Relugolix vs Leuprolide for Prostate Cancer

(REVELUTION Trial)

Not currently recruiting at 3 trial locations

Overseen By Sagar A. Patel, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Emory University

Disqualifiers: Metastatic prostate cancer, Chemotherapy, others

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

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how prostate cancer treatments affect the heart. It compares two hormone therapies, leuprolide (also known as Lupron, Eligard, or Viadur) and relugolix (also known as Orgovyx, Relumina, or Myfembree), both administered alongside radiation, to determine if relugolix might be gentler on the heart. The goal is to understand the heart risks of these treatments and identify predictors for those who might be affected. Men with localized prostate cancer, who plan to undergo radiation therapy and have not previously received hormone therapy or chemotherapy, might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that leuprolide, a common treatment for prostate cancer, is generally safe. One study found that about 10.2% of patients taking leuprolide experienced heart-related issues over a year, indicating that while some patients had heart problems, many did not.

Relugolix, a newer treatment, reduced the risk of heart-related issues by 54% compared to leuprolide, suggesting it might be gentler on the heart. Common side effects of relugolix include hot flashes, tiredness, and muscle aches, but these are usually manageable.

Both treatments are used safely in medical settings, with relugolix potentially being a safer choice for those concerned about heart health. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatment for prostate cancer, which often includes hormone therapies like leuprolide, relugolix is an oral medication that targets the same hormone pathway but with a different mechanism. While leuprolide is an injection that works by gradually lowering testosterone levels, relugolix directly blocks the receptors responsible for testosterone production, potentially leading to faster and more consistent hormone suppression. This oral administration method also offers greater convenience and potentially fewer side effects compared to injections, making it an exciting alternative for patients and researchers alike.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

In this trial, participants will receive different treatment combinations. Previous studies have shown impressive results for prostate cancer when combining leuprolide with radiation therapy. Specifically, patients who received both treatments had a survival rate of 98% over eight years, compared to 92% with only radiation. Research also indicates that 74% of patients remained free of clinical disease for five years with both treatments, compared to 40% with just radiation.

Another arm of this trial will evaluate relugolix in combination with radiation therapy. Studies have demonstrated that relugolix effectively lowers testosterone levels in prostate cancer patients, with over 98% achieving the desired testosterone reduction. Relugolix is considered safe and effective when used with radiation therapy, offering a promising alternative with potentially fewer heart-related side effects. ^{6 7 8 9 10}

Who Is on the Research Team?

Sagar A. Patel, MD

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Are You a Good Fit for This Trial?

This trial is for men aged 18 or older with localized, non-metastatic prostate cancer who are planning to receive curative-intent pelvic radiation therapy, with or without androgen deprivation therapy (ADT). Men who have had chemotherapy, immunotherapy, prior ADT, or have metastatic prostate cancer needing more than 24 months of ADT cannot participate.

Inclusion Criteria

I am scheduled for radiation therapy aimed at curing my pelvic cancer, with or without hormone therapy.

My prostate cancer has not spread to other parts of my body.

My prostate cancer has returned but hasn't spread to other parts.

Exclusion Criteria

I have previously received chemotherapy or immunotherapy.

My prostate cancer needs hormone therapy for more than 24 months.

I have been treated with hormone therapy for cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Patients undergo definitive radiation therapy in the absence of disease progression or unacceptable toxicity

6 to 24 months

Hormone Therapy

Patients receive either leuprolide or relugolix as part of androgen deprivation therapy

6 to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cardiovascular events and testosterone levels

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Leuprolide
• Radiation therapy
• Relugolix

Trial Overview The study compares the effects of two hormone therapies on heart health in men receiving radiation for prostate cancer. Leuprolide, a standard treatment with known cardiac risks is being compared against Relugolix, a newer FDA-approved drug that may be less harmful to the heart.

How Is the Trial Designed?

