Relugolix + Abiraterone Acetate vs Leuprolide + Abiraterone Acetate for Prostate Cancer

Recruiting at 3 trial locations

Overseen By Bill Zheng, BS

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Emory University

Must be taking: Androgen deprivation therapy

Disqualifiers: Metastatic cancer, Prior ADT, others

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: 5

Duration: 24 months

72 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase III/IV trial compares the impact of leuprolide and abiraterone acetate (AA) versus relugolix and AA on the heart in hormone-naive patients with advanced prostate cancer receiving pelvic radiation therapy. Leuprolide is in a class of medications called gonadotropin-releasing hormone agonists (GNRHa). It prevents the body from making luteinizing hormone-releasing hormone (LHRH) and luteinizing hormone (LH). This causes the testicles to stop making testosterone (a male hormone) in men and may stop the growth of prostate tumor cells that need testosterone to grow. Abiraterone acetate, an androgen biosynthesis inhibitor, works by decreasing the amount of certain hormones in the body. Relugolix, a GNRH antagonist, works by decreasing the amount of testosterone produced by the body. This may slow or stop the spread of prostate tumor cells that need testosterone to grow. The use of hormone therapy with radiation therapy has been shown to improve survival, however, studies have suggested that the addition of hormone therapy may worsen heart (cardiac) disease and high blood pressure. In fact, studies have shown that the most common cause of death in prostate cancer patients is due to heart disease or heart attacks. Computed tomography (CT) scans create a series of detailed pictures of areas inside the body; the pictures are created by a computer linked to an x-ray machine. In this study, sophisticated cardiac CT images are used to take pictures of patients' heart and coronary arteries to help assess damage to the heart. Using cardiac CT and blood tests, this trial may help doctors determine which patients are at risk of cardiac disease when treated with combination hormone therapy, as well as the differential risk of leuprolide versus relugolix in combination with abiraterone acetate.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Abiraterone Acetate for prostate cancer?

Research shows that Abiraterone Acetate can significantly prolong survival in patients with metastatic castration-resistant prostate cancer, especially when used after chemotherapy, and it is associated with better outcomes in African American men compared to non-Hispanic White men. ^{1 2 3 4 5}

Is the combination of Relugolix and Abiraterone Acetate safe for humans?

Abiraterone Acetate is generally well-tolerated, but it can cause liver function abnormalities and issues related to mineralocorticoids (hormones that help control blood pressure and balance of fluids and electrolytes). ^{1 3 5 6 7}

How does the drug Relugolix + Abiraterone Acetate differ from other prostate cancer treatments?

Relugolix is an oral medication that lowers testosterone levels, unlike leuprolide, which is typically given as an injection. This makes Relugolix + Abiraterone Acetate a unique combination for prostate cancer treatment, offering a non-invasive option compared to traditional injectable therapies. ^{2 3 5 8 9}

Research Team

Sagar A. Patel, MD

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Eligibility Criteria

This trial is for hormone-naive men with advanced prostate cancer who will receive pelvic radiation therapy. Participants should not have a history of heart disease or high blood pressure due to the potential impact of hormone therapy on cardiac health.

Inclusion Criteria

I am scheduled for radiation therapy aimed at curing my pelvic cancer.

My prostate cancer has not spread to other parts of my body.

My prostate cancer has returned but hasn't spread to other parts.

Exclusion Criteria

My prostate cancer has spread and needs ongoing hormone therapy or chemotherapy.

I have been treated with hormone therapy for cancer.

I have had heart bypass surgery or a procedure to open my heart's arteries.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either leuprolide plus abiraterone acetate with prednisone or relugolix plus abiraterone acetate with prednisone, along with standard of care radiation therapy, for up to 24 months

24 months

Injections every 3 to 6 months, daily oral medication

Follow-up

Participants are monitored for safety and effectiveness after treatment, including serum testosterone measurement at 30 and 60 days

2 months

2 visits (in-person)

Cardiac Monitoring

Participants undergo pre-treatment and 12-month coronary computed tomography angiography (CCTA) and blood sample collection to assess cardiac health

12 months

Treatment Details

Interventions

• Abiraterone Acetate
• Leuprolide
• Relugolix

Trial Overview The study compares two hormonal treatments: leuprolide plus abiraterone acetate versus relugolix plus abiraterone acetate, assessing their effects on the heart using advanced CT imaging and blood tests.

