Relugolix vs Leuprolide for Prostate Cancer

Recruiting at 3 trial locations

Overseen By Alicia Morgans, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must be taking: ADT

Must not be taking: Second generation AR therapies

Disqualifiers: Cardiac event, Brain metastases, 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: 3

Duration: 12 months

110 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two prostate cancer treatments, Leuprolide and Relugolix, to assess their effects on quality of life and health markers such as blood sugar and cholesterol. Participants will receive either Leuprolide, an injection, or Relugolix, a pill, in a randomized manner. The study seeks individuals diagnosed with prostate cancer who have not previously received similar hormone therapies. Participants should also have certain health conditions under control, such as no recent major heart events and the ability to manage daily activities. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot have prior or planned treatment with certain prostate cancer drugs or be on other investigational agents. It's best to discuss your current medications with the trial team.

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

Research shows that both Relugolix and Leuprolide are generally well-tolerated treatments for prostate cancer. Relugolix effectively lowers testosterone levels in patients with prostate cancer. Studies have found that Relugolix reduces the risk of major heart problems by 54% compared to other treatments. It also lowers testosterone levels more quickly and allows for faster recovery after stopping treatment.

Leuprolide is a standard treatment for prostate cancer, with well-known safety. It is widely used and has proven effective for many patients.

Both drugs are approved for treating prostate cancer, indicating thorough safety testing. While some side effects may occur, most patients can generally manage these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Relugolix for prostate cancer because it works differently from the traditional hormone therapy, like Leuprolide. Unlike Leuprolide, which requires injections at a clinic, Relugolix can be taken orally at home, offering more convenience and potentially improving adherence. Additionally, Relugolix acts by directly blocking receptors involved in hormone production, which might offer a faster reduction in testosterone levels compared to the traditional approach. This could mean a quicker response and potentially better outcomes for patients managing their prostate cancer.

What is the effectiveness track record for Leuprolide and Relugolix in treating prostate cancer?

This trial will compare Relugolix and Leuprolide as treatments for prostate cancer. Research has shown that both Relugolix, which participants in this trial may receive, and Leuprolide, another treatment option in this trial, are effective. In studies, over 98% of patients taking Relugolix reached low testosterone levels, which helps slow cancer growth. It also works faster than some other treatments by quickly reducing testosterone. Leuprolide, a common treatment for prostate cancer, also lowers testosterone to help control the disease. Both drugs have proven effective in managing prostate cancer by reducing the hormones that help it grow. ^{5 6 7 8 9}

Who Is on the Research Team?

Alicia Morgans, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

Men over 18 with prostate cancer who need androgen deprivation therapy (ADT) but haven't had it before. They must be able to sign consent, have a testosterone level >200 ng/mL, good organ function, no prior GnRH treatments, and agree to use contraception. Excludes those with allergic reactions to similar drugs or recent major heart events.

Inclusion Criteria

I have another cancer, but it doesn't affect my current treatment's safety or effectiveness.

Patients must have testosterone level > 200 ng/mL prior to initiation of ADT.

Life expectancy of greater than 12 months.

Exclusion Criteria

I am allergic to medications similar to leuprolide or relugolix.

My cancer has spread to my brain.

I do not have any uncontrolled illnesses.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Leuprolide or Relugolix for prostate cancer treatment

12 months

Surveys at baseline and at months 3, 6, 9, and 12; Follow-up visits every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Leuprolide
• Relugolix

Trial Overview The trial compares the effects of two ADT medications for prostate cancer—Relugolix and Leuprolide—on quality of life, blood levels, cholesterol, and blood sugar. Participants will receive one of these standard treatments as per their labeling instructions.

How Is the Trial Designed?

Group I: Arm A: Relugolix Experimental Treatment 1 Intervention

55 participants will be randomized in a 1:1 fashion to Relugolix and stratified by intent to treat with radiation and will complete study procedures as outlined: * Surveys at baseline and at months 3, 6, 9, and 12. * Medication diary entries. * Cycles 1 - 6: --Days 1 - 28 of 28 day cycle: Predetermined dose of Relugolix. Participant will self-administer at home. * Follow up visits every 3 months for 12 months.

Group II: Arm B: Leuprolide Active Control 1 Intervention

55 participants will be randomized in a 1:1 fashion to Leuprolide and stratified by intent to treat with radiation and will complete study procedures as outlined: * Surveys at baseline and at months 3, 6, 9, and 12. * Cycle 1 and Cycle 4: --Day 1 of 28 day cycle: Predetermined dose of Leuprolide. Injection will be administered in clinic. * Follow up visits every 3 months for 12 months.

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?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Prostate Cancer Foundation

Collaborator

Trials

52

Recruited

3,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Myovant Sciences GmbH

Industry Sponsor

Trials

23

Recruited

12,500+

Published Research Related to This Trial

Relugolix (Orgovyx) is the first oral medication approved for treating advanced prostate cancer, functioning as a gonadotropin-releasing hormone receptor antagonist.

While effective, relugolix carries risks such as prolonging the QT interval and potential embryo-fetal toxicity, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First Oral Hormone for Treating Prostate Cancer. Aschenbrenner, DS.[2023]

In the phase III HERO trial, relugolix demonstrated a sustained castration rate of over 90% in men with advanced prostate cancer over 48 weeks, which was non-inferior to the traditional treatment with leuprolide, and showed potential superiority in exploratory analyses.

