A Phase Ib clinical trial with niclosamide plus abiraterone for Castration Resistant Prostate Cancer (CRPC)

DESCRIPTION provided by applicant We will conduct a Phase Ib clinical trial to determine the recommended Phase II dose RP D and examine the toxicity of the niclosamide and abiraterone combination in the treatment of Castration Resistant Prostate Cancer CRPC and conduct pilot molecular correlative studies Our goal is to develop a novel treatment strategy for advanced prostate cancer by targeting both full length androgen receptor signaling as well as its variants Abiraterone is commonly used in treating CRPC However the response is usually short and resistance to abiraterone is the most common cause of treatment failure Considerable evidence from both clinical and experimental studies demonstrated that androgen receptor variant AR V plays vital roles in induction of resistance to abiraterone therapy AR V is not targeted by abiraterone Therefore there is urgent need to develop novel agents that target AR V to overcome resistance We discovered niclosamide as a novel inhibitor of AR V and obtained extensive preclinical data showing that niclosamide synergizes abiraterone in treating CRPC For this SBIR Phase I we proposed to formulate niclosamide capsule under GMP procedures with the full CMC chemistry manufacturing and controls information and recruit patients to conduct a single center single arm open labeled trial at University of California Davis We will conduct pilot molecular correlated studies in these patients Successful completion of the proposed studies will lay foundation for future phase II clinical trials and lead to an SBIR Phase II application This project if successful is high yielding and can possibly benefit hundreds of thousands of prostate cancer patients every year PUBLIC HEALTH RELEVANCE Considerable evidence from both clinical and experimental studies demonstrated that androgen receptor variant AR V plays vital roles in induction of resistance to abiraterone therapy This SBIR Phase I project is conduct a Phase Ib clinical trial to determine the recommended Phase II dose RP D and examine the toxicity of the niclosamide AR V inhibitor and abiraterone combination in the treatment of Castration Resistant Prostate Cancer CRPC and conduct pilot molecular correlative studies