Folate Study in Men With Advanced Prostate Cancer
- Registration Number
- NCT06536374
- Brief Summary
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.
- Detailed Description
While taking part in this study, participants will be asked to attend approximately 5-7 visits 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. Subjects randomized to the treatment arm may be asked to attend 2 additional research only visits.
Participants will be asked to stop taking any supplements or medications containing folic acid or potassium prior to enrolling in the study
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- Male
- Target Recruitment
- 50
- Have proven diagnosis of prostate cancer with confirmation by pathology report and most recent prostate biopsy procedure note.
- Commencing Androgen Deprivation Therapy (ADT) (example. intermediate/high risk localized prostate cancer starting ADT+ radiotherapy, metastatic hormone-sensitive prostate cancer (mHSPC) treated with or without androgen receptor pathway inhibitor (ARPI)- see section 4.4) as soon as able (within 2 weeks)
- Normal Complete blood count (CBC), (Red Blood Cell) RBC folate >750nmol/L and homocysteine <15mcmol/L and normal creatine clearance (obtained within 30 days prior to registration)
- Be age 18 or older.
- Able to stop current supplements that include folic acid.
- Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Patient must be willing to abstain from consumption of any supplements or medications containing folic acid or potassium.
- Patient must have the ability to understand and the willingness to provide written informed consent.
- Patients with metastatic prostate cancer commencing chemotherapy.
- Patients with known hematological disorders (including megaloblastic anemia)
- Patients with known hypersensitivity or allergy to trimethoprim
- Patients with recurrent urinary tract infections, urinary retention or neurological conditions affecting bladder function.
- Unable to give informed consent.
- Age < 18.
- Unable to swallow pills.
- Prisoners.
- Patient must not have a history of renal or hepatic disease, including history of hepatitis B and C
- Patient must not have undergone treatment of hormone therapy, immunotherapy, chemotherapy and/or radiation 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.
- Patient must not be taking any medications that may significantly interact with trimethoprim including prohibited concomitant medications.
- Patient must not receive any other investigational agents while on this study.
- Patients taking other medications that would interfere with folate metabolism (ex. methotrexate)
- Patients taking memantine.
- Patients taking phenytoin.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Folate receptor blocker with Standard of Care Trimethoprim Tablets Administration of a dietary intervention to reduce folic acid at the time of standard of care androgen deprivation therapy.
- Primary Outcome Measures
Name Time Method Adherence to Trimethoprim Treatment 3 months Adherence is based on pill counts and drug diary logs
Safety of Trimethoprim Therapy Baseline (start of treatment TMP+SOC or SOC) to 6 months The primary outcome is safety using the Common Terminology Criteria for Adverse Events (CTCAE) v5. Comparing the TMP + SOC arm to the SOC alone arm will allow us to confirm if any safety issues are related to the TMP alone. Summary results will be reported as numbers of participants experiencing adverse events classified as Grade 3 and above.
- Secondary Outcome Measures
Name Time Method Levels of Red Blood Cells (RBC) Folate Baseline, 1, 2, 3 and 6 months Comparing the TMP + SOC arm to the SOC alone arm will allow us to determine effect of TMP on measures of folic acid
Urine exsomal PSMA 1 month, 3 months and 6 months 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.
Testosterone levels 12, 18 and 24 months Testosterone level is measured to determine progression free survival as part of standard of care
Serum Folate Levels Baseline, 1, 2, 3 and 6 months Comparing the TMP + SOC arm to the SOC alone arm will allow us to determine effect of TMP on measures of folic acid
Prostate Specific antigen (PSA) levels in blood Baseline, 1, 2, 3 and 6 months 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
Microbiome/metabolomic analysis 1 month, 3 months and 6 months 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.
Trial Locations
- Locations (2)
The University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
University Health System
🇺🇸San Antonio, Texas, United States