Relugolix is generally well tolerated and may have a lower risk of major adverse cardiac events compared to leuprolide, making it a promising oral treatment option for rapid testosterone suppression without the initial surge associated with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relugolix: A Review in Advanced Prostate Cancer. Shirley, M.[2023]

Relugolix, while effective in rapidly decreasing testosterone levels without the risk of flare, was found to be less cost-effective than leuprolide for treating advanced prostate cancer, with an incremental cost-effectiveness ratio (ICER) of $49,571.1 per quality-adjusted life-year (QALY).

Despite showing slightly better progression-free and overall survival rates at the first line of therapy (72.7% and 86.0% for relugolix compared to 61.0% and 85.9% for leuprolide), relugolix did not provide significant survival advantages over leuprolide, indicating that leuprolide remains the more economically favorable option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of androgen deprivation therapy with relugolix for the treatment of advanced prostate cancer. Adekunle, OA., Seoane-Vazquez, E., Brown, LM.[2023]

In the HERO study involving 930 men with advanced prostate cancer, 97% of those taking relugolix achieved sustained castration levels of testosterone compared to 89% of those receiving leuprolide, indicating relugolix is more effective in lowering testosterone levels.

Relugolix also led to a quicker reduction in testosterone levels and resulted in more men returning to normal testosterone levels after treatment, with side effects being similar and mostly mild or moderate for both treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plain language summary of the HERO study comparing relugolix with leuprolide for men with advanced prostate cancer. Shore, ND., Sutton, J.[2022]

In the phase 3 HERO trial involving patients with advanced prostate cancer, relugolix showed superior sustained testosterone suppression compared to leuprolide over a 48-week period.

Relugolix also allowed for faster testosterone recovery after treatment discontinuation and was associated with a 50% reduction in major adverse cardiovascular events (MACE), highlighting its potential safety benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 3 HERO Trial Finds Relugolix to Be Superior to Leuprolide in Prostate Cancer. Slater, H.[2021]

In a study involving 1074 men with advanced prostate cancer, relugolix demonstrated similar castration resistance-free survival (CRFS) rates compared to leuprolide, with rates of 74.3% and 75.3% respectively after 48 weeks of treatment.

No new safety concerns were identified with relugolix, indicating that it is a safe alternative to leuprolide for managing advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relugolix vs. Leuprolide Effects on Castration Resistance-Free Survival from the Phase 3 HERO Study in Men with Advanced Prostate Cancer. Saad, F., George, DJ., Cookson, MS., et al.[2023]

In a study of 151 men with prostate cancer, the new 6-month leuprolide acetate depot formulation achieved a 93.4% success rate in suppressing testosterone levels to ≤ 50 ng/dl, demonstrating its efficacy in hormone therapy.

The treatment was well tolerated, with sustained testosterone suppression maintained for 12 months and a significant reduction in the frequency of injections needed for patients, improving their overall treatment experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of leuprolide acetate 6-month depot for suppression of testosterone in patients with prostate cancer. Spitz, A., Young, JM., Larsen, L., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10198864/

Relugolix: A Review in Advanced Prostate Cancer - PMC In a key clinical trial in men with advanced prostate cancer, once-daily relugolix provided sustained castration in > 90% of patients, with a ...

2. 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 ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2950393025000816

Relugolix in prostate cancer therapy: Clinical evidence and ... Real-world studies performed to date have confirmed the effectiveness of relugolix, with more than 98% patients achieving castrate testosterone levels.

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2004325

Oral Relugolix for Androgen-Deprivation Therapy in ... In this trial involving men with advanced prostate cancer, relugolix achieved rapid, sustained suppression of testosterone levels that was superior to that ...

5. onclive.com onclive.com/view/optyx-study-offers-preliminary-glance-into-real-world-use-of-relugolix-in-advanced-prostate-cancer

OPTYX Study Offers Preliminary Glance Into Real-World ... Data from OPTYX showed that most patients (52.2%) in the overall population (n = 999) received relugolix in combination with other prostate ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39436909/

Adverse events analysis of Relugolix (Orgovyx®) for ... This study aims to comprehensively analyze the AEs associated with Relugolix (Orgovyx®) using data from the FAERS database, and gain a better understanding of ...

7. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0312481

Adverse events analysis of Relugolix (Orgovyx®) for prostate ... This study aims to comprehensively analyze the AEs associated with Relugolix (Orgovyx ® ) using data from the FAERS database, and gain a better understanding ...

8. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-prostate-cancer/158172-asco-gu-2025-safety-and-tolerability-of-relugolix-in-combination-with-abiraterone-or-apalutamide-for-treatment-of-advanced-prostate-cancer-data-from-a-52-week-clinical-trial.html

ASCO GU 2025: Safety and Tolerability of Relugolix in ... In this 52-week study, the oral testosterone-lowering drug relugolix was studied in patients with advanced prostate cancer in combination with ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT03085095

NCT03085095 | A Study to Evaluate the Safety and ... The purpose of this study is to determine the efficacy and safety of relugolix 120 milligrams (mg) orally once daily for 48 weeks on maintaining serum ...