Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Patients receive urolithin A PO on study. Patients also undergo biopsy at time of surgery and collection of blood samples during screening and on study. Patients may also undergo collection of stool samples during screening and on study.

Patients receive placebo PO on study. Patients also undergo biopsy at time of surgery and collection of blood samples during screening and on study. Patients may also undergo collection of stool samples during screening and on study.

Biopsy

Undergo collection of blood and stool samples

Biospecimen Collection

Placebo Administration

Urolithin A Supplement

Stephen J. Freedland

Ashley E. Ross

Scott E. Eggener

Judd W. Moul

David F. Jarrard

Stephen J Freedland

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 serum 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) on study. Patients also undergo biopsy at time of surgery and collection of blood samples during screening and on study. Patients may also undergo collection of stool samples during screening and on study.

ARM II: Patients receive placebo orally (PO) on study. Patients also undergo biopsy at time of surgery and collection of blood samples during screening and on study. Patients may also undergo collection of stool samples during screening and on study.

Patients are followed up at 2 weeks after surgery.

Placebo-Controlled Trial of Urolithin A Supplementation in Men With Prostate Cancer Undergoing Radical Prostatectomy, URO-PRO Trial

A Phase II Placebo-Controlled Trial of Urolithin a Supplementation in Men With Prostate Cancer Undergoing Radical Prostatectomy

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

The primary endpoint will be analyzed using a linear regression model. Standard descriptive statistics, including mean, standard deviation, median and interquartile range for continuous variables, and frequency and percent for categorical variables, will be used to summarize baseline variables by treatment arm. Changes will be summarized similarly. Graphical techniques, including boxplots and histograms, will be used to examine the distribution and to assess assumptions made for the primary analysis.

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-tissue only). Will be analyzed using the same approach as the analysis of the primary endpoint. Changes in serum concentrations of Uro-A, urolithin sulfate and urolithin A glucuronide, from baseline to radical prostatectomy will be estimated and summarized using standard descriptive statistics.

The ribonucleic sequencing will be used to compute a single z-score (i.e. one data point per patient) which will represent the composite expression of 31 cell-cycle genes.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Placebo-Controlled Trial of Urolithin A Supplementation in Men With Prostate Cancer Undergoing Radical Prostatectomy, URO-PRO Trial	NCT06022822	Prostate Adenoc...	Biopsy Biospecimen Col... Placebo Adminis... Urolithin A Sup...	18 Years -	National Cancer Institute (NCI)
Placebo-Controlled Trial of Urolithin A Supplementation in Men With Prostate Cancer Undergoing Radical Prostatectomy, URO-PRO Trial	NCT06022822	Prostate Adenoc...	Biopsy Biospecimen Col... Placebo Adminis... Urolithin A Sup...	18 Years -	National Cancer Institute (NCI)

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