Polaprezinc Treatment for Enzalutamide- or Abiraterone-resistant CRPC

Study Overview
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Brief Summary
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The purpose of this study is to evaluate clinical safety and efficacy of a gastric ulcer drug, polaprezinc (POL), with the AR-inhibitor abiraterone in Chinese patients with castration-resistant prostate cancer (CRPC).

Detailed Description
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Prostate cancer (PCa) is a major disease that affects 14.1% male population worldwide with a 6.8% mortality rate in 2020 (https://gco.iarc.fr/). In China, the PCa incidence rate is lower than in Europe and the US but increases rapidly. Androgen deprivation therapy (ADT) has been the most used treatment for men with advanced prostate cancer for decades. Despite the initial favorable response, nearly all patients progress to castration-resistant prostate cancer (CRPC) and subsequently succumb to the disease within 1-3 years. Zinc-L-carnosine (ZnC), also called polaprezinc (otherwise known as PepZin GI™), is a chelated compound that contains L-carnosine and zinc. Some reports indicated that POL is effective in restoring the gastric lining, healing other parts of the gastrointestinal (GI) tract, improving taste disorders, improving GI disorders, and enhancing skin and liver. The primary mechanisms of POL action are identified as anti-inflammatory and antioxidant pathways. We have identified PRDX5 as a therapeutic target and repurposed polaprezinc (POL) as its inhibitor for the treatment of CRPC. CRPC patients will be enrolled with their fully informed consent. Patients will be on abiraterone/prednisone, abiraterone/prednisone plus polaprezinc granules, or with other treatments according to patients' wishes in consultation with physicians. Polaprezinc will be 75 mg b.i.d., for 6 months. A standard regimen will be used for other treatments. PSA will be measured every month. ECT will be taken before and after treatment.

Official Title
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Safety and Efficacy of the Stomach Ulcer Drug Polaprezinc (POL) on Enzalutamide- or Abiraterone-resistant CRPC

Conditions
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Castration-resistant Prostate Cancer

Intervention / Treatment
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* Drug: Polaprezinc group
* Drug: Control group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male patients were older than 18 years of age. Patients with measurable disease were required to have documented disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) (28) with at least one bone metastatic lesion. Patients with non-measurable disease were required to have at least two consecutive increases (relative to a reference value measured at least a week apart) in serum PSA. Patients had been taking abiraterone or enzalutamide for at least three consecutive months and showed a persistent rise in PSA. Life expectancy >6 months Exclusion Criteria: Patients had taken polaprezinc previously. Patients had cancer therapy (other than ADT) within 4 weeks before enrolment. Patients had malignancies other than prostate cancer. Patients had uncontrolled severe illness or medical conditions.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be on abiraterone/prednisone plus polaprezinc, or with other treatments according to patients'wishes in consultation with physicians.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Polaprezinc group<br>Patients will be on abiraterone plus polaprezinc (75 mg b.i.d. for 6 months) | Drug: Polaprezinc group<br>* Abiraterone plus Polaprezinc for 6 months<br>* Other names: POL;|
| Active Comparator: Control group<br>Patients will be on abiraterone, radiotherapy or chemotherapy for 6 months | Drug: Control group<br>* Abiraterone, radio- or chemotherapy<br>* Other names: OTH;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSA response | Decrease in PSA level or slowdown in PSA progression | 6 months | 
| Disease progression | Non-progressive disease (Non-PD) by ECT imaging analysis according to the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CRPC; POL