Participant Groups

Group I: Arm II (relugolix + abiraterone acetate/prednisone) Experimental Treatment 6 Interventions

Patients receive oral relugolix daily plus oral abiraterone acetate (AA) with prednisone daily for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo standard of care radiation therapy.

Group II: Arm I (leuprolide plus abiraterone acetate/prednisone) Experimental Treatment 7 Interventions

Patients receive leuprolide IM or SC injections every 3 to 6 months plus oral abiraterone acetate (AA) with prednisone daily for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo standard of care radiation therapy.

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?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Sumitomo Pharma America, Inc.

Industry 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

National Comprehensive Cancer Network

Collaborator

Trials

121

Recruited

7,400+

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

Findings from Research

In a study of 3808 men with metastatic castration-resistant prostate cancer (mCRPC), African American men receiving first-line abiraterone therapy had a significantly higher median overall survival (23 months) compared to non-Hispanic White men (17 months).

The study found no overall survival difference between first-line abiraterone and enzalutamide for African American men, while non-Hispanic White men had decreased survival with abiraterone compared to enzalutamide, suggesting that race may influence treatment outcomes in mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes Among African American and Non-Hispanic White Men With Metastatic Castration-Resistant Prostate Cancer With First-Line Abiraterone. Marar, M., Long, Q., Mamtani, R., et al.[2022]

In a study of 58 elderly patients with metastatic castration-resistant prostate cancer (mCRPC), non-adherence rates to the treatments abiraterone and enzalutamide were low at 4.8% overall, indicating good adherence among this population.

Non-adherence was linked to patients' frailty and their radiological response to treatment, suggesting that geriatric assessments could help identify at-risk patients and improve adherence to these important cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence to abiraterone or enzalutamide in elderly metastatic castration-resistant prostate cancer. Banna, GL., Urzia, V., Benanti, C., et al.[2021]

In a multicenter early-access trial involving 2314 patients with metastatic castration-resistant prostate cancer, abiraterone acetate combined with prednisone showed a median time to PSA progression of 8.5 months and a median time to clinical progression of 12.7 months, indicating its efficacy in delaying disease progression after chemotherapy.

The study reported that 41% of patients experienced grade 3 or 4 treatment-related adverse events, with hepatotoxicity and hypertension being the most common, but no new safety signals were identified, suggesting that abiraterone acetate is generally safe for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate for patients with metastatic castration-resistant prostate cancer progressing after chemotherapy: final analysis of a multicentre, open-label, early-access protocol trial. Sternberg, CN., Castellano, D., Daugaard, G., et al.[2022]

A study of 368 patients with metastatic castration-resistant prostate cancer (mCRPC) found five key risk factors that can predict overall survival (OS) after starting abiraterone acetate treatment, including low hemoglobin levels and high number of metastases.

Using these risk factors, patients can be categorized into three groups based on their prognosis, with median survival times ranging from 22.6 months for those with fewer risk factors to just 6.2 months for those with more, helping guide treatment decisions and patient counseling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Which Factors Predict Overall Survival in Patients With Metastatic Castration-Resistant Prostate Cancer Treated With Abiraterone Acetate Post-Docetaxel? Van Praet, C., Rottey, S., Van Hende, F., et al.[2018]

Abiraterone acetate (AA) is effective and well tolerated in men with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC), showing a 49% rate of PSA decline of 50% or more at 12 weeks in a study of 145 patients.

