Relugolix vs Leuprolide for Prostate Cancer

(REPLACE-CV Trial)

No longer recruiting at 117 trial locations

Overseen By Clinical Trials at Myovant

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Sumitomo Pharma Switzerland GmbH

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 1

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines two treatments, relugolix and leuprolide acetate, to assess their impact on the risk of major heart problems in men with prostate cancer. Participants take relugolix as a daily pill, while leuprolide is administered as an injection every few months. The trial aims to determine which treatment is safer for the heart. Participants already in the study may continue their treatment if they choose. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to potentially safer heart treatment options for prostate cancer.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications.

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

Previous studies have tested relugolix in over 1,000 men with advanced prostate cancer. The research showed that common side effects included hot flashes, tiredness, weakness, constipation, and muscle pain. These effects are important to consider when using the drug.

In contrast, leuprolide acetate has a well-known safety record. Research indicates it is generally well tolerated, with quick and lasting reduction of testosterone as a key feature. Some mild pain was reported but resolved quickly.

Both treatments have been studied extensively and are generally considered safe. However, like any medication, they may cause side effects. It's important to weigh these against the benefits when considering participation in a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Relugolix is unique because it offers a new way to treat prostate cancer through an oral administration method, unlike the standard injection-based treatments like Leuprolide acetate. This oral delivery can make the treatment process more convenient and less invasive for patients. Additionally, Relugolix works by directly inhibiting the pituitary release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which can lead to a more rapid reduction in testosterone levels compared to traditional methods. Researchers are excited about these features as they could lead to more effective and patient-friendly prostate cancer management.

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

In this trial, participants will receive either relugolix or leuprolide acetate to treat prostate cancer. Research has shown that relugolix effectively lowers testosterone levels, with studies finding that it quickly reduces and maintains low testosterone levels, with over 98% of patients reaching the desired levels. Lowering testosterone is crucial because it can help prostate cancer cells grow. Another treatment option in this trial, leuprolide acetate, also lowers testosterone to treat prostate cancer. Both treatments aim to control cancer growth by reducing testosterone, but relugolix works a bit faster. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

Men over 18 with prostate cancer who need androgen deprivation therapy for at least a year can join. They should have a history of cardiovascular disease or multiple risk factors like being over 55, hypertension, high cholesterol, smoking, or family history of heart disease. Excluded are those with recent significant heart issues, uncontrolled blood pressure, long-term hormone treatments for prostate cancer (>18 months), brain metastases, or other active cancers.

Inclusion Criteria

I am eligible for both treatments offered in the study.

Has voluntarily signed and dated the informed consent form prior to baseline visit

I can think clearly enough to answer questions and participate in study activities.

Exclusion Criteria

Metastases to brain per prior clinical evaluation

My doctor plans to change my hormone therapy drugs during the study.

Treatment with any investigational product within specified timeframes

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either relugolix or leuprolide acetate for prostate cancer treatment

12 months

Day 1; 3, 6, 9, and 12 months; and every 3 months thereafter

Discontinuation Phase

Actively enrolled patients may remain on study drug up to a period of 12 months ending Dec 2024

Up to 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Leuprolide Acetate
• Relugolix

Trial Overview The trial is testing the safety of two prostate cancer treatments: Relugolix and Leuprolide Acetate. It focuses on their effects on major cardiovascular events in patients receiving these drugs as part of their treatment plan.

How Is the Trial Designed?

Group I: Relugolix Experimental Treatment 1 Intervention

Oral relugolix 120 mg once daily with a loading dose of 360 mg on Day 1

Group II: Leuprolide Acetate Active Control 1 Intervention

Subcutaneous or intramuscular leuprolide acetate 22.5 mg 3-M depot or 45 mg 6-M injection or Leuprolide acetate injectable emulsion (42 mg injectable emulsion is not allowed)

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

Approved in United States as Eligard for:

• Prostate cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

Approved in European Union as Lupron Depot for:

• Prostate cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

Approved in Canada as Lupron for:

• Prostate cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

Approved in Japan as Leuprolide Acetate for:

• Prostate cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

Who Is Running the Clinical Trial?

