Telmisartan for Prostate Cancer

Overseen By Kayla Fay

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Tyler J Curiel

Must be taking: Cabazitaxel, Docetaxel, Olaparib, others

Must not be taking: Angiotensin blockers, Lithium, Ramapril, others

Disqualifiers: Hypertensive urgency, Incarcerated, Homeless, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 60 days

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if telmisartan, a medication, is tolerable and potentially effective for treating prostate cancer. Participants will take telmisartan either alone or with other standard cancer treatments. Men with stable prostate cancer markers, such as PSA (a protein that helps track cancer progression), and who are currently on or likely to receive specific cancer drugs, might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Specifically, you cannot use angiotensin receptor blockers or ACE inhibitors within 30 days before starting the trial. If you are on digoxin, you must agree to monthly blood level testing.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that telmisartan, a drug commonly used for high blood pressure, does not increase cancer risk more than other similar medications. One study found cancer rates were nearly the same for those taking telmisartan and those on other similar drugs: 16.3 cases versus 15.0 cases per 1,000 person-years. This suggests telmisartan is generally safe regarding cancer risk.

This trial is currently in its early stages. Researchers are primarily assessing the treatment's safety for participants. Telmisartan has been safely used for other health issues, which is reassuring. However, this trial will provide more specific information about its safety for prostate cancer patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Telmisartan is unique in prostate cancer treatment because it is traditionally used for managing high blood pressure. Researchers are excited about its potential new role due to its ability to block the angiotensin II receptor, which may help slow cancer growth. Unlike standard treatments like chemotherapy that directly attack cancer cells, telmisartan offers a different approach by potentially disrupting the environment that supports cancer cell survival. Additionally, combining telmisartan with existing therapies like cabazitaxel or docetaxel could enhance treatment effectiveness, offering a fresh strategy against prostate cancer.

What evidence suggests that telmisartan might be an effective treatment for prostate cancer?

Research suggests that telmisartan, a drug commonly used to treat high blood pressure, might also aid in treating prostate cancer. In this trial, participants will join different treatment arms. Some will receive telmisartan alone, while others will receive it combined with a standard care regimen. Studies have found that telmisartan can slow the growth of prostate cancer cells and even cause cell death, depending on the dose. For instance, it reduced the survival of certain prostate cancer cells and halted their growth. While these results are promising, they primarily come from lab studies, so more research is needed to understand its effectiveness in people with prostate cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Rodwell Mabaera, MD

Principal Investigator

Dartmouth Health

Are You a Good Fit for This Trial?

Men over 18 with prostate cancer and a PSA level >1 ng/ml can join this trial. They must be stable on or likely to start standard treatments, able to monitor their blood pressure, consent themselves (or have someone who can), not need immediate treatment changes, and have normal or controlled high blood pressure that allows for telmisartan use.

Inclusion Criteria

I can give my consent or have someone who can consent for me.

I can safely undergo blood draws for the study.

All participants must have a systolic blood pressure >110 mm Hg during study enrollment assessment and throughout the study.

Exclusion Criteria

My high blood pressure is not well-controlled.

I haven't taken rituximab or amifostine in the last 30 days.

I am not on any prostate cancer-specific treatments except for local radiation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive telmisartan alone or in combination with standard of care therapies for prostate cancer

60 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Long-term follow-up

Participants are monitored for secondary outcomes such as tumor DNA damage and prostate specific antigen levels

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Telmisartan

Trial Overview This study is testing the safety of adding telmisartan to the usual prostate cancer treatments. Participants will either receive telmisartan alongside their standard care regimen or continue with just the standard care to see how well they tolerate the addition of telmisartan.

How Is the Trial Designed?

Group I: Cohort 2: Telmisartan + Standard of Care Regimen Experimental Treatment 2 Interventions

Patients will receive telmisartan with cabazitaxel or docetaxel without abiraterone), or telmisartan with docetaxal with abirateron or olaparib or rucaparib, or talazoparib plus enzalutamide.

