Androgen Deprivation Therapy for High Blood Pressure in Prostate Cancer Patients
(ARCH Trial)
Recruiting in Palo Alto (17 mi)
Overseen byMatthew Babcock, PhD
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
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
Trial Summary
What is the purpose of this trial?This trial aims to understand why men with prostate cancer who are treated with ADT have a higher risk of heart disease. Researchers will look at whether ADT affects the nervous system or kidneys, which help control blood pressure. The goal is to find ways to prevent heart disease in these patients. Androgen deprivation therapy (ADT) has been used for prostate cancer treatment but is associated with increased cardiovascular risks.
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 data supports the effectiveness of the drug Androgen Deprivation Therapy (ADT) for high blood pressure in prostate cancer patients?
The research shows that drugs like goserelin and leuprolide, which are part of ADT, are effective in reducing testosterone levels in prostate cancer patients, which is crucial for managing the disease. However, there is no direct evidence in the provided research about their effectiveness specifically for high blood pressure.
12345Is androgen deprivation therapy (ADT) safe for humans?
Androgen deprivation therapy (ADT) for prostate cancer, which includes treatments like GnRH agonists and antagonists, has been associated with an increased risk of cardiovascular events. However, GnRH antagonists may have a lower risk of these events compared to GnRH agonists, making them potentially safer for patients with heart concerns.
13467How is the drug Androgen Deprivation Therapy (ADT) unique for treating high blood pressure in prostate cancer patients?
Androgen Deprivation Therapy (ADT) using GnRH antagonists like abarelix and degarelix is unique because it rapidly reduces testosterone levels without causing an initial surge, unlike GnRH agonists, which can temporarily increase testosterone and potentially worsen cancer activity. This rapid suppression may be beneficial for patients with cardiovascular concerns, as it avoids the initial testosterone flare associated with increased cardiovascular risk.
13589Eligibility Criteria
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.
+10 more
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.
+4 more
Trial Timeline
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
Participant Groups
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.
3Treatment groups
Active Control
Placebo Group
Group I: Prostate CancerActive Control2 Interventions
Men undergoing androgen deprivation therapy via gonadotropin releasing hormone agonist plus androgen receptor inhibitor for the treatment of prostate cancer
Group II: Healthy + ADTActive Control2 Interventions
Healthy men undergoing gonadal suppression via gonadotropin releasing hormone agonist plus androgen receptor inhibitor for 9 weeks
Group III: Healthy + PlaceboPlacebo Group1 Intervention
Healthy men undergoing placebo for 9 weeks.
Androgen receptor inhibitor is already approved in European Union, United States, European Union, United States, 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UCHealth University of Colorado HospitalAurora, CO
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Who Is Running the Clinical Trial?
University of Colorado, DenverLead Sponsor
References
[Cardiovascular risk patients under androgen deprivation therapy: Lower risk with GnRH antagonists compared to LHRH agonists?]. [2018]Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists or GnRH antagonists is the mainstay of treatment for metastatic prostate cancer (mCaP). However, ADT is associated with serious cardiovascular events. Only a few studies that directly compare the cardiovascular risk of LHRH agonists versus GnRH antagonists have been published.
Gonadotropin-releasing hormone agonists in prostate cancer: A comparative review of efficacy and safety. [2022]Androgen deprivation therapy (ADT) using gonadotropin-releasing hormone agonist (s) (GnRH-A) remains the backbone of advanced prostate cancer treatment. In this review, we assessed the efficacy, safety, and convenience of administration of various GnRH-A. All GnRH-A (goserelin, triptorelin, buserelin, histrelin, and leuprorelin) have comparable potential to suppress testosterone (T) levels (≤50 ng/dL in a month and ≤20 ng/dL in 3 months). However, goserelin has shown better efficacy in maintaining T levels ≤50 ng/dL compared with leuprolide. The incidences of T escape are lower with goserelin and leuprolide than buserelin. Goserelin also has maximum benefit in prostate-specific antigen suppression. In neoadjuvant setting, when only goserelin was used, the 10-year overall survival (OS) rate was 42.6% to 86%. When either goserelin or leuprolide was used, the 10-year OS rate was 62%. As an adjuvant to radical prostatectomy, goserelin had a 10-year survival rate of 87%, and triptorelin had an 8-year survival rate of 84.6%. Goserelin further showed an absolute survival rate of 49% when used as an adjuvant to radiotherapy. The survival rates further improved when GnRH-A are used as combined androgen blockade compared with monotherapy. The frequency and severity of adverse events (hot flushes, fatigue, sexual dysfunction) are comparable among the GnRH-A. Goserelin appears to be the most convenient of all the GnRH-A for administration. Lack of conclusive comparative evidence makes it imperative to have a holistic approach of considering the patient profile and the disease characteristics to select the appropriate GnRH-A for ADT in prostate cancer.