The median progression-free survival was 17 months and overall survival was 26.5 months, with outcomes significantly influenced by factors such as pain presence, patient satisfaction, and PSA levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of abiraterone acetate in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: an Italian multicenter "real life" study. Cindolo, L., Natoli, C., De Nunzio, C., et al.[2022]

In a study of 93 post-chemotherapy patients with metastatic castration-resistant prostate cancer, the median time to treatment failure (TTF) for abiraterone acetate therapy was 9.8 months, indicating its effectiveness in prolonging survival.

Patients with well-controlled hypertension, stable coronary artery disease, and those using angiotensin system inhibitors (ASi) experienced significantly longer TTF, with ASi users having a median TTF of 12.2 months compared to 5.8 months for non-users, suggesting that ASi may enhance the efficacy of ABI therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Angiotensin System Inhibitors May Improve Outcomes of Patients With Castration-Resistant Prostate Cancer During Abiraterone Acetate Treatment-A Cardio-Oncology Study. Wilk, M., Waśko-Grabowska, A., Skoneczna, I., et al.[2022]

Abiraterone acetate is an effective treatment for metastatic castration-resistant prostate cancer (mCRPC), showing significant improvements in survival and progression-free survival in chemotherapy-naïve patients, as demonstrated in the COU-AA-302 trial.

While abiraterone is generally well-tolerated, it can cause liver function abnormalities and mineralocorticoid-related side effects, highlighting the importance of monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone in the management of castration-resistant prostate cancer prior to chemotherapy. Gartrell, BA., Saad, F.[2020]

In a phase 3 trial with 1088 patients, abiraterone acetate plus prednisone significantly improved overall survival compared to placebo plus prednisone, with a median survival of 34.7 months versus 30.3 months, indicating its efficacy in treating chemotherapy-naive castration-resistant prostate cancer.

The treatment was associated with a manageable safety profile, although there were some increased risks of grade 3-4 adverse events, such as cardiac disorders and elevated liver enzymes, suggesting that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Ryan, CJ., Smith, MR., Fizazi, K., et al.[2022]

In a phase II trial involving 70 men with high-risk localized prostate cancer, adding cabazitaxel to neoadjuvant therapy with abiraterone acetate and leuprolide acetate did not significantly improve the rates of pathologic complete response (pCR) or minimal residual disease (MRD) compared to therapy without cabazitaxel.

Patients who achieved pCR/MRD had significantly better 12-month biochemical relapse-free survival rates (96.0% vs. 62.0%), indicating that achieving these outcomes is associated with improved long-term prognosis, despite the addition of cabazitaxel not enhancing pCR/MRD rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Cabazitaxel plus Abiraterone/Leuprolide Acetate in Patients with High-Risk Prostate Cancer: ACDC-RP Phase II Trial. Fleshner, NE., Sayyid, RK., Hansen, AR., et al.[2023]

References

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

Outcomes Among African American and Non-Hispanic White Men With Metastatic Castration-Resistant Prostate Cancer With First-Line Abiraterone. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Adherence to abiraterone or enzalutamide in elderly metastatic castration-resistant prostate cancer. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Abiraterone acetate for patients with metastatic castration-resistant prostate cancer progressing after chemotherapy: final analysis of a multicentre, open-label, early-access protocol trial. [2022]

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

Which Factors Predict Overall Survival in Patients With Metastatic Castration-Resistant Prostate Cancer Treated With Abiraterone Acetate Post-Docetaxel? [2018]

5. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of abiraterone acetate in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: an Italian multicenter "real life" study. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Angiotensin System Inhibitors May Improve Outcomes of Patients With Castration-Resistant Prostate Cancer During Abiraterone Acetate Treatment-A Cardio-Oncology Study. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Abiraterone in the management of castration-resistant prostate cancer prior to chemotherapy. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. [2022]

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

Neoadjuvant Cabazitaxel plus Abiraterone/Leuprolide Acetate in Patients with High-Risk Prostate Cancer: ACDC-RP Phase II Trial. [2023]