Gilbert's disease) * AST(SGOT)/ALT(SGPT) \<1.5 X institutional upper limit of normal * creatinine within normal institutional limits OR * creatinine clearance\* \>45 mL/min/1.73 m2 for patients with creatinine levels above institutional normal * Estimated life expectancy of \> 6 months * Able to swallow the study drug as prescribed and comply with study requirements Exclusion Criteria: * Prior treatment with docetaxel-based chemotherapy * Prior treatment with abiraterone acetate * Prior treatment with cabazitaxel * Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrollment * Ongoing investigational treatment * Medical conditions such as uncontrolled hypertension, uncontrolled diabetes mellitus, cardiac disease that would, in the opinion of the investigator, make this protocol unreasonably hazardous * Major surgery within 4 weeks of enrollment * Use of an investigational therapeutic agent with 4 weeks of enrollment * History of seizure or any condition that may predispose to seizure. * History of loss of consciousness or transient ischemic attack within 12 months of enrollment * Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease) within last 3 months * Grade \> 2 treatment-related toxicity from prior therapy * History of hypersensitivity to polysorbate 80 * Any known allergy to the compounds under investigation * Any other condition which, in the opinion of the Investigator, would preclude participation in this trial