Enzalutamide and Mifepristone in Treating Patients With Metastatic Hormone Resistant Prostate Cancer

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PRIMARY OBJECTIVES: I. To establish the safe and pharmacologically active doses of mifepristone and enzalutamide to use in combination. (Phase I) II. To determine if mifepristone in combination with enzalutamide prolongs time to prostate-specific antigen (PSA) progression compared to enzalutamide al...

PRIMARY OBJECTIVES: I. To establish the safe and pharmacologically active doses of mifepristone and enzalutamide to use in combination. (Phase I) II. To determine if mifepristone in combination with enzalutamide prolongs time to prostate-specific antigen (PSA) progression compared to enzalutamide alone in patients with metastatic castration resistant prostate cancer. (Phase II) SECONDARY OBJECTIVES: I. To evaluate the effect of mifepristone on endocrine biomarkers such as serum cortisol and thyrotropin. II. To determine the effect of mifepristone on enzalutamide clearance and steady state enzalutamide exposure. III. To determine if mifepristone affects PSA response rate when added to enzalutamide. IV. To determine if mifepristone when added to mifepristone prolongs radiographic and clinical progression free survival according to standard working group criteria. V. To explore the role of glucocorticoid receptor (GR) and androgen receptor (AR) protein expression within circulating tumor cells as a pharmacodynamic biomarker for mifepristone and enzalutamide in castration resistant prostate cancer (CRPC). VI. To explore the expression of GR and down-stream AR/GR targets in metastatic tumor specimen prior to combination drug administration and at clinical progression. OUTLINE: This is a phase I, dose-escalation study followed by a phase II study. PHASE I: Patients receive enzalutamide orally (PO) on days 1-57 and mifepristone PO on days 29-57. Treatment continues in the absence of disease progression or unacceptable toxicity. PHASE II: Patients receive enzalutamide PO for 12 weeks per standard of care. Patients are then randomized to 1 of 2 treatment arms. ARM I: Patients receive enzalutamide PO per standard of care. ARM II: Patients receive enzalutamide PO and mifepristone PO. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 1 year.

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