Comparison of single-agent androgen suppression for advanced prostate cancer. [2022]Gonadotropin-releasing hormone (GnRH) agonists are the agents of choice for achieving androgen suppression in men with advanced prostate cancer. The GnRH agonists that have been developed and marketed for prostate cancer are leuprolide, goserelin, triptorelin, and histrelin. So far, there have been few randomized studies directly comparing these single-agent therapies; however, the literature and the data on file with the Food and Drug Administration suggest that triptorelin may be more reliable than leuprolide in maintaining castration levels of serum testosterone. The clinical significance of this benefit remains to be proven.
Cardiovascular Safety of Degarelix Versus Leuprolide for Advanced Prostate Cancer: The PRONOUNCE Trial Study Design. [2022]This study will compare the incidence of major adverse cardiovascular events (MACEs) with androgen deprivation therapy (ADT) among men with advanced prostate cancer who are being treated with a gonadotropin-releasing hormone (GnRH) antagonist versus a GnRH agonist.
Abarelix and other gonadotrophin-releasing hormone antagonists in prostate cancer. [2013]Hormonal therapy is the main recommended treatment for locally advanced and metastatic prostate cancer. Luteinizing hormone-releasing hormone (LHRH) agonists, such as buserelin, goserelin, leuprorelin and triptorelin, stimulate the pituitary's gonadotrophin-releasing hormone (GnRH) receptor, ultimately leading to its de-sensitization and subsequent reduction of LH and testosterone levels. However, this reduction is accompanied by a well described increase or 'surge' in LH and testosterone levels, necessitating the concomitant administration of an antiandrogen to combat the potential effects of transient acceleration in cancer activity. Two pure GnRH antagonists have been developed, abarelix and degarelix, that are devoid of any agonist effect on the GnRH receptor and consequently do not result in testosterone flare. Abarelix was the first GnRH antagonist to be developed and was approved by the USA Food and Drug Administration in 2004 for the initiation of hormonal castration in advanced or metastasizing hormone-dependent prostate carcinoma, when rapid androgen suppression is necessary. Clinical data on both abarelix and degarelix show that they can produce rapid and sustained decreases in testosterone to castrate levels without the need for co-administration of an antiandrogen, and with a very low complication rate in the short term.
Gonadotropin-releasing hormone antagonist in the management of prostate cancer. [2020]Luteinizing hormone-releasing hormone (LHRH) agonist therapy to induce medical castration has become the most common form of hormonal therapy for advanced and metastatic prostate cancer. When treatment is started, LHRH agonists initially stimulate the release of LH, causing a surge in serum testosterone that can precipitate a "flare" phenomenon or worsening of disease, particularly in patients with bone metastatic disease. Gonadotropin-releasing hormone (GnRH) receptor antagonism represents a newer approach to medical castration. Abarelix is a pure GnRH receptor antagonist that is devoid of any LHRH agonist activity. Results from 1 phase II and 3 phase III clinical trials demonstrate that abarelix produces medical castration more quickly and without causing testosterone surge, as compared with LHRH agonists with or without a nonsteroidal antagonist. The safety profile in terms of adverse events is comparable between the 2 types of treatment, but the lack of testosterone surge with abarelix might confer a safety advantage by abolishing the risk of a disease flare.
[Cardiovascular risk of androgen deprivation therapy for treatment of hormone-dependent prostate cancer : Differences between GnRH antagonists and GnRH agonists]. [2018]Several studies have indicated that reduction of testosterone levels in patients with prostate cancer undergoing androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists can be associated with an increased risk of cardiovascular events. The GnRH antagonists have a different mode of action compared with GnRH agonists and may be preferred in ADT for patients with cardiovascular disease.
Comparison of Surgical or Medical Castration-Related Cardiotoxicity in Patients with Prostate Cancer. [2022]Androgen deprivation therapy (ADT) includes bilateral orchiectomy or long-acting gonadotropin-releasing hormone (GnRH) agonists/antagonists. It remains controversial with respect to ADT associated cardiovascular outcomes. Hereby, we compared the risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with prostate cancer receiving either surgical castration or GnRH therapies.
Cardiovascular Toxicity of Androgen Deprivation Therapy. [2021]Androgen deprivation therapy (ADT) is the standard of care for the treatment of advanced prostate cancer (PC). ADT, particularly with GnRH agonists, leads to increased risk of cardiovascular disease, including myocardial infarction, hypertension, and stroke. This review discusses the options of ADT, the mechanism of ADT-associated cardiovascular side effects, and potential benefit by using GnRH antagonists.