Prostate Cancer
Conditions
Brief summary
The goal of this clinical trial is to learn about the tolerability of telmisartan in patients with prostate cancer, but evidence for treatment efficacy will also be gathered.
Detailed description
The primary objective of this study is to test the tolerability of oral telmisartan given as a single agent or combined with specific standard of care agents in selected participants with PC. Patients will be defined as tolerating telmisartan if they maintain systolic blood pressure \>110 mm Hg and are without greater than grade 2 toxicities as defined in the Common Terminology Criteria for Adverse Events v5.1 for at least 60 days total telmisartan treatment.
Interventions
DRUGTelmisartan
Patients will be given telmisartan alone or with standard of care chemotherapy.
OTHERStandard of Care Regimen
Standard of Care Regimen
Sponsors
Tyler J Curiel
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must be ≥18 years of age. * Participants must be able and willing to provide informed consent or have a surrogate capable of providing same. * Participants must not require immediate change in SOC treatment, i.e., patients with stable PSA (do not meet PCWG310 criteria for PSA progression), or with rising PSA but they remain on SOC treatment (defined as having met PCWG3 criteria for PSA progression, but do not have clinical/radiographic progression and have not met criteria for an immediate change in therapy based on PSA doubling time) as determined by their primary oncologist * Participants must be receiving or likely to receive one of the following SOC agents for PC: cabazitaxel, docetaxel (alone or plus abiraterone) olaparib, rucaparib, or talazoparib plus enzalutamide * Participants must have * ECOG performance status of 0-2 * Adequate hepatic (SCOT ≤3x ULN) and renal function (serum creatinine ≤2.5 or estimated GFR \>30 cc/min) * Standing systolic blood pressure \>/= 110mm Hg * If not on active surveillance, patient mut have castrate level testosterone * No contraindication to telmisartan, including ACE inhibitor use in the 6 weeks prior to projected telmisartan start on trial * All participants must have a systolic blood pressure \>110 mm Hg during study enrollment assessment and throughout the study * If participants are concurrently treated for hypertension, they must be able to allow telmisartan in addition to, or replacing their antihypertensive regimen * Participants must be able to withstand planned research phlebotomies (Hb \>10 gm/dl). * Participants must have a blood prostate specific antigen \> 1 ng/ml at study entry using the Roche Cobas immunoassay. * Participants must be able to take or have taken their own blood pressure per the study protocol (daily during telmisartan escalation and for two weeks after the final escalation and weekly thereafter for the following month and then monthly) if normotensive at enrollment.
Exclusion criteria
Participants who fall into one of the following categories will NOT be eligible for this study: * Angiotensin l receptor blocker use currently or within the 30 days prior to day 1, cycle 1. * Patients with hypertensive urgency or emergency as defined in N Engl J Med. 2019 Nov 7;381(19):1843-1852. doi:10.1056/NEJMep1901117 * Patients who are incarcerated or homeless * Patients who are receiving PC-specific treatment aside from cabazitaxel, docetaxel, olaparib, rucaparib, abiraterone or talazoparib plus enzalutamide or have plans to undergo the same during the study period, except local irradiation therapy to PC lesions. * Patients on lithium therapy in any form * Patients who received rituximab or amifostine within 30 days prior to first telmisartan dose on this study * Patients on ramapril * Patients on digoxin who do not consent to monthly digoxin blood level testing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability of oral telmisartan | 12 months | Ability of the participant to tolerate telmisartan alone or with standard of care agents as defined by maintaining a systolic blood pressure \>110mmHG and are without greater than grade 2 toxicities |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Increase in tumor DNA damage | 24 months | Determine if telmisartan increases tumor DNA damage or alters immunity in ways consistent with anti-tumor activity when given alone or with selected standard of care treatments in selected patients with prostate cancer as determined by counting gamma-H2AX foci in tissue sections and peripheral blood mononuclear cells |
Countries
United States
Contacts
CONTACTKayla Fay
PRINCIPAL_INVESTIGATORRodwell Mabaera, MD
Dartmouth Health
Outcome results
None listed