Randomized Controlled Trial of Leuprolide Plus Abiraterone Acetate (AA) Versus Relugolix Plus AA for Advanced Prostate Cancer: The REVELUTION-2 Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 72
- 试验地点
- 4
- 主要终点
- Incidence of ambulatory systolic blood pressure (BP) > 140 or diastolic > 90 (measurement on 2 separate days)
研究概览
简要总结
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.
详细描述
PRIMARY OBJECTIVE:
I. Measure cardiovascular outcomes between combination gonadotropin releasing hormone agonist (GNRHa, i.e. leuprolide) plus abiraterone acetate (AA) versus gonadotropin releasing hormone antagonist (GNRH-antagonist, i.e. relugolix) plus AA in men with advanced prostate cancer receiving definitive radiation therapy.
SECONDARY OBJECTIVES:
I. Identify genomic alterations that predispose an individual to enhanced cardiovascular (CV) toxicity following hormone therapy with leuprolide or relugolix in combination with abiraterone acetate.
II. Evaluate serum testosterone kinetics during and after treatment with combination leuprolide+AA versus relugolix+AA.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Investigator, Outcomes Assessor)
盲法说明
All principal investigators and co-investigators will be blinded to randomization block. All cardiac computed tomography images will be analyzed by a blinded level 3 boarded cardiac imaging expert.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Men ≥ 18 years old
- •Non-metastatic prostate cancer
- •Non-metastatic, biochemically recurrent prostate cancer
- •Plan to undergo curative-intent pelvic radiation therapy (photons or protons) with or without brachytherapy
- •Plan to undergo up to 24 months of combination androgen deprivation therapy (ADT) plus AA and prednisone
排除标准
- •Metastatic prostate cancer requiring indefinitive ADT or chemotherapy
- •Prior exposure to androgen deprivation therapy
- •Prior exposure to chemotherapy, immunotherapy, or radiation therapy
- •History of cardiac bypass surgery or percutaneous coronary intervention
- •History of cardiac pacemaker or defibrillator
研究组 & 干预措施
Arm I (leuprolide plus abiraterone acetate/prednisone)
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.
干预措施: Abiraterone Acetate (Drug)
Arm I (leuprolide plus abiraterone acetate/prednisone)
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.
干预措施: Bicalutamide (Drug)
Arm I (leuprolide plus abiraterone acetate/prednisone)
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.
干预措施: Biospecimen Collection (Procedure)
Arm I (leuprolide plus abiraterone acetate/prednisone)
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.
干预措施: Computed Tomography Angiography (Procedure)
Arm I (leuprolide plus abiraterone acetate/prednisone)
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.
干预措施: Leuprolide (Drug)
Arm I (leuprolide plus abiraterone acetate/prednisone)
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.
干预措施: Prednisone (Drug)
Arm I (leuprolide plus abiraterone acetate/prednisone)
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.
干预措施: Radiation Therapy (Radiation)
Arm II (relugolix + abiraterone acetate/prednisone)
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.
干预措施: Abiraterone Acetate (Drug)
Arm II (relugolix + abiraterone acetate/prednisone)
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.
干预措施: Biospecimen Collection (Procedure)
Arm II (relugolix + abiraterone acetate/prednisone)
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.
干预措施: Computed Tomography Angiography (Procedure)
Arm II (relugolix + abiraterone acetate/prednisone)
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.
干预措施: Prednisone (Drug)
Arm II (relugolix + abiraterone acetate/prednisone)
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.
干预措施: Radiation Therapy (Radiation)
Arm II (relugolix + abiraterone acetate/prednisone)
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.
干预措施: Relugolix (Drug)
结局指标
主要结局
Incidence of ambulatory systolic blood pressure (BP) > 140 or diastolic > 90 (measurement on 2 separate days)
时间窗: At baseline and up to 12 months
The change will be estimated and tested using paired tests (Wilcoxon signed rank test or McNemar test). The difference at each interval for the two groups will be tested using Fisher's exact test for binary endpoints or Wilcoxon rank-sum test for continuous. Data transformation to fit statistical assumptions will be done as needed. Multivariable models that control for potential confounders will be implemented using general linear and logistic regression.
Need for new or escalated anti-hypertensive medication
时间窗: At baseline and up to 12 months
The change will be estimated and tested using paired tests (Wilcoxon signed rank test or McNemar test). The difference at each interval for the two groups will be tested using Fisher's exact test for binary endpoints or Wilcoxon rank-sum test for continuous. Data transformation to fit statistical assumptions will be done as needed. Multivariable models that control for potential confounders will be implemented using general linear and logistic regression.
Incidence of moderate-to-severe atherosclerosis of major coronary vessels
时间窗: From month 0 to month 12
Defined as \> 50% luminal stenosis per the Society of Cardiac Computed Tomography. Change will be tested using paired tests (Wilcoxon signed rank test or McNemar test). Luminal stenosis will be measured on a per-vessel basis. Proportion of patients achieving \> 50% luminal stenosis of a major coronary vessel between each arm will be compared using Fisher's exact test. The percent change of maximal stenosis between the two arms will be tested using Wilcoxon signed rank test.
次要结局
- Total plaque volume(From month 0 to month 12)
- Pre-existing genomic alterations promoting inflammatory immunity and associated with cardiovascular disease(At baseline)
- Castration rate(At study days 7, 30 and 90)
- Sustained castration(At months 6 and 12)
- Testosterone recovery(At day 30 and/or day 90 following completion of androgen deprivation therapy)
研究者
Sagar Patel
Principal Investigator
Emory University