Lisinopril for Preventing Urinary Side Effects in Prostate Cancer Radiotherapy

Overseen By Therese Smudzin

Age: 18+

Sex: Male

Trial Phase: Phase < 1

Sponsor: University of Rochester

Must not be taking: Lisinopril, RAS modifiers

Disqualifiers: Prior pelvic radiotherapy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Concurrent with radiation

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose of lisinopril for men with non-metastatic prostate cancer undergoing radiation treatment to manage urinary side effects. Although typically used to treat high blood pressure, researchers are investigating whether lisinopril can also alleviate urinary problems caused by radiation. Participants will receive either radiation alone or radiation with lisinopril to compare outcomes. Men with prostate cancer who are receiving radiation treatment and have not recently taken lisinopril or similar medications might be suitable for this study. As an Early Phase 1 trial, this research focuses on understanding lisinopril's effects in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be taking lisinopril or similar drugs within two months before joining the study.

Is there any evidence suggesting that lisinopril is likely to be safe for humans?

Research has shown that lisinopril, a medication commonly used to treat high blood pressure, is under study for its potential to alleviate urinary side effects in men undergoing radiation therapy for prostate cancer. The FDA has already approved lisinopril for other uses, confirming its well-known safety profile. Most people tolerate it well, though it can cause side effects like any medication. Common side effects may include dizziness or a cough, while serious side effects are rare. As this study is in the early stages, researchers are still determining the best dose and are carefully monitoring for any side effects. If lisinopril proves safe and effective, it could help reduce urinary problems caused by radiation therapy. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for urinary side effects from prostate cancer radiotherapy focus on managing symptoms after they occur. But Lisinopril, a blood pressure medication, is being explored for its potential to prevent these side effects altogether. Researchers are excited because Lisinopril works by protecting blood vessels and tissues from radiation damage, which could mean fewer urinary issues for patients during and after their cancer treatment. This prevention-focused approach is quite different from current options that only address symptoms after they've developed.

What evidence suggests that lisinopril might be an effective treatment for urinary side effects in prostate cancer radiotherapy?

Research has shown that lisinopril, which participants in this trial may receive, might help prevent urinary problems in men undergoing radiation treatment for prostate cancer. This medication, commonly used to lower high blood pressure, could improve blood flow to the urinary system. Improved blood flow might reduce urinary symptoms after radiation. Additionally, studies on similar drugs have demonstrated a decrease in some radiation-related side effects. While more research is needed, these early findings suggest that lisinopril could help manage urinary issues in this context. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

Men under 70 with non-metastatic prostate cancer who are set for radiation therapy at Wilmot Cancer Institute can join. They must be in good health, able to follow the study plan, have normal kidney and liver function, not have had pelvic radiotherapy before, and not be on lisinopril or similar drugs recently.

Inclusion Criteria

I've been mostly active and able to care for myself in the past 6 months.

My cancer has not spread to distant parts of my body.

I am mentally and physically able to follow the study's requirements.

Exclusion Criteria

Have had a prior allergic reaction to lisinopril

I have had radiation therapy to my pelvic area before.

I have been taking lisinopril or a similar drug in the last two months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants undergo radiation treatment for prostate cancer

6-8 weeks

Weekly visits during radiation

Treatment

Participants receive lisinopril to determine the preferred dose for preventing urinary toxicity

Concurrent with radiation

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Visits at 1 month, 3 months, 6 months, and 12 months post-radiation

What Are the Treatments Tested in This Trial?

Interventions

• Lisinopril

Trial Overview The trial is testing different doses of Lisinopril tablets to find the best one for preventing urinary problems after radiation treatment for prostate cancer. It will also look at how Lisinopril affects certain biomarkers related to these urinary symptoms.

How Is the Trial Designed?

Group I: Intervention group Experimental Treatment 1 Intervention

Group II: Control group Active Control 1 Intervention

Patients who receive radiation but no intervention

Who Is Running the Clinical Trial?

