Phase Ib trial of reformulated niclosamide with abiraterone/prednisone in men with castration-resistant prostate cancer

• DOI: 10.1038/s41598-021-85969-x
• Publication Date: 2021-03-18T16:47:41Z
• Authors: Mamta Parikh; Chengfei Liu; Chun-Yi Wu; Christopher P. Evans; Marc Dall’Era; Daniel Robles; Primo N. Lara; Neeraj Agarwal; Allen C. Gao; Chong-Xian Pan
• Keywords: Niclosamide; Abiraterone acetate

Abstract Niclosamide has preclinical activity against a wide range of cancers. In prostate cancer, it inhibits androgen receptor variant 7 and synergizes with abiraterone. The approved niclosamide formulation poor oral bioavailability. primary objective this phase Ib trial was to identify maximum tolerated dose (MTD) recommended 2 (RP2D) novel reformulated orally-bioavailable niclosamide/PDMX1001 in combination abiraterone prednisone men castration-resistant cancer (CRPC). Eligible patients had progressing CRPC, adequate end-organ function, no prior treatment or ketoconazole. Patients were treated escalating doses standard prednisone. Peak trough plasma levels measured. Common Terminology Criteria for Adverse Events (CTCAE) v4.0 Prostate Cancer Working Group criteria used evaluate toxicities responses. Nine metastatic CRPC accrued, dose-limiting observed at all levels. Phase II 1200 mg orally (PO) three times daily plus 1000 PO once 5 twice daily. Trough peak concentrations exceeded the therapeutic threshold > 0.2 µM. well most frequent adverse effects diarrhea. Five out eight evaluable achieved PSA response; two undetectable radiographic response. A reformulation targeted when combined prednisone, tolerated. Further study is warranted.