Enzalutamide and Mifepristone in Treating Patients with Metastatic Castration-Resistant Prostate Cancer

Inclusion Criteria

• Histologically or cytologically confirmed prostate cancer
• Evidence of castrate testosterone level < 50 ng/dL (or surgical castration)
• Evidence of disease progression: * 2 or more new lesions on bone scan or * Progressive disease on computed tomography (CT)/magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria or * PSA progression consist of 3 PS rises, at least 2 weeks apart with the last value to be at least a 2 ng/ml
• Any prior therapy for castrate disease is acceptable except prior specific cytochrome P450 family 17 (CYP17) antagonists (e.g. abiraterone acetate, orteronel) or prior second generation AR antagonists (e.g. enzalutamide or ARN509) which are excluded; a minimum washout of 28 days for any other anticancer therapy (with the exception of sipuleucel-T, which does not need a wash out) prior to first dose of study drug is required
• Any other radiotherapy or radionuclide require 28-day washout prior to first dose of study drug
• Denosumab or zoledronic acid are allowed
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Total bilirubin =< 1.5 x the upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
• Ability to understand and the willingness to sign a written informed consent document
• Male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (one 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); AND * One of the following is required: ** Established use of oral, or 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 ligation in the female partner; ** Vasectomy or other procedure resulting in infertility (e.g., bilateral orchiectomy), for more than 6 months

Exclusion Criteria

• Therapy with other hormonal therapy, including any dose of megestrol acetate (Megace), finasteride (Proscar), dutasteride (Avodart), or any herbal product known to decrease PSA levels (e.g., saw palmetto and PC-SPES), or any systemic corticosteroid within 2 weeks prior to first dose of study drug; if the medication has a known half life such that 5 half lives is less < 2 weeks, this 5 half-life wash out is acceptable
• Inability to swallow capsules or known gastrointestinal malabsorption
• History of other malignancies, with the exception of: adequately treated non-melanoma skin cancer, adequately treated superficial bladder cancer, stage 1 or 2 solid tumor malignancies who are without evidence of disease, or other solid tumors curatively treated with no evidence of disease for >= 5 years from enrollment
• Blood pressure that is not controlled despite > 2 oral agents (systolic blood pressure [SBP] > 160 and diastolic blood pressure [DBP] > 90 documented during the screening period, with no subsequent blood pressure readings < 160/90)
• History of seizure disorder or active use of anticonvulsants
• Documented history of or current brain metastases due to seizure risk
• Corrected QT interval (QTc) on electrocardiogram (EKG) > 480 msec
• Serious intercurrent infections or non-malignant medical illnesses that are uncontrolled
• Active psychiatric illness/social situations that would limit compliance with protocol requirements
• New York Heart Association (NYHA) class II, NYHA class III, or IV congestive heart failure (any symptomatic heart failure)
• Concurrent therapy with strong inhibitors or inducers of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) or cytochrome P450 family 2, subfamily C, polypeptide 8 (CYP2C8) due to concerning possible drug-drug interactions