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

Medical College of Wisconsin

Collaborator

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

In a study of 115 patients at the University of Wisconsin and 186 patients at the University of Hawaii, those taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) showed a significantly higher rate of pathologic complete response (pCR) to neoadjuvant radiation therapy for rectal cancer, with a 3-fold increase in the UW cohort and a 2-fold increase in the UH cohort.

Multivariate analyses indicated that ACEI/ARB use is a strong predictor of pCR, with an odds ratio of 4.02, suggesting these medications may enhance the effectiveness of neoadjuvant radiation therapy in rectal cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased tumor response to neoadjuvant therapy among rectal cancer patients taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Morris, ZS., Saha, S., Magnuson, WJ., et al.[2022]

In a study using PC-3 human prostate cancer cells and an animal model, combining radiotherapy (RT) with naftopidil significantly delayed tumor growth more effectively than either treatment alone.

The combination therapy also suppressed the upregulation of the antioxidant enzyme manganese superoxide dismutase (MnSOD), which is often increased in response to RT, suggesting that naftopidil may enhance the effectiveness of RT by targeting protective mechanisms in cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination treatment with naftopidil increases the efficacy of radiotherapy in PC-3 human prostate cancer cells. Iwamoto, Y., Ishii, K., Kanda, H., et al.[2018]

In a study of 108 patients undergoing radical external beam radiotherapy for localized prostate cancer, the use of the α-blocker tamsulosin significantly reduced the incidence of acute urinary retention (AUR) compared to a control group, indicating its efficacy in managing radiotherapy-induced urinary symptoms.

While tamsulosin improved patient-reported symptoms, the study found no independent predictive factors to identify which patients would benefit most from the treatment, suggesting that its use should be considered selectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A-blockers for the management of lower urinary tract symptoms in patients with prostate cancer treated with external beam radiotherapy: a randomized controlled study. Tsirkas, K., Zygogianni, A., Kougioumtzopoulou, A., et al.[2021]

In a pilot study of 26 prostate cancer patients experiencing acute radiation urethritis, Flomax (tamsulosin HCl) demonstrated an initial response rate of 62% at a 0.4 mg dose, with overall urinary symptom control achieved in 77% of patients after adjusting doses.

The presence of benign prostatic hyperplasia (BPH) was a potential predictor of a better initial response to Flomax, suggesting that certain patient characteristics may influence treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tamsulosin palliates radiation-induced urethritis in patients with prostate cancer: results of a pilot study. Prosnitz, RG., Schneider, L., Manola, J., et al.[2019]

Phosphodiesterase-5 inhibitors (PDE5i) significantly improve erectile function in patients with erectile dysfunction (ED) after radiotherapy for prostate cancer, as shown by enhanced scores on the International Index of Erectile Function (IIEF) and positive responses in Global Efficacy Questions (GEQs) and Sexual Encounter Profile (SEP) diaries.

The side effects of PDE5i are mostly mild to moderate and well tolerated, making them a safe option for treatment, with headache, flushing, and dyspepsia being the most common adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phosphodiesterase-5 inhibitors could be efficacious in the treatment of erectile dysfunction after radiotherapy for prostate cancer: a systematic review and meta-analysis. Yang, L., Qian, S., Liu, L., et al.[2018]

In a study using A549 cell xenografts in athymic mice, ramipril did not change the response of tumors to radiation treatment, regardless of whether it was administered before or after radiation.

However, ramipril significantly reduced radiation injury in normal tissues, suggesting it may provide a therapeutic advantage by protecting healthy cells while not affecting tumor response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential radiation effect in tumor and normal tissue after treatment with ramipril, an angiotensin-converting enzyme inhibitor. Kohl, RR., Kolozsvary, A., Brown, SL., et al.[2013]

Prostate cancer treatments, such as GnRH agonists and enzalutamide, can increase the risk of hypertension, which is a significant cardiovascular risk factor that can lead to serious complications like heart failure and stroke.

