Folate Study in Men With Advanced Prostate Cancer

A Phase II, Open Label, Randomized Controlled Pilot Study Evaluating Trimethoprim in Patients Commencing Androgen Deprivation Therapy for Prostate Cancer

The researchers hope to learn if Trimethoprim, 150mg taken daily for 3 months, is a safe and effective way to reduce folate levels at time of Androgen Deprivation Therapy (ADT) in men with advanced prostate cancer.

This study will help find out what effects, good and/or bad, this drug has on people who take it and on its effect on the disease. The safety of this drug in humans has been tested in prior research studies; however, some side effects may not yet be known.

Study Overview

• Status: Not yet recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Trimethoprim Tablets

Detailed Description

While taking part in this study, participants will be asked to attend approximately 4 to 7 visits - depending on what randomized arm they are in - with the researchers or study staff.

It may be necessary for participants to return to the hospital/clinic every 1-3 months as part of their regular care. Research procedures will be completed at the same time as these routine standard of care visits. Participants will be asked to stop taking any supplements or medications containing folic acid or potassium prior to enrolling in the study.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Alexandrea Cronin; Phone Number: (858) 822-5354; Email: cancerCTO@health.ucsd.edu
• Study Contact Backup: Name: Michael A Liss, MD, PhD; Phone Number: (858) 822-5354; Email: cancerCTO@health.ucsd.edu

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • University of California, San Diego
      • Contact: Alexandrea Cronin; Phone Number: (858) 822-5354; Email: cancerCTO@health.ucsd.edu
      • Contact: Michael A Liss, MD, PhD; Phone Number: (858) 822-5354; Email: cancerCTO@health.ucsd.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

INCLUSION CRITERIA

1. Provision of signed and dated informed consent form.
2. Stated willingness to comply with all study procedures and availability for the duration of the study.
3. Age ≥ 18 years.
4. Proven diagnosis of prostate cancer (intermediate unfavorable risk, high risk, very high risk localized per the 2025 NCCN guidelines), or metastatic hormone-sensitive prostate cancer with confirmation by pathology report and most recent prostate biopsy procedure note.
5. Prostate cancer treatment naïve.
6. Commencing androgen deprivation therapy for prostate cancer within 4 weeks of enrollment in the study. Note that radiotherapy and androgen receptor pathway inhibitors, apart from abiraterone, are allowed in both arms.
7. Hemoglobin ≥ 11 g/dL.
8. Red blood cell folate > 750 nmol/L.
9. Homocysteine < 15 micromol/L.
10. Creatine clearance within the normal range.
11. Eastern Cooperative Oncology Group performance status 0-1
12. Stated willingness to abstain from consumption of any supplements or medications containing folic acid or potassium.
13. Ability to take oral medications and be willing to adhere to trimethoprim and androgen deprivation therapy regimens.
14. For participants able to cause a pregnancy: use of condoms or other methods to ensure effective contraception with partner.
15. Agreement to adhere to lifestyle considerations described in the protocol throughout study duration.

EXCLUSION CRITERIA

1. Current use of memantine, phenytoin, and any medications that may significantly interact with TMP, including prohibited concomitant medications listed in the protocol.
2. Current use of medications that would interfere with folate metabolism (for example, methotrexate).
3. Treatment with another investigational drug while on this study.
4. Treatment with hormone therapy, immunotherapy, chemotherapy and/or radiation therapy for any malignancies within the past 2 years. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
5. History of renal or hepatic disease, including history of hepatitis B and C.
6. Recurrent urinary tract infections, urinary retention, or neurological conditions affecting bladder function.
7. Known hypersensitivity or allergy to trimethoprim.
8. Hematological disorders (including megaloblastic anemia).
9. Commencing chemotherapy for metastatic prostate cancer.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trimethoprim plus androgen deprivation therapy; Administration of trimethoprim to reduce folic acid levels at the time of standard of care androgen deprivation therapy.	Drug: Trimethoprim Tablets; Trimethoprim 150mg is administered once daily for 3 months
No Intervention: Standard of Care treatment; Standard of care treatment participants will have no intervention, only their prescribed androgen deprivation therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Trimethoprim	Proportion of participants with adverse events and serious adverse events as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).	From first dose of study therapy through 1 month after completion of study therapy.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Folate Levels	Comparing the TMP + SOC arm to the SOC alone arm will allow us to determine effect of TMP on measures of folic acid	Baseline, 1, 2, 3 and 6 months
Levels of Red Blood Cells (RBC) Folate	Comparing the TMP + SOC arm to the SOC alone arm will allow us to determine effect of TMP on measures of folic acid	Baseline, 1, 2, 3 and 6 months
Prostate Specific antigen (PSA) levels in blood	Prostate specific antigen (PSA) is an extensively studied biomarker with prognostic implications after initiation of ADT. In patients with prostate cancer, higher PSA after initiation of ADT is associated with shorter progression free survival	Baseline, 1, 2, 3 and 6 months
Urine exsomal PSMA	A further emerging biomarker of prostate cancer is urine-derived exosome PSMA60. PSMA has been shown to be elevated in hormone resistant forms of metastatic prostate cancer60. The role of urine-derived exosome PSMA in metastatic disease and its relationship to folic acid and androgen deprivation is evolving and will be examined in this study.	1 month, 3 months and 6 months
Testosterone levels	Testosterone level is measured to determine progression free survival as part of standard of care	12, 18 and 24 months
Microbiome/metabolomic analysis	Measure changes in gut microbiome after administration of TMP in men on ADT. Analysis of the gut microbiome in this context as a secondary aim will provide much needed data to help further understand the relationship of the gut microbiome in folic acid synthesis.	1 month, 3 months and 6 months

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Investigators: Principal Investigator: Michael A Liss, MD, PhD, University of California, San Diego

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: July 30, 2024
• First Submitted That Met QC Criteria: July 30, 2024
• First Posted (Actual): August 2, 2024

Study Record Updates

• Last Update Posted (Actual): November 12, 2025
• Last Update Submitted That Met QC Criteria: November 9, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Folic Acid; Androgen deprivation therapy
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Trimethoprim
• Other Study ID Numbers: 812072

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Any manuscript, abstract or other publication or presentation of results or information arising in connection with the trial (including an ancillary trial involving trial subjects) will be prepared in conjuction with the study Data Safety Monitoring Board, and the statistician.
• IPD Sharing Time Frame: At the time of publication in a peer review journal or presentation at a medical conference.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No