Sumitomo Pharma Switzerland GmbH

Lead Sponsor

Trials

19

Recruited

6,900+

Sumitomo Pharma America, Inc.

Lead Sponsor

Trials

244

Recruited

51,500+

Jatin Shah

Sumitomo Pharma America, Inc.

Chief Medical Officer since 2024

MD from an unspecified institution

Tsutomu Nakagawa

Sumitomo Pharma America, Inc.

Chief Executive Officer since 2024

MBA from Waseda University

Myovant Sciences GmbH

Lead Sponsor

Trials

23

Recruited

12,500+

Published Research Related to This Trial

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 involving 243 prostate cancer patients, the 1- and 3-month leuprorelin acetate depot formulations significantly reduced prostate-specific antigen levels by 95% and testosterone levels by 94% after a median follow-up of 132 days, indicating strong efficacy in managing advanced prostate cancer.

The treatment was well tolerated, with 90% of physicians rating the overall safety and tolerability as good or excellent, despite 37.86% of patients experiencing some treatment-emergent adverse events, primarily related to injection sites and hot flushes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of 1- and 3-month leuprorelin acetate depot formulations (Eligard(®)/Depo-Eligard(®)) for advanced prostate cancer in daily practice: a Belgian prospective non-interventional study. Braeckman, J., Michielsen, D.[2021]

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]

In a study involving 1,906 patients with advanced prostate cancer, both 3-month and 6-month leuprorelin acetate depot formulations significantly reduced prostate-specific antigen (PSA) levels from an average of 12.0 ng/mL to 0.5 ng/mL after 12 months, indicating effective treatment.

The treatment was well-tolerated, with only 8.8% of patients experiencing adverse events, suggesting that leuprorelin acetate is a safe option for managing advanced prostate cancer in routine clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Tolerability of Leuprorelin Acetate (Eligard®) in Daily Practice in Germany: Pooled Data from 2 Prospective, Non-Interventional Studies with 3- or 6-Month Depot Formulations in Patients with Advanced Prostate Cancer. Ohlmann, CH., Gross-Langenhoff, M.[2018]

In a 6-month study involving 117 patients with prostate cancer, the 3-month subcutaneous depot of leuprolide acetate (LA-2550) effectively suppressed serum testosterone levels to below 50 ng/dl in 98% of patients by day 28, and all patients achieved this level by day 35.

The treatment was well-tolerated, with no flare reactions and minimal adverse effects, primarily mild to moderate hot flashes, indicating a favorable safety profile while achieving significant reductions in testosterone and prostate-specific antigen levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical study of 22.5 mg. La-2550: A new subcutaneous depot delivery system for leuprolide acetate for the treatment of prostate cancer. Chu, FM., Jayson, M., Dineen, MK., et al.[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]

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 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]

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 ... This study aims to provide evidence on the safety, effectiveness, treatment patterns, disease course, and patient outcomes with relugolix.” In ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/22025196/

Efficacy and safety of leuprolide acetate 6-month depot for ... Leuprolide acetate 45 mg 6-month depot demonstrated rapid and sustained testosterone suppression through 12 months and was well tolerated.

7. lupronprostatecancer.com lupronprostatecancer.com/about-lupron-depot/results-with-lupron-depot

Study Results With LUPRON DEPOT In clinical trials, testosterone was suppressed in 93% of men taking the 6-month dose, 94% of men taking the 4-month dose, 95% of men taking the 3-month dose.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01415960

Efficacy and Safety of Leuprolide Acetate 22.5 mg Depot in ... Leuprolide Acetate 22.5 mg Depot is a microencapsulated formulation of leuprolide which is released slowly over time and effectively reduces testosterone levels ...

9. 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 ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2697591/

Six-month depot formulation of leuprorelin acetate in the ... Recently, a 6-month depot leuprorelin has been approved for use in advanced and metastatic prostate cancer patients. With similar efficacy and side effect ...