The paper recommends individualized blood pressure targets for prostate cancer patients, suggesting a goal of 130/80 mmHg while considering other health issues like frailty and existing comorbidities to guide antihypertensive treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Intersection of Prostate Cancer and Hypertension: a Call to Action. Dolmatova, E., Waheed, N., Olson, BM., et al.[2023]

In a study of 80 early prostate cancer patients who experienced lower urinary tract symptoms (LUTS) after LDR brachytherapy, the combination of tamsulosin and low-dose sildenafil significantly improved LUTS compared to tamsulosin alone at 3 months post-implantation.

While both treatment groups showed increases in LUTS at 1 month, the combination therapy group had a statistically significant greater decrease in symptom scores at 3 months, indicating its potential effectiveness in managing post-implantation LUTS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of combination therapy with an alpha blocker and low-dose sildenafil on post-therapy lower urinary tract symptoms after low-dose-rate brachytherapy for prostate cancer. Yu, YD., Kang, MH., Choi, CI., et al.[2022]

A meta-analysis of seven randomized clinical trials involving 7347 patients found that enzalutamide, a treatment for prostate cancer, is associated with a significant risk of hypertension, with an overall incidence of 11.9%.

The risk of developing high-grade hypertension was also notable, with a relative risk of 2.27, indicating that patients on enzalutamide are more likely to experience severe hypertension compared to those not receiving the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased Risk of Hypertension with Enzalutamide in Prostate Cancer: A Meta-Analysis. Zhu, X., Wu, S.[2021]

Lisinopril significantly improved survival rates in juvenile rats exposed to acute radiation, with an 88% survival rate observed when treatment started 7 days post-irradiation, compared to 0% survival in untreated rats by 114 days.

In older rats, lisinopril also mitigated radiation nephropathy, demonstrating its potential as a treatment for delayed effects of radiation exposure across different age groups, although younger rats were found to be more sensitive to radiation injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed Effects of Acute Radiation Exposure (Deare) in Juvenile and Old Rats: Mitigation by Lisinopril. Medhora, M., Gao, F., Gasperetti, T., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05530655

NCT05530655 | A Study to Determine the Preferred Dose ... This study will establish the preferred dose of lisinopril in men with non-metastatic prostate cancer undergoing radiation treatment. This study will also ...

2. cancer.gov cancer.gov/clinicaltrials/NCI-2025-05819

Lisinopril for the Prevention of Urinary Side Effects ... This may improve blood flow to the urinary system, which may help prevent urinary side effects following radiation therapy for prostate adenocarcinoma.

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05530655/a-study-to-determine-the-preferred-dose-of-the-drug-lisinopril-for-preventing-urinary-toxicity-following-radiotherapy-for-prostate-cancer

A Study to Determine the Preferred Dose of the Drug ... This study will establish the preferred dose of lisinopril in men with non-metastatic prostate cancer undergoing radiation treatment.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11769270/

The Effect of the Concurrent Use of Angiotensin-Converting ... Conclusions: ACEI use is associated with a reduction in radiation pneumonitis, but evidence for other radiotherapy-related toxicity and survival ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0167814015002935

Dosimetry, clinical factors and medication intake ... To identify dosimetry, clinical factors and medication intake impacting urinary symptoms after prostate radiotherapy. Material and methods. Data describing ...

6. withpower.com withpower.com/trial/early-phase-1-prostate-cancer-2023-a3480

Lisinopril for Preventing Urinary Side Effects in Prostate ... This study will establish the preferred dose of lisinopril in men with non-metastatic prostate cancer undergoing radiation treatment.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10330568/

Modeling Normal Bladder Injury After Radiation Therapy - PMC Symptoms of radiotherapy-induced bladder injury for prostate cancer patients include increased urinary frequency, urinary retention, dysuria, and hematuria ...