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

PRIMARY OBJECTIVES: I. To determine the safety of niclosamide (PDMX1001/niclosamide) and enzalutamide in patients with castration-resistant prostate cancer (CRPC). II. To determine the recommended phase II dose (RP2D) of PDMX1001/niclosamide and enzalutamide for the treatment of patients with CRPC. SECONDARY OBJECTIVES: I. To determine the pharmacokinetics of PDMX1001/niclosamide. II. To determine the number of patients who have a prostate-specific antigen (PSA) response that is a 50% or more reduction from the baseline. III. To identify overall responses as determined by the Prostate Cancer Working Group 2 (PCWG2) criteria. IV. To evaluate the progression-free survival (PFS) of CRPC patients treated with PDMX1001/niclosamide and enzalutamide. V. To evaluate molecular correlatives for patient response and outcomes through the analysis of patient baseline tumor specimens (diagnostic biopsy) along with serial blood specimens. OUTLINE: This is a dose-escalation study of niclosamide. Patients receive niclosamide orally (PO) twice daily (BID) and enzalutamide PO once daily (QD) on weeks 1-4. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 3 months.