Telmisartan in Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
The goal of this clinical trial is to learn about the tolerability of telmisartan in patients with prostate cancer.

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.

Official Title
-----------------
Phase I Non-Randomized, Unblinded, Single-Center Trial of Oral Telmisartan Alone or Combined With Selected Standard of Care Therapies for Prostate Cancer

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Drug: Telmisartan
* Other: Standard of Care Regimen


Participation Criteria
=================
Eligibility Criteria
-----------------
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 who are not receiving one of the above agents 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) 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: Adults who are unable to provide informed consent. Angiotensin l receptor blocker use currently or within the 30 days prior to day 1, cycle 1. Patients unwilling or unable to have SOC PC agent(s) added to telmisartan if telmisartan is started per protocol before SOC PC treatment is administered. Inadequately treated or uncontrolled hypertension. Patients who are incarcerated, homeless, or have active substance drug/alcohol dependence or abuse history. 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Telmisartan Alone<br>Patients will receive telmisartan alone. | Drug: Telmisartan<br>* Patients will be given telmisartan alone or with standard of care chemotherapy.<br>* Other names: Micardis;|
| Experimental: Cohort 2: Telmisartan + Standard of Care Regimen<br>Patients will receive telmisartan with cabazitaxel or docetaxel without abiraterone), or telmisartan with docetaxal with abirateron or olaparib or rucaparib, or talazoparib plus enzalutamide. | Drug: Telmisartan<br>* Patients will be given telmisartan alone or with standard of care chemotherapy.<br>* Other names: Micardis;Other: Standard of Care Regimen<br>* Standard of Care Regimen<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability of oral telmisartan | 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 | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increase in tumor DNA damage | 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 | 24 months |