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

Inclusion Criteria: * Have signed an informed consent document indicating that the subject understands the purpose of and procedures required for the study and are willing to participate in the study * Be willing/able to adhere to the prohibitions and restrictions specified in this protocol * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 * Documented histologically confirmed adenocarcinoma of the prostate * Patient must have evidence of castration resistant prostate cancer as evidenced by a confirmed rising PSA (per Prostate Cancer Working Group 2 \[PCWG2\] criteria) and a castrate serum testosterone level (i.e. =\< 50 mg/dL) * Patient must be eligible for treatment with enzalutamide * Patient must have previously progressed on abiraterone (either by PCWG2 criteria or Response Evaluation Criteria in Solid Tumors \[RECIST\] criteria) * Documented metastatic disease on bone scan, computed tomography (CT) scan or magnetic resonance imaging (MRI) Exclusion Criteria: * Have known allergies, hypersensitivity, or intolerance to enzalutamide or niclosamide or their excipients * Ongoing systemic therapy (other than a gonadotropin releasing hormone \[GnRH\] agonist/antagonist) for prostate cancer including, but not limited to: * Cytochrome P450, family 17 (CYP-17) inhibitors (e.g. ketoconazole, abiraterone) * Antiandrogens (e.g. bicalutamide, nilutamide) * Second generation antiandrogens (e.g. ARN-509) * Note: patients receiving ongoing treatment with enzalutamide will be allowed to join the study * Immunotherapy (e.g. sipuleucel-T, ipilimumab) * Chemotherapy (e.g. docetaxel, cabazitaxel) * Radiopharmaceutical therapy (e.g. radium-223, strontium-89, samarium-153) * Have any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements * Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule * Severe hepatic impairment (Child-Pugh class C) * Severe renal impairment (creatinine clearance =\< 30 ml/min) * History of prior seizures * Central nervous system metastases * Symptomatic patients who, in the opinion of the investigator, may benefit from docetaxel-based chemotherapy