Mechanism and Predictors of Cardiotoxicity After Prostate Cancer Treatment: A Parallel Cohort and Randomized Trial Comparing Radiation Alone, Radiation Plus Leuprolide, and Radiation Plus Relugolix
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 94
- 试验地点
- 4
- 主要终点
- Total Coronary Plaque Volume in Major Coronary Arteries (i.e. Left Anterior Descending, Left Circumflex, Right Major Coronary Arteries)
研究概览
简要总结
This clinical trial investigates the impact of prostate cancer treatment, specifically androgen deprivation therapy (ADT), on the heart and coronary vessels among men with localized, non-metastatic prostate cancer undergoing definitive radiation therapy and concomitant ADT. Recently, cardiovascular toxicity from hormone therapy that is routinely used for prostate cancer (e.g. leuprolide) has emerged as a concern, yet studies identifying who is at risk and the mechanism of cardiac damage are lacking. Additionally, a new hormone therapy drug, relugolix, has recently been Food and Drug Administration (FDA)-approved and may reduce toxicity to the heart. This trial intends to investigate the mechanism of cardiovascular toxicity from ADT, investigate the mechanism by which relugolix reduces cardiovascular toxicity, and identify predictive biomarkers to improve individualized risk-assessment for cardiovascular toxicity from ADT.
详细描述
PRIMARY OBJECTIVES:
I. Identify and compare the association of gonadotrophin releasing hormone (GNRH)-agonist leuprolide versus GNRH-antagonist relugolix with coronary atherosclerosis and progression in men with prostate cancer.
II. Determine the relationship between leuprolide versus relugolix with downstream immune effector response that is implicated in atherosclerosis.
II. Determine how pre-existing genomic alterations associated with proinflammatory immunity impact development of CV toxicity following GNRH-agonist (GNRHa) versus relugolix.
III. Identify imaging biomarkers associated with increased risk of CV toxicity from ADT
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
- Single (Outcomes Assessor)
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 with or without ADT
排除标准
- •Metastatic prostate cancer requiring > 24 months of ADT
- •Prior exposure to androgen deprivation therapy
- •Prior exposure to chemotherapy or immunotherapy
- •History of cardiac bypass surgery or percutaneous coronary intervention
研究组 & 干预措施
Arm I (radiation therapy alone)
Patients undergo definitive radiation therapy alone (IMRT, SBRT, proton therapy, brachytherapy) in the absence of disease progression or unacceptable toxicity.
干预措施: Radiation therapy (Radiation)
Arm II (radiation therapy plus leuprolide)
Patients undergo radiation therapy as in Arm I and receive leuprolide SC or IM every 3 or 6 months. Treatment continues for 6 to 12 months (depending on risk) in the absence of disease progression or unacceptable toxicity.
干预措施: Radiation therapy (Radiation)
Arm II (radiation therapy plus leuprolide)
Patients undergo radiation therapy as in Arm I and receive leuprolide SC or IM every 3 or 6 months. Treatment continues for 6 to 12 months (depending on risk) in the absence of disease progression or unacceptable toxicity.
干预措施: Leuprolide (Drug)
Arm III (radiation therapy plus relugolix)
Patients undergo radiation therapy as in Arm I and receive relugolix PO QD. Treatment continues for 6 to 12 months (depending on risk) in the absence of disease progression or unacceptable toxicity.
干预措施: Radiation therapy (Radiation)
Arm III (radiation therapy plus relugolix)
Patients undergo radiation therapy as in Arm I and receive relugolix PO QD. Treatment continues for 6 to 12 months (depending on risk) in the absence of disease progression or unacceptable toxicity.
干预措施: Relugolix (Drug)
结局指标
主要结局
Total Coronary Plaque Volume in Major Coronary Arteries (i.e. Left Anterior Descending, Left Circumflex, Right Major Coronary Arteries)
时间窗: From baseline to 12 months post-treatment initiation
Using cardiac computed tomography angiography (CCTA), total coronary plaque volume will be determined using an artificial intelligence-enabled quantitative coronary plaque analysis (AI-QCPA) through a commercially available and validated software service (HeartFlow, Inc). Each coronary artery (right coronary, left main, left anterior descending, and left circumflex) will be scored, and plaque volumes were summed over all segments.
次要结局
- Non-calcified Coronary Plaque Volume in Major Coronary Arteries (i.e. Left Anterior Descending, Left Circumflex, Right Major Coronary Arteries)(From baseline to 12 months post-treatment initiation)
研究者
Sagar Patel
Principal Investigator
Emory University