Docetaxel/Prednisone Versus Docetaxel/Prednisone and Enzalutamide in Castration-Resistant Prostate Cancer (Doce/Enza)

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