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

Last updated: May 2, 2025
Sponsor: National Cancer Institute (NCI)
Overall Status: Active - Recruiting

Phase

2

Condition

Adenocarcinoma

Prostate Cancer

Treatment

Urolithin A Supplement

Biopsy

Placebo Administration

Clinical Study ID

NCT06022822
NCI-2023-03835
NWU22-12-01
UG1CA242643
NCI-2023-03835
P30CA060553
NCI22-12-01
UG1CA189828
  • Ages > 18
  • Male

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Participants must have pathologically confirmed adenocarcinoma of the prostate withformalin-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 ofage, children and adolescents are excluded from this study

  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

  • Absolute neutrophil count >= 1,000/microliter

  • Platelets >= 100,000/microliter

  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) Note: Highertotal bilirubin levels (=< 3 mg/dL) can be allowed if due to known benign livercondition, 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 effectiveanti-retroviral therapy with undetectable viral load within 6 months are eligiblefor this trial

  • For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBVviral load must be undetectable on suppressive therapy, if indicated

  • Participants with a history of hepatitis C virus (HCV) infection must have beentreated 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 consentdocument

Exclusion

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 theUnited States), or pomegranate supplements. Note: Other supplements are allowed butmust be documented

  • Participants receiving any other investigational agents

  • History of allergic reactions attributed to compounds of similar chemical orbiologic composition to urolithin A

  • Uncontrolled intercurrent illness, or psychiatric illness/social situations thatwould limit compliance with study requirements

Study Design

Total Participants: 90
Treatment Group(s): 5
Primary Treatment: Urolithin A Supplement
Phase: 2
Study Start date:
September 12, 2024
Estimated Completion Date:
May 01, 2027

Study Description

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.

Connect with a study center

  • Cedars Sinai Medical Center

    Los Angeles, California 90048
    United States

    Active - Recruiting

  • Northwestern University

    Chicago, Illinois 60611
    United States

    Active - Recruiting

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois 60637
    United States

    Site Not Available

  • Duke University Medical Center

    Durham, North Carolina 27710
    United States

    Active - Recruiting

  • University of Wisconsin Carbone Cancer Center

    Madison, Wisconsin 53792
    United States

    Site Not Available

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin 53792
    United States

    Site Not Available

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