CAPSAICIN Trial: Assessing Capsaicin as a Chemopreventive Agent for Prostate Cancer

Rationale A large body of evidence supports the role of dietary factors in prostate cancer development and progression. Most of this evidence suggests that diet high in fat including red meat and low in micronutrients and other anti-oxidants, increases the risk of disease. We are interested in the therapeutic potential of the dietary agent, capsaicin (CAP). Capsaicin is the active compound in chili peppers, and related plants. Pre-clinical studies have found that capsaicin has potent growth inhibitory and pro-apoptotic effects. It is thought that consumption of a capsaicin supplement may have a clinical benefit for subjects with localized prostate cancer who have chosen to be managed by active surveillance or improve surgical outcome of patients undergoing radical prostatectomy. Objective(s) Primary • To assess the effect of capsaicin daily therapy on the expression of ki67 and p27 biomarkers in a post-treatment biopsy or prostate specimen from RP. Secondary * To assess the effect of therapy with repeat oral dosing of capsaicin two times daily on Prostate Specific Antigen (PSA) kinetics in men on active surveillance for localized prostate cancer * To assess the effect of therapy with repeat oral dosing of capsaicin two times daily on grade and the presence of prostatic intraepithelial neoplasia (PIN) in a post-treatment biopsy * To assess the effect of therapy with repeat oral dosing of capsaicin two times daily on the expression of markers of apoptosis, cell cycle, TRP-V1 and TRP-V6 * To assess the safety and tolerability of capsaicin therapy in men on active surveillance (AS) for prostate cancer * To assess alterations in prostate volume and time to recurrence Endpoint(s) Primary • Determine effect of capsaicin therapy on expression of ki67 and p27 biomarkers in a post-treatment biopsy Secondary * Determine effect of capsaicin daily therapy on PSA kinetics in men on active surveillance for localized prostate cancer * To evaluate the effect of capsaicin daily therapy on grade and the presence of prostatic intraepithelial neoplasia (PIN) in post treatment biopsy * To assess the effect of capsaicin therapy on the expression of markers of apoptosis, cell cycle, TRP-V1 and TRP-V6 Safety and Tolerability * Adverse events (AEs) * Clinical laboratory evaluations (PSA, electrolytes, biochemistry, hematology, cholesterol) Pharmacodynamic * Levels of serum capsaicin (CAP) * Levels of serum testosterone (T) Study Design This is a phase II, open label, single centre study to evaluate the efficacy and safety of repeat oral dosing of one CAP capsules twice times daily for 6 months prior to a prostate biopsy in men on active surveillance for localized prostate cancer, as well as 6 weeks prior to radical prostatectomy (RP). Study Population One hundred men men monitored (sixty from active surveillance (AS) and forty patients scheduled to undergo radical prostatectomy) will be eligible for participation. Subjects must satisfy all inclusion and exclusion criteria. A sufficient number will be enrolled to achieve at least 100 completed subjects