Group I: Arm III (radiation therapy plus relugolix) Experimental Treatment 2 Interventions

Patients undergo radiation therapy as in Arm I and receive relugolix PO QD. Treatment continues for 6 to 12 months (depending on risk) in the absence of disease progression or unacceptable toxicity.

Group II: Arm II (radiation therapy plus leuprolide) Experimental Treatment 2 Interventions

Patients undergo radiation therapy as in Arm I and receive leuprolide SC or IM every 3 or 6 months. Treatment continues for 6 to 12 months (depending on risk) in the absence of disease progression or unacceptable toxicity.

Group III: Arm I (radiation therapy alone) Active Control 1 Intervention

Patients undergo definitive radiation therapy alone (IMRT, SBRT, proton therapy, brachytherapy) in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Lupron for:

• Advanced prostate cancer
• Endometriosis
• Uterine leiomyomata
• Central precocious puberty

Approved in European Union as Eligard for:

• Advanced prostate cancer
• Endometriosis
• Uterine leiomyomata
• Central precocious puberty

Approved in Canada as Viadur for:

• Advanced prostate cancer

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Prostate Cancer Foundation

Collaborator

Trials

52

Recruited

3,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.388

Fifteen-year outcomes of external radiation with or without ... Conclusions: After 15 years of follow-up, IRPC treated with EBRT with or without 6 months of NADT experienced a high PCSS of 91%, despite a very ...

2. urotoday.com urotoday.com/library-resources/prostate-cancer-active-surveilance/140265-radiotherapy-in-prostate-cancer-concurrent-use-of-systemic-therapy-with-radiotherapy-in-localized-and-locally-advanced-disease.html

Radiotherapy in Prostate Cancer: Concurrent Use of ... showed that 5-year clinical disease-free survival was 40% (95% CI 32-48) in the radiotherapy-alone group and 74% (95% CI 67-81) in the combined-treatment group ...

3. advancesradonc.org advancesradonc.org/article/S2452-1094(22)00048-3/fulltext

Addition of Enzalutamide to Leuprolide and Definitive ... Here we present results from a phase 2 trial designed to determine the safety, tolerability, and efficacy of adding enzalutamide to standard androgen ...

4. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2815669

Efficacy and Safety of Radiotherapy Plus Relugolix in Men ... The results of these 2 randomized clinical trials suggest that relugolix rapidly achieves sustained castration in patients with localized and advanced prostate ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3004567/

Radiotherapy combined with hormonal therapy in prostate ... The disease-specific survival rate at 8 years for patients treated with hormones and radiation was 98%, compared with 92% for those treated with radiation alone ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8899139/

ELIGANT: a Phase 4, interventional, safety study of ... The results of the ELIGANT study demonstrate that ELIGARD® 22.5 mg has an acceptable safety profile in men with hormone-dependent prostate cancer in Asia. There ...

7. eligardhcp.com eligardhcp.com/proven-efficacy-safety/

ELIGARD® (Leuprolide Acetate) | Efficacy in Prostate Cancer A WELL-ESTABLISHED SAFETY PROFILE ... A single event reported as moderate pain resolved within 2 minutes and all 3 mild pain events resolved ...

8. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.056810

Cardiovascular Safety of Degarelix Versus Leuprolide in ... Over 12 months, primary outcome event rates were projected to be 5.1% for degarelix and 10.2% for leuprolide. Under this assumption, an ...

9. pfizer.com pfizer.com/news/press-release/press-release-detail/xtandir-plus-leuprolide-reduced-risk-death-40-vs-leuprolide

XTANDI® Plus Leuprolide Reduced Risk of Death by 40% ... The probability of survival at 8 years was an unprecedented 78.9% with XTANDI plus leuprolide versus 69.5% with leuprolide, in men with ...

10. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35280654/

a Phase 4, interventional, safety study of leuprorelin ... The safety profile of ELIGARD® (22.5 mg) in Asian men with hormone-dependent prostate cancer is comparable to previous studies in Western regions.