REVELUTION-2: Relugolix+Abiraterone Acetate (AA) Versus Leuprolide+AA Cardiac Trial

Официальное название

Randomized Controlled Trial of Leuprolide Plus Abiraterone Acetate (AA) Versus Relugolix Plus AA for Advanced Prostate Cancer: The REVELUTION-2 Trial

Обзор

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.

Подробное описание

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.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive leuprolide intramuscularly (IM) or subcutaneously (SC) injection every 3 to 6 months plus oral 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. Patients may also receive bicalutamide orally (PO) once daily (QD) on days 21-30 with first injection of leuprolide at the discretion of the treating provider. All patients undergo pre-treatment and 12-month coronary computed tomography angiography (CCTA) and blood sample collection.

ARM II: Patients receive oral relugolix PO daily plus oral 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. All patients undergo pre-treatment and 12-month CCTA and blood sample collection.

After completion of study treatment, patients are followed up at 30 and 60 days for serum testosterone measurement.

Вмешательства

• Препарат Abiraterone Acetate
  Given abiraterone acetate
• Препарат Bicalutamide
  Given PO
• Процедура Biospecimen Collection
  Undergo blood sample collection
• Процедура Computed Tomography Angiography
  Undergo CCTA
• Препарат Leuprolide
  Given IM or SC
• Препарат Prednisone
  Given prednisone
• Лучевая терапия Radiation Therapy
  Undergo standard of care radiation therapy
• Препарат Relugolix
  Given PO

Первичные конечные точки

• Incidence of ambulatory systolic blood pressure (BP) > 140 or diastolic > 90 (measurement on 2 separate days) [Срок оценки: At baseline and up to 12 months]
• Need for new or escalated anti-hypertensive medication [Срок оценки: At baseline and up to 12 months]
• Incidence of moderate-to-severe atherosclerosis of major coronary vessels [Срок оценки: From month 0 to month 12]

Вторичные конечные точки (5)

• Total plaque volume [Срок оценки: From month 0 to month 12]
• Pre-existing genomic alterations promoting inflammatory immunity and associated with cardiovascular disease [Срок оценки: At baseline]
• Castration rate [Срок оценки: At study days 7, 30 and 90]
• Sustained castration [Срок оценки: At months 6 and 12]
• Testosterone recovery [Срок оценки: At day 30 and/or day 90 following completion of androgen deprivation therapy]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 4 центра

• Emory Proton Therapy Center — Atlanta
• Winship at Emory Midtown — Atlanta
• Emory University Hospital/Winship Cancer Institute — Atlanta
• Emory Saint Joseph's Hospital — Atlanta

Идентификаторы

NCT: NCT06650579 · STUDY00007557 · P30CA138292 · NCI-2024-07761 · STUDY00007557 · RAD6197-24

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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