Relugolix vs Leuprolide for Prostate Cancer

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Ohio State University Comprehensive Cancer Center

Must be taking: Androgen deprivation

Must not be taking: LHRH agonists, Anti-androgens

Disqualifiers: Metastatic disease, Prior malignancy, Cardiac disease, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This phase II trial compares the effect of relugolix to leuprolide on cardiac function and performance in patients with prostate cancer. Androgen deprivation therapy (ADT) has been a key component for the treatment of advanced prostate cancer for decades. The term androgen deprivation therapy means lowering a man's testosterone. Long-term studies show that ADT may contribute to a detriment to cardiac health and predisposes men to developing cardiac diseases. Recent studies suggest that men taking relugolix for treatment of prostate cancer may have a lower risk of developing cardiovascular problems, but more studies are needed to understand this observation, and there are currently no studies reporting the direct impact of ADT (relugolix, versus the more-commonly used leuprolide) on cardiac function and outcomes. Participants will receive definitive radiotherapy for unfavorable intermediate risk prostate cancer and 6-month ADT (either relugolix or leuprolide). In addition, participants will undergo the following: 1. Comprehensive cardiac and exercise testing before and after starting ADT 2. Completion of quality-of-life questionnaires at specific intervals during the study period 3. Provide blood samples at specific intervals during the study period to test for changes in steroid levels and certain biomarkers

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on 5-alpha-reductase inhibitors, you must stop them at least 30 days before the trial, and if you have used testosterone replacement therapy, it must be stopped for at least 1 year before joining the trial.

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 4 6 7}

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

Relugolix is unique because it is an oral medication that quickly lowers testosterone levels without causing an initial surge, unlike Leuprolide, which is given as an injection. Additionally, Relugolix may have a lower risk of major heart-related side effects compared to Leuprolide. ^{1 2 3 4 5}

Research Team

Shang-Jui Wang

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

This trial is for men with prostate cancer who need hormone therapy and haven't started it yet. They should be fit enough for cardiac tests, willing to answer questionnaires, and give blood samples. Specific details on who can or cannot participate are not provided here.

Inclusion Criteria

I was diagnosed with prostate cancer less than 9 months ago.

My testosterone level was above 50 ng/dL in the last 4 months.

Various blood count requirements within 120 days prior to registration

Exclusion Criteria

I have had both testicles surgically removed.

I started hormonal therapy before signing up for this study.

High risk features including specific criteria

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 6-month ADT (either relugolix or leuprolide) and definitive radiotherapy for prostate cancer

6 months

Regular visits for ADT administration and radiotherapy

Cardiac and Exercise Testing

Comprehensive cardiac and exercise testing before and after starting ADT, including exercise-stress cardiac MRI perfusion and VO2 max testing

6 months

Testing before starting ADT and at 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits at 1, 3, and 6 months

6 months

3 visits (in-person)

Treatment Details

Interventions

• Leuprolide (Gonadotropin-Releasing Hormone (GnRH) Agonist)
• Relugolix (Gonadotropin-Releasing Hormone (GnRH) Antagonist)

Trial Overview The study compares Relugolix and Leuprolide's effects on heart health in prostate cancer patients undergoing hormone therapy. It includes MRI scans, physical tests, biospecimen collection, and uses a contrast agent during the process.

Participant Groups

Group I: Arm 2 (relugolix) Experimental Treatment 5 Interventions

Patients receive definitive therapy for prostate cancer with ADT (relugolix orally once daily for a total of 6 months) in the absence of disease progression or unacceptable toxicity and definitive radiotherapy within 90 days of starting ADT. Patients receive gadolinium-based contrast intravenously (IV) and undergo exercise-stress cardiac MRI perfusion and comprehensive exercise physiology testing before starting ADT and at 6 months after starting ADT. Patients also undergo blood and urine sample collection throughout the study, as well as completion of quality-of-life questionnaires.

Group II: Arm 1 (leuprolide) Experimental Treatment 5 Interventions

Patients receive definitive therapy for prostate cancer with ADT (leuprolide via injection once every 3 months, for a total of 6 months) in the absence of disease progression or unacceptable toxicity and definitive radiotherapy within 90 days of starting ADT. Patients receive gadolinium-based contrast intravenously (IV) and undergo exercise-stress cardiac MRI perfusion and comprehensive exercise physiology testing before starting ADT and at 6 months after starting ADT. Patients also undergo blood and urine sample collection throughout the study, as well as completion of quality-of-life questionnaires.

Leuprolide is already approved in Canada for the following indications:

Approved in Canada as Viadur for:

• Advanced prostate cancer

Who Is Running the Clinical Trial?

Ohio State University Comprehensive Cancer Center

Lead Sponsor

Trials

350

Recruited

295,000+

Sumitomo Pharmaceuticals America

Industry Sponsor

Trials

5

Recruited

300+

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 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 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]

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. England pubmed.ncbi.nlm.nih.gov

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

4. 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]

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]