Niclosamide and Enzalutamide in Treating Patients With Castration-Resistant, Metastatic Prostate Cancer

PRIMARY OBJECTIVES: I. Determine the safety and tolerability of three-times-daily (TID) oral niclosamide combined with enzalutamide in men with castration-resistant prostate cancer (CRPC) that has progressed on abiraterone (abiraterone acetate). SECONDARY OBJECTIVES: I. Determine the effect of niclosamide plus enzalutamide on androgen receptor splice variant (AR-V) expression as determined by quantitative reverse-transcriptase-polymerase-chain-reaction (qRT-PCR). II. Determine the pharmacokinetic profile of three-times-daily (TID) oral niclosamide in men with castration-resistant prostate cancer (CRPC) that has progressed on abiraterone. III. Determine the prostate specific antigen (PSA) response rate (i.e. proportion of subjects with \>= 50% decline in PSA from pre-study baseline) after 28-days of niclosamide plus enzalutamide. IV. Determine the effect of niclosamide plus enzalutamide on protein expression and the transcriptional program of circulating tumor cells. OUTLINE: This is a dose-escalation study of niclosamide. Patients receive niclosamide orally (PO) TID and enzalutamide PO daily. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at days 58 and 88.