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

Trial Summary

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.

What data supports the effectiveness of the drug Relugolix for prostate cancer?

Research shows that Relugolix is effective in lowering testosterone levels in men with advanced prostate cancer, maintaining these low levels for 48 weeks, and reducing the risk of major heart-related events compared to Leuprolide. ^{1 2 3 4 5}

Is Relugolix safe for treating prostate cancer compared to Leuprolide?

Relugolix is generally well tolerated and may have a lower risk of major heart-related issues compared to Leuprolide. Both drugs can cause side effects related to testosterone suppression, and Relugolix may also affect heart rhythm and cause harm to unborn babies. ^{1 2 3 6 7}

How does the drug Relugolix differ from Leuprolide in treating prostate cancer?

Relugolix is unique because it is an oral medication that rapidly lowers testosterone levels without causing an initial surge, unlike Leuprolide, which is given as an injection and can cause a temporary increase in testosterone. Additionally, Relugolix has been shown to reduce the risk of major heart-related side effects compared to Leuprolide. ^{1 2 3 4 5}

What is the purpose of this trial?

This study is testing the way that approved androgen deprivation therapy treatments, Leuprolide and Relugolix, for prostate cancer affect quality of life, blood levels, cholesterol, and blood sugar. The drugs are already standard treatment for people with prostate cancer, and the drugs will be used as described in their label. The names of the study drugs involved in this study are: * Leuprolide (type of ADT) * Relugolix (type of ADT)

Research Team

Alicia Morgans, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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.

Life expectancy of greater than 12 months.

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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 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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. France pubmed.ncbi.nlm.nih.gov

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

3. Switzerland 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

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

5. United States pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of androgen deprivation therapy with relugolix for the treatment of advanced prostate cancer. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of leuprolide acetate 6-month depot for suppression of testosterone in patients with prostate cancer. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

First Oral Hormone for Treating Prostate Cancer. [2023]