Group II: Cohort 1: Telmisartan Alone Experimental Treatment 1 Intervention

Patients will receive telmisartan alone.

Telmisartan is already approved in United States, European Union for the following indications:

Approved in United States as Micardis for:

• High Blood Pressure
• Prevention of Cardiovascular Disease
• Cardiovascular Risk Reduction

Approved in European Union as Micardis for:

• Hypertension
• Reduction of cardiovascular morbidity in patients with manifest atherothrombotic cardiovascular disease

Who Is Running the Clinical Trial?

Tyler J Curiel

Lead Sponsor

Trials

2

Recruited

70+

Published Research Related to This Trial

Abiraterone acetate (AA) combined with prednisone significantly improves overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC), regardless of the presence of visceral disease, with a median OS increase of 4.6 months for those with visceral disease.

The treatment also shows comparable improvements in secondary outcomes, such as radiographic progression-free survival and PSA response rates, indicating that visceral disease does not limit the effectiveness of abiraterone in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploratory analysis of the visceral disease subgroup in a phase III study of abiraterone acetate in metastatic castration-resistant prostate cancer. Goodman, OB., Flaig, TW., Molina, A., et al.[2022]

Chemotherapy with mitoxantrone and prednisone can provide palliative benefits for patients with symptomatic hormone-refractory prostate cancer and is generally well tolerated, even in elderly patients, although its use is limited by potential cardiotoxicity.

Docetaxel and paclitaxel may offer higher rates of prostate-specific antigen response compared to mitoxantrone, but they come with increased toxicity, and large phase III trials are underway to compare their effectiveness directly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a role for chemotherapy in prostate cancer? Canil, CM., Tannock, IF.[2022]

Telmisartan, an angiotensin II receptor blocker (ARB), significantly inhibits the growth of prostate cancer (PC) cells in a concentration- and time-dependent manner, while not affecting normal prostate stromal cells, indicating its potential as a targeted treatment.

The study suggests that Telmisartan's antiproliferative effects on PC cells may be mediated through the activation of peroxisome proliferator-activated receptor (PPAR)-gamma, highlighting its mechanism of action in promoting early apoptosis and DNA fragmentation in cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Telmisartan is a potent target for prevention and treatment in human prostate cancer. Funao, K., Matsuyama, M., Kawahito, Y., et al.[2018]

Telmisartan, an angiotensin II receptor blocker (ARB), significantly inhibits the growth of various urological cancer cell lines, including renal cell carcinoma, bladder cancer, prostate cancer, and testicular cancer, in a dose- and time-dependent manner.

Unlike other ARBs, telmisartan induces early apoptosis and DNA fragmentation in cancer cells, suggesting it may act through PPAR-γ activation, making it a promising candidate for the prevention and treatment of urological cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Telmisartan inhibits human urological cancer cell growth through early apoptosis. Matsuyama, M., Funao, K., Kuratsukuri, K., et al.[2021]

In a study of 770 men with metastatic, hormone-independent prostate cancer, treatment with docetaxel and estramustine resulted in a median overall survival of 17.5 months, compared to 15.6 months for those receiving mitoxantrone and prednisone, indicating a significant survival benefit.

Docetaxel and estramustine also led to a longer median time to disease progression (6.3 months) and a higher rate of PSA declines of at least 50% (50% vs. 27%), although it was associated with more severe side effects like neutropenic fevers and nausea compared to mitoxantrone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. Petrylak, DP., Tangen, CM., Hussain, MH., et al.[2022]

Telmisartan, an angiotensin II receptor blocker (ARB), effectively inhibits the proliferation of prostate cancer cells and reduces prostate-specific antigen (PSA) expression, suggesting its potential as a treatment option.

The study indicates that telmisartan may act similarly to anti-androgen agents in prostate cancer, highlighting its unique role as a PPARgamma ligand that could provide additional therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulation of prostate cancer cell growth and PSA expression by angiotensin II receptor blocker with peroxisome proliferator-activated receptor gamma ligand like action. Ishiguro, H., Ishiguro, Y., Kubota, Y., et al.[2018]

Telmisartan, an angiotensin II receptor blocker, significantly inhibits the growth of renal cell carcinoma (RCC) cells in a concentration- and time-dependent manner, while not affecting normal proximal tubular endothelial cells.

