Clinical trial NCT06536374: Folate Study in Men With Advanced Prostate Cancer
Official title: A Phase II, Open Label, Randomized Controlled Pilot Study Evaluating Trimethoprim in Patients Commencing Androgen Deprivation Therapy for Prostate Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: Androgen deprivation therapy
Folic Acid
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
First posted: 2024-08-02
Enrollment: 50
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is a Phase II, open label, randomized controlled trial. Subjects will be randomized 1:1 to either Trimethoprim (TMP) + (Standard of Care) SOC or SOC alone
Primary purpose: TREATMENT

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

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Safety of Trimethoprim Therapy
timeFrame: Baseline (start of treatment TMP+SOC or SOC) to 6 months
measure: Adherence to Trimethoprim Treatment
timeFrame: 3 months
Secondary outcomes:
measure: Serum Folate Levels
timeFrame: Baseline, 1, 2, 3 and 6 months
measure: Levels of Red Blood Cells (RBC) Folate
timeFrame: Baseline, 1, 2, 3 and 6 months
measure: Prostate Specific antigen (PSA) levels in blood
timeFrame: Baseline, 1, 2, 3 and 6 months
measure: Urine exsomal PSMA
timeFrame: 1 month, 3 months and 6 months
measure: Testosterone levels
timeFrame: 12, 18 and 24 months
measure: Microbiome/metabolomic analysis
timeFrame: 1 month, 3 months and 6 months
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: The University of Texas Health Science Center at San Antonio
state: Texas
city: San Antonio
country: United States
facility: University Health System
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center at San Antonio
name: Michael A Liss, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: