Androgen Deprivation Therapy for High Blood Pressure in Prostate Cancer Patients

(ARCH Trial)

Overseen By Matthew Babcock, PhD

Age: 18+

Sex: Male

Trial Phase: Phase 4

Sponsor: University of Colorado, Denver

Must be taking: GnRH agonist, AR inhibitor

Must not be taking: Antihypertensives, Lipid-lowering, Antioxidants, Corticosteroids

Disqualifiers: Liver, Kidney, Cardiac, Diabetes, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 9 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand why high blood pressure often occurs in men receiving androgen deprivation therapy (ADT) for prostate cancer. Prostate cancer is common, and ADT serves as a primary treatment, but it can increase the risk of heart disease. The study will explore whether issues with the nervous system or kidneys, which help control blood pressure, contribute to this risk. Healthy men and those with recently diagnosed prostate cancer planning to start ADT, who don't take heart-related or hormone medications, might be a good fit. As a Phase 4 trial, the treatment has already received FDA approval and proven effective, and research helps understand how it benefits more patients.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications, such as antihypertensives, lipid-lowering medications, antioxidant vitamins, corticosteroids, and anti-inflammatory medications, for four weeks before the study starts.

What is the safety track record for these treatments?

Research shows that androgen deprivation therapy (ADT) is often used for prostate cancer, but it may be linked to heart-related issues. Studies have found that ADT might lead to high blood pressure and other heart problems. For instance, certain drugs used in ADT, such as androgen receptor inhibitors and gonadotropin-releasing hormone (GnRH) agonists, have been connected to a higher risk of heart issues.

Specifically, some research on GnRH agonists suggests they might lower blood pressure in some cases, but concerns about serious heart problems remain. The FDA has not yet determined if GnRH agonists increase the risk of heart problems or diabetes.

In summary, while ADT effectively treats prostate cancer, safety concerns exist, particularly regarding heart health. This trial is in a later phase, indicating that a good amount of safety information is already available. However, discussing any concerns with a healthcare provider before joining a trial is always advisable. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because they combine an androgen receptor inhibitor with a gonadotropin-releasing hormone agonist to tackle high blood pressure in prostate cancer patients. Unlike standard treatments that often focus solely on managing cancer symptoms, this combination targets hormone pathways that could influence blood pressure. By suppressing androgen production, this approach not only addresses cancer progression but also holds potential for cardiovascular benefits, presenting a dual-action strategy that could improve overall patient outcomes.

What evidence suggests that this trial's treatments could be effective for high blood pressure in prostate cancer patients?

Research has shown that androgen deprivation therapy (ADT) effectively treats prostate cancer. ADT uses medications to block male hormones that promote cancer growth. It serves as the main treatment for advanced prostate cancer by reducing these hormone levels. In this trial, one group of participants with prostate cancer will receive ADT through a combination of gonadotropin-releasing hormone agonists and androgen receptor inhibitors. Another group of healthy participants will receive the same ADT regimen, while a third group of healthy participants will receive a placebo. Concerns exist about side effects, such as an increased risk of heart problems, including high blood pressure. Despite these risks, ADT remains a key method for managing prostate cancer. Understanding these side effects is crucial for improving patient care and outcomes. ^{2 3 4 6 7}

Who Is on the Research Team?

Matthew Babcock, PhD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

This trial is for men aged 40+ with normal blood pressure and testosterone levels, who are either healthy or have non-metastatic prostate cancer planning to undergo ADT. Participants should not smoke, take certain medications, or have diabetes, severe kidney disease, heart conditions, nervous system diseases, high Gleason scores (≥8), or thyroid dysfunction.

Inclusion Criteria

Your blood pressure should not be lower than 140/90 mmHg when measured at rest.

Your blood sugar level should be below 126 mg/dL after fasting.

My prostate cancer has a Gleason score of 7 or less.

Exclusion Criteria

I have a current liver condition.

I have kidney issues with high creatinine and protein in my urine.

I have diabetes, an ongoing infection, or a nervous system condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo androgen deprivation therapy or placebo for 9 weeks to study its effects on blood pressure and related physiological parameters

9 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Androgen receptor inhibitor
• Gonadotropin-Releasing Hormone Agonist
• Placebo

Trial Overview The study investigates how ADT for prostate cancer may lead to high blood pressure by affecting the nervous system and kidneys. It involves a Gonadotropin-Releasing Hormone Agonist and Androgen receptor inhibitor versus placebo in controlling blood pressure.

How Is the Trial Designed?

Group I: Prostate Cancer Active Control 2 Interventions

Men undergoing androgen deprivation therapy via gonadotropin releasing hormone agonist plus androgen receptor inhibitor for the treatment of prostate cancer

Group II: Healthy + ADT Active Control 2 Interventions

Healthy men undergoing gonadal suppression via gonadotropin releasing hormone agonist plus androgen receptor inhibitor for 9 weeks

Group III: Healthy + Placebo Placebo Group 1 Intervention

Healthy men undergoing placebo for 9 weeks.

Androgen receptor inhibitor is already approved in European Union, United States for the following indications:

Approved in European Union as Androgen Deprivation Therapy for:

• Prostate cancer

Approved in United States as Androgen Deprivation Therapy for:

• Prostate cancer

Approved in European Union as Abiraterone for:

• Metastatic castration-resistant prostate cancer

Approved in United States as Abiraterone for:

• Metastatic castration-resistant prostate cancer

Approved in European Union as Enzalutamide for:

• Metastatic castration-resistant prostate cancer

Approved in United States as Enzalutamide for:

• Metastatic castration-resistant prostate cancer

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Published Research Related to This Trial

Gonadotropin-releasing hormone (GnRH) agonists, including leuprolide, goserelin, triptorelin, and histrelin, are effective for androgen suppression in men with advanced prostate cancer.

Preliminary data suggests that triptorelin may be more effective than leuprolide in maintaining low testosterone levels, although further studies are needed to confirm the clinical importance of this finding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of single-agent androgen suppression for advanced prostate cancer. Lepor, H.[2022]

The PRONOUNCE trial is a significant study involving approximately 900 men with advanced prostate cancer and pre-existing cardiovascular disease, comparing the cardiovascular safety of the GnRH antagonist degarelix versus the GnRH agonist leuprolide over 12 months.

This study aims to determine if using a GnRH antagonist reduces the risk of major adverse cardiovascular events (MACEs) compared to a GnRH agonist, addressing concerns about increased cardiovascular risks associated with androgen deprivation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular Safety of Degarelix Versus Leuprolide for Advanced Prostate Cancer: The PRONOUNCE Trial Study Design. Melloni, C., Slovin, SF., Blemings, A., et al.[2022]

GnRH antagonists are associated with a lower risk of cardiovascular events compared to GnRH agonists in prostate cancer patients undergoing androgen deprivation therapy (ADT), especially in those with cardiovascular risk factors.

The different mechanisms of action between GnRH agonists and antagonists may explain the reduced cardiovascular risk, suggesting that GnRH antagonists should be preferred for prostate cancer patients with cardiovascular issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cardiovascular risk of androgen deprivation therapy for treatment of hormone-dependent prostate cancer : Differences between GnRH antagonists and GnRH agonists]. Tschöpe, C., Kherad, B., Spillmann, F., et al.[2018]

GnRH antagonists like abarelix and degarelix provide a rapid and sustained decrease in testosterone levels for patients with advanced prostate cancer without causing the testosterone surge associated with LHRH agonists, making them effective for immediate androgen suppression.

Both abarelix and degarelix have shown a low complication rate in the short term, indicating they are a safe option for initiating hormonal therapy in hormone-dependent prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abarelix and other gonadotrophin-releasing hormone antagonists in prostate cancer. Kirby, RS., Fitzpatrick, JM., Clarke, N.[2013]

GnRH antagonists significantly reduce cardiovascular risk compared to LHRH agonists in patients undergoing androgen deprivation therapy for metastatic prostate cancer, with a hazard ratio of 0.597, indicating a 40% lower risk.

Patients with pre-existing cardiovascular conditions benefit even more, showing a 56% lower risk of cardiovascular events when treated with GnRH antagonists compared to LHRH agonists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cardiovascular risk patients under androgen deprivation therapy: Lower risk with GnRH antagonists compared to LHRH agonists?]. Merseburger, AS., Sedding, D., Hüter, K.[2018]

Abarelix, a GnRH receptor antagonist, provides a faster medical castration for advanced prostate cancer without the initial testosterone surge associated with LHRH agonists, which can worsen the disease, especially in patients with bone metastases.

The safety profile of abarelix is similar to that of LHRH agonists, but its lack of testosterone surge may offer a significant safety advantage by eliminating the risk of disease flare during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gonadotropin-releasing hormone antagonist in the management of prostate cancer. Debruyne, FM.[2020]

Androgen deprivation therapy (ADT) is the standard treatment for advanced prostate cancer, but GnRH agonists used in ADT are associated with a higher risk of cardiovascular diseases such as heart attacks and strokes.

Recent studies, including a phase III trial of the oral GnRH antagonist relugolix, suggest that GnRH antagonists have fewer cardiovascular side effects while maintaining similar efficacy to GnRH agonists, indicating they may be a safer alternative for ADT in prostate cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular Toxicity of Androgen Deprivation Therapy. Boland, J., Choi, W., Lee, M., et al.[2021]

In a study of 9,107 prostate cancer patients over a median follow-up of 3 years, surgical castration was associated with a higher risk of acute myocardial infarction (AMI) compared to those receiving GnRH therapies, with hazard ratios indicating a 1.8-fold increase in risk.

While there were no significant differences in overall major adverse cardiovascular and cerebrovascular events (MACCEs) between the two treatment groups, the findings suggest that surgical castration may pose greater cardiac safety concerns, particularly for patients with advanced cancer (stage IV).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Surgical or Medical Castration-Related Cardiotoxicity in Patients with Prostate Cancer. Kan, WC., Hsieh, KL., Chen, YC., et al.[2022]

Goserelin, a type of gonadotropin-releasing hormone agonist (GnRH-A), is more effective than leuprolide in maintaining low testosterone levels and has the highest efficacy in suppressing prostate-specific antigen, which is crucial for monitoring prostate cancer progression.

In terms of survival rates, goserelin shows impressive outcomes, with a 10-year overall survival rate of 87% when used as an adjuvant to radical prostatectomy, highlighting its effectiveness in advanced prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gonadotropin-releasing hormone agonists in prostate cancer: A comparative review of efficacy and safety. Raja, T., Sud, R., Addla, S., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11596556/

The Effect of Androgen Deprivation Therapy on ... This paper reviews the ADT and anti-androgen treatment options for men with prostate cancer and the cardiovascular effects of these therapies.

2. ahajournals.org ahajournals.org/doi/10.1161/ATVBAHA.119.313046

Cardiovascular Effects of Androgen Deprivation Therapy in ... Studies in the past decade have raised concerns about the potential for androgen deprivation therapy to increase the risk of adverse cardiovascular events.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05700903

Contributions to Hypertension With Androgen Deprivation ... This study plans to learn more about contributors to high blood pressure in men who undergo androgen deprivation therapy (ADT) to treat prostate cancer.

4. jacc.org jacc.org/doi/10.1016/j.jaccao.2023.05.011

Cardiovascular Effects of GnRH Antagonists Compared ... Androgen deprivation therapy is the cornerstone of treatment for patients with advanced prostate cancer. Meta-analysis of small, oncology ...

5. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00148-1/fulltext

Abiraterone acetate plus prednisolone with or without ... Combining androgen deprivation therapy, abiraterone, and enzalutamide increases toxic effects but does not improve efficacy versus abiraterone plus androgen ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7047549/

Cardiovascular Effects of Androgen Deprivation Therapy in ... ADT and hypertension​​ ADT was hypothesized to lead to hypertension since androgen-deprived states were shown to increase arterial stiffness46,47. However, only ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S258893112400213X

Comparative Cardiovascular Safety of Gonadotropin ... Real-world evidence studies indicate that degarelix, compared with GnRH agonists, is associated with a modest increased risk of MACEs.