Placebo-Controlled Trial of Urolithin A Supplementation in Men With Prostate Cancer Undergoing Radical Prostatectomy, URO-PRO Trial
Status
RECRUITING
Phase
PHASE2
Age
≥ 18 Years
Enrollments
90Conditions
Prostate AdenocarcinomaDrugs
Placebo AdministrationSummary
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.
Detailed 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.
Locations
2 locations Found with status Recruiting
Status
- RECRUITING
Contact Person
- Ashley E. Ross
- 312-694-1117
- [email protected]
Principal Investigator
- Stephen J Freedland
Status
- RECRUITING
Contact Person
- Judd W. Moul
- 919-668-8108
- [email protected]
Principal Investigator
- Stephen J Freedland
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 =< 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: 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
Study Plan
Arm I (urolithin A)
EXPERIMENTAL
Patients receive urolithin A PO 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.
PROCEDURE:
BiopsyDescription:
Undergo biopsyPROCEDURE:
Biospecimen CollectionDescription:
Undergo collection of blood samplesDIETARY_SUPPLEMENT:
Urolithin A SupplementDescription:
Given PO
Arm II (placebo)
PLACEBO_COMPARATOR
Patients receive placebo PO 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.
PROCEDURE:
BiopsyDescription:
Undergo biopsyPROCEDURE:
Biospecimen CollectionDescription:
Undergo collection of blood samplesDRUG:
Placebo AdministrationDescription:
Given PO
Outcome Measures
Primary Outcome Measures
Percent positive change in 8-OHdG
Secondary Outcome Measures
Changes in prostate tissue and plasma concentrations of urolithin A (Uro-A), urolithin sulfate and urolithin A glucuronide
Changes in expression of cell cycle genes
Changes in 8-OHdG expression
Timeline
Last Updated
March 7, 2025Start Date
September 5, 2023Today
May 9, 2025Completion Date ( Estimated )
May 1, 2027
Sponsors of this trial
Lead Sponsor
National Cancer Institute (NCI)
RECRUITING 
≥ 18 Years