The mechanism of action appears to involve the activation of peroxisome proliferator-activated receptor (PPAR)-γ, leading to early apoptosis and DNA fragmentation in RCC cells, suggesting Telmisartan's potential as a therapeutic option for RCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Telmisartan as a peroxisome proliferator-activated receptor-γ ligand is a new target in the treatment of human renal cell carcinoma. Funao, K., Matsuyama, M., Kawahito, Y., et al.[2013]

Abiraterone acetate, a CYP17A1 inhibitor, has shown significant efficacy in treating metastatic castration-resistant prostate cancer (mCRPC) with extensive visceral involvement, even in patients heavily pretreated with chemotherapy.

In two reported cases, patients experienced major responses within one month, including regression of visceral metastases and decreased prostate-specific antigen levels, with clinical benefits lasting at least 6 months and good tolerability of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metastatic castration-resistant prostate cancer: two case reports of dramatic response with abiraterone acetate in patients heavily pretreated with chemotherapy. Dupuy, L., Long, J., Ranchoup, Y.[2021]

In a study of 8,253 prostate cancer patients followed for a median of 7.6 years, overall use of antihypertensive drugs was linked to an increased risk of prostate cancer-specific death, suggesting caution in their use.

However, angiotensin II type 1 receptor (ATr) blockers were associated with improved survival rates after prostate cancer diagnosis, indicating a potential anti-cancer effect that warrants further investigation in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antihypertensive drug use and prostate cancer-specific mortality in Finnish men. Siltari, A., Murtola, TJ., Talala, K., et al.[2020]

Docetaxel remains the standard treatment for metastatic castration-resistant prostate cancer, but there is a critical need for new therapies due to its limited survival benefits.

Recent advancements have led to the development of various targeted therapies, including mTOR inhibitors and EGFR inhibitors, which are currently being tested in clinical trials to improve treatment outcomes for this aggressive form of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel targeted therapeutics for metastatic castration-resistant prostate cancer. Antonarakis, ES., Carducci, MA., Eisenberger, MA.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3445905/

Telmisartan inhibits human urological cancer cell growth ... Telmisartan caused marked growth inhibition in the urological cancer cells in a dose- and time-dependent manner. Urological cancer cells treated with 100 μM ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/18636189/

Telmisartan is a potent target for prevention and treatment ... Recent studies have reported that ARBs have the potential to inhibit the growth of prostate cancer (PC) cells. Moreover, it was recently reported that ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06168487

NCT06168487 | Telmisartan in Prostate Cancer 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 ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0014299916300401

Increase of human prostate cancer cell (DU145) apoptosis ... The results showed that telmisartan (0–80 µm) dose-dependently reduced DU145 cell survival. Flow cytometry demonstrated cancer cell cycle arrest with increase ...

5. withpower.com withpower.com/trial/early-phase-1-prostatic-neoplasms-2024-e69c3

Telmisartan for Prostate Cancer Telmisartan is unique in treating prostate cancer because it is primarily used for managing high blood pressure and not typically associated with cancer ...

6. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0263461

Risk of cancer with angiotensin-receptor blockers increases ... The current study shows that risk of cancer with ARBs increases with increasing exposure at a trial-level. This relationship at least partially ...

7. academic.oup.com academic.oup.com/ajh/article-abstract/29/12/1358/2708298

Use of Telmisartan and the Incidence of Cancer Compared with other ARBs, telmisartan use was not associated with an increased risk of cancer overall (16.3 vs. 15.0 per 1,000 person-years, respectively; ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5863774/

The Use of Telmisartan and the Incidence of Cancer - PMC A meta-analysis reported an 8% increased risk of cancer with the use of angiotensin receptor blockers (ARBs), but subsequent meta-analyses and observational ...