NCT02532114

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

A Phase I Study of Niclosamide in Combination With Enzalutamide in Men With Castration-Resistant Prostate Cancer

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 5 (actual)
• Sponsor: University of Washington · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of niclosamide when given together with enzalutamide in treating patients with castration resistant prostate cancer that has spread from the primary site to other places in the body. Androgens such as testosterone can cause the growth of prostate cancer cells. Drugs like enzalutamide block androgens from driving tumor growth; however, when androgen receptor splice variants are present, these drugs may not be effective. Niclosamide may decrease the amount of androgen receptor splice variant present within tumor cells, thus promoting the anti-tumor effects of enzalutamide. Giving niclosamide together with enzalutamide may be a better treatment for prostate cancer.

Detailed description

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.

Conditions

• Castration Levels of Testosterone
• Castration-Resistant Prostate Carcinoma
• Metastatic Prostate Carcinoma
• Recurrent Prostate Carcinoma
• Stage IV Prostate Adenocarcinoma

Interventions

Type	Name	Description
DRUG	Enzalutamide	Given PO
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Niclosamide	Given PO
OTHER	Pharmacological Study	Correlative studies

Timeline

• Start date: 2015-12-31
• Primary completion: 2017-11-30
• Completion: 2017-11-30
• First posted: 2015-08-25
• Last updated: 2018-04-18

Locations

1 site across 1 country: United States