Relugolix vs Leuprolide for Prostate Cancer

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Male

Trial Phase: Phase 2

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 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: 9

Duration: 6 months

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare relugolix and leuprolide to assess their effects on heart health in people with prostate cancer. Both treatments are used in androgen deprivation therapy, which lowers testosterone, but they may impact the heart differently. Participants will undergo heart and exercise tests and provide blood samples to monitor changes. The trial seeks individuals with prostate cancer who are scheduled for radiotherapy and have specific risk factors, such as a certain PSA level or tumor stage. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group.

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.

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

Previous studies have shown that relugolix carries about a 54% lower risk of major heart problems compared to leuprolide. Common side effects of relugolix include hot flashes, fatigue, constipation, and muscle pain. Importantly, no new safety concerns emerged when relugolix was used with radiotherapy.

Research indicates that leuprolide is generally safe, though some studies suggest it may have more heart-related issues compared to another drug, degarelix. Overall, leuprolide is considered safe for treating prostate cancer.

Both treatments are safe, but relugolix may offer better heart health benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about relugolix for prostate cancer because, unlike traditional treatments like leuprolide which require injections, relugolix is taken orally once a day. This oral administration can be more convenient and less invasive for patients. Additionally, relugolix works by directly blocking the receptors for luteinizing hormone-releasing hormone (LHRH), which may allow for a quicker reduction in testosterone levels, potentially leading to faster therapeutic effects. These features could make relugolix a promising alternative to current hormonal therapies for prostate cancer.

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

This trial will compare relugolix and leuprolide for treating prostate cancer. Studies have shown that relugolix, which participants in this trial may receive, effectively lowers testosterone levels quickly. Over 98% of patients achieved the necessary drop in testosterone, crucial for controlling prostate cancer growth. Research also suggests that relugolix might reduce the risk of heart problems compared to other treatments. Meanwhile, leuprolide, another treatment option in this trial, is also effective, with most patients experiencing a significant drop in testosterone. Both treatments have proven effective in managing prostate cancer, but relugolix might offer additional heart health benefits. ^{1 3 6 7 8}

Who Is on the Research Team?

Shang-Jui Wang

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• Leuprolide
• Relugolix

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.

How Is the Trial Designed?

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 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?

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+

Published Research Related to This Trial

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]

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 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]

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 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

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