placebo-controlled trial of urolithin a supplementation in men with prostate cancer undergoing radical prostatectomy, uro-pro trial

Conditions: Prostate Adenocarcinoma

Summary: this phase ii randomized control trial assesses the effect of urolithin a (uro-a) supplementation compared to placebo in men with biopsy-confirmed prostate cancer undergoing radical prostatectomy (rp) progressive disease. a total of 90 men will be accrued and randomized 1:1 to receive a 1000 mg daily dose of uro-a in two 250 mg capsules po bid or two placebo capsules bid daily for 3 to 6 weeks prior to rp. the primary endpoint is to determine the effect of uro-a on decreasing prostate tumor tissue oxidative stress (measured by 8-ohdg) compared to placebo.

primary objective: i. to determine the effect of a 3-to-6-week intervention of urolithin a (uro-a) supplements versus placebo on 8-ohdg percent positive change in prostate cancer tumor tissue obtained by core needle biopsy in participants who undergo radical prostatectomy after 3 to 6 weeks of therapy. secondary objectives: i. to determine prostate tissue and plasma concentrations of uro-a, urolithin sulfate and urolithin a glucuronide, as measured by change from baseline to end-of-study, in comparison to changes from baseline to end-of-study in a control group receiving a placebo (except tissue levels, which will be compared between arms using end-of-study tissue only). ii. to compare the change in expression of cell cycle genes in prostate cancer tumor tissue from pre-study biopsy to radical prostatectomy in men receiving uro-a supplements for 3 to 6 weeks and a control group of men receiving a placebo. iii. to determine the effect of uro-a supplements on change in 8-ohdg expression in benign and tumor-adjacent prostatic tissue from pre-study biopsy to radical prostatectomy (rp) following 3-6 weeks of therapy in comparison to a control group of men receiving a placebo. exploratory objectives: i. to determine the effect of uro-a supplements on circulating levels of high sensitivity c-reactive protein (hscrp), tnf-alpha, and il-6, as measured by change from baseline to end-of-study compared with the men receiving a placebo. ii. to compare change in tumor gene expression patterns of hallmark androgen signaling between study arms. iii. to determine the effect of a 3-to-6-week intervention of urolithin a (uro-a) supplements versus placebo on 8-ohdg h-index (percent staining positive at each score in a 0-3 scale) change in prostate cancer tumor tissue obtained by core needle biopsy at baseline and at radical prostatectomy after 3 to 6 weeks of therapy. iv. to collect stool samples for future analyses to determine the effect of uro-a supplements on change in stool microbiome 16s ribosomal ribonucleic acid (rrna) gene sequencing. outline: patients are randomized to 1 of 2 arms. arm i: patients receive urolithin a orally (po) twice daily (bid) for 3-6 weeks prior to standard of care (soc) rp. patients also undergo biopsy at time of surgery and collection of blood samples during screening and on study. arm ii: patients receive placebo orally (po) twice daily (bid) for 3-6 weeks prior to soc rp. patients also undergo biopsy at time of surgery and collection of blood samples during screening and on study. patients are followed up at 2 weeks after surgery.

Eligibility criteria:
inclusion criteria: * participants must have pathologically confirmed adenocarcinoma of the prostate with formalin-fixed paraffin embedded (ffpe) biopsy tissue available for analysis. diagnosis can be any time in the six months prior to registration/randomization * participants \>= 18 years will be enrolled. because no dosing or adverse event (ae) data are currently available on the use of urolithin a in participants \< 18 years of age, children and adolescents are excluded from this study * eastern cooperative oncology group (ecog) performance status =\ = 60%) * absolute neutrophil count \>= 1,000/microliter * platelets \>= 100,000/microliter * total bilirubin =\< 1.5 x institutional upper limit of normal (uln) note: higher total bilirubin levels (=\< 3 mg/dl) can be allowed if due to known benign liver condition, i.e. gilbert's * aspartate aminotransferase (ast) (serum glutamic-oxaloacetic transaminase \[sgot\])/alanine aminotransferase (alt) (serum glutamate pyruvate transaminase \[sgpt\]) =\< 3.0 x institutional upper limit of normal * creatinine =\< 1.5 x institutional upper limit of normal * human immunodeficiency virus (hiv)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial * for participants with evidence of chronic hepatitis b virus (hbv) infection, the hbv viral load must be undetectable on suppressive therapy, if indicated * participants with a history of hepatitis c virus (hcv) infection must have been treated and cured. for patients with hcv infection who are currently on treatment, they are eligible if they have an undetectable hcv viral load * participants on chronic suppressive antiviral therapy for herpes simplex virus (hsv) are eligible * scheduled to undergo rp in the next 3-6 weeks * ability to understand and the willingness to sign a written informed consent document exclusion criteria: * participants with prior primary treatment or hormonal therapy for prostate cancer (pc) * participants with documented active alcohol and illegal substance dependency * participants already receiving urolithin a (mitopure, commercially available in the united states), or pomegranate supplements. note: other supplements are allowed but must be documented * participants receiving any other investigational agents * history of allergic reactions attributed to compounds of similar chemical or biologic composition to urolithin a * uncontrolled intercurrent illness, or psychiatric illness/social situations that would limit compliance with study requirements