Intensive Blood Pressure Control During Cardiotoxic Breast Cancer Treatment (PROTECT) Trial

心脏毒性乳腺癌治疗 (PROTECT) 试验期间强化血压控制

• 批准号: 10660289
• 负责人: Anthony Francis Yu
• 金额: $ 63.42万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10660289
• 关键词: Address; Adrenergic beta-Antagonists; Adverse event; Algorithms; Angiotensin-Converting Enzyme Inhibitors; Anthracycline; Attenuated; Biological Markers; Blood Pressure; Breast Cancer Treatment; Breast Cancer survivor; Breast Cancer therapy; CXCL10 gene; Cardiac Myocytes; Cardiotoxicity; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cessation of life; Clinical; Cyclic GMP; Data; Development; Epidermal Growth Factor Receptor; Event; Exclusion; Frequencies; Future; Goals; Guidelines; Heart failure; Human; Hypertension; Image; Impairment; Inflammation; Intervention; Investigation; Knowledge; Left Ventricular Ejection Fraction; Long-Term Survivors; Malignant Neoplasms; Measures; Modeling; Morbidity - disease rate; Myocarditis; Natriuretic Peptides; Oncology; Outcome; Oxygen Consumption; Patient Outcomes Assessments; Patients; Play; Prevention; Prognostic Marker; Quality of life; Random Allocation; Randomized, Controlled Trials; Recommendation; Risk; Risk Factors; Role; Safety; Stimulator of Interferon Genes; Stress; Stroke; Toxic effect; Troponin; Woman; Work; blood pressure control; cancer care; cancer initiation; cancer therapy; cardioprotection; cardiorespiratory fitness; cardiovascular health; cardiovascular risk factor; cell free DNA; chemotherapy; circulating biomarkers; clinical implementation; clinically significant; comorbidity; efficacy evaluation; high risk; hypertension control; hypertension treatment; improved; insight; malignant breast neoplasm; modifiable risk; mortality; myocardial injury; prevent; primary outcome; randomized trial; secondary outcome; standard care; targeted agent; targeted treatment; therapy development; treatment response; treatment trial; trial design

PROJECT SUMMARY Hypertension (HTN) is the most common cardiovascular (CV) comorbidity among patients with breast cancer and is an important modifiable risk factor for adverse CV events during and after cancer treatment. Work by our group and others has shown that HTN is an important risk factor for cardiotoxicity caused by curative breast cancer treatments including anthracyclines and human epidermal growth factor receptor 2 (HER2) targeted agents, which occurs in up to 20% of patients receiving these therapies and presents with a reduced left ventricular ejection fraction or heart failure. Furthermore, cardiotoxicity is a leading treatment-limiting toxicity that interferes with curative cancer treatment delivery, worsens cancer outcomes, and leads to persistent impairment of cardiorespiratory fitness in long-term survivors of breast cancer. CV disease is now a leading cause of morbidity and mortality among breast cancer survivors who are living longer due to advances in cancer care, therefore strategies to mitigate CV risk in patients with breast cancer are critically needed. No standard treatment option is currently available to prevent cardiotoxicity during cancer treatment, and no guidelines exist to inform the optimal approach to blood pressure control during cancer treatment. Multiple trials have shown that intensive blood pressure control is associated with CV risk reductions, however exclusion of patients with cancer represents an important limitation of these trials. The association between HTN and cardiotoxicity risk provide a strong rationale for optimizing blood pressure control to improve CV health and reduce cardiotoxicity risk in patients with HTN who are most vulnerable, however no previous trial has assessed the role of intensive blood pressure control on the cardiotoxic effects of breast cancer treatment. The objective of this study is therefore to evaluate intensive systolic blood pressure (SBP) control in women with HTN at risk for cardiotoxicity during BC treatment and the effects of intensive SBP control on biomarkers (imaging, functional, and circulating) of cardiotoxicity. Using a randomized controlled trial design, 130 patients with breast cancer at increased risk for cardiotoxicity (defined by baseline SBP ≥130 mm Hg and treatment with anthracyclines with or without HER2- targeted therapy) will be randomly allocated (ratio 1:1) to intensive SBP control (goal SBP <120 mm Hg) versus standard SBP control (goal SBP <140 mm Hg) prior to initiating breast cancer treatment. Aim 1: Evaluate the efficacy of an intensive SBP control intervention during active BC treatment in patients at risk for cardiotoxicity. Aim 2: Evaluate the effects of intensive SBP control on imaging and functional biomarkers of cardiotoxicity. Aim 3: Assess the effect of intensive SBP control on circulating biomarkers of cardiotoxicity. The results from this investigation will: 1) establish critical data to inform clinical implementation of intensive SBP control for patients with breast cancer at risk for cardiotoxicity, 2) provide functional and mechanistic insights into the effects of intensive SBP control on mitigation of cardiotoxicity risk, and 3) guide future cardio-oncology practice recommendations on the role of HTN management to improve CV health in patients with cancer.

项目摘要 高血压（HTN）是乳腺癌患者中最常见的心血管（CV）合并症 并且是癌症治疗期间和之后的不良简历事件的重要可修改风险因素。我们的工作 小组和其他人表明，HTN是治愈乳房引起的心脏毒性的重要危险因素 癌症治疗包括蒽环类药物和人类表皮生长因子受体2（HER2）针对的 代理，最多20％接受这些疗法的患者和左侧的疗法均减少 心室射血分数或心力衰竭。此外，心脏毒性是一种领先的治疗限制性毒性 干扰治愈性癌症治疗的递送，恶化癌症的结果并导致持续的损害 乳腺癌长期存活中心肺适应性的。 CV病现在是 由于癌症护理的进步，乳腺癌生存的发病率和死亡率更长， 因此，至关重要的是乳腺癌患者减轻简历风险的策略。没有标准治疗 目前可以选择可预防癌症治疗期间心脏毒性的选择，并且不存在指南来告知心脏毒性。 癌症治疗期间血压控制的最佳方法。多次试验表明密集型 血压控制与降低CV风险有关，但是排除癌症患者 代表了这些试验的重要局限性。 HTN和心脏毒性风险之间的关联提供了 优化血压控制以改善简历健康并降低心脏毒性风险的强大理由 最脆弱的HTN患者，但是以前没有试验评估了强化血液的作用 压力控制乳腺癌治疗的心脏毒性作用。因此，这项研究的目的是 在BC期间评估HTN患有心脏毒性风险的女性的强化收缩压（SBP）控制 治疗以及密集型SBP控制对生物标志物（成像，功能和循环）的影响 心脏毒性。使用随机对照试验设计，有130例乳腺癌患者的风险增加 心脏毒性（由基线SBP≥130mm Hg定义，并用具有或没有HER2-的蒽环类药物治疗 目标疗法将随机分配（比率1：1）与密集的SBP对照（目标SBP <120 mm Hg）相对于 在开始乳腺癌治疗之前，标准的SBP控制（目标SBP <140 mM Hg）。目标1：评估 在主动BC治疗期间，强化SBP控制干预措施的功效对有心脏毒性风险的患者。 AIM 2：评估密集型SBP控制对成像和心脏毒性功能生物标志物的影响。目的 3：评估密集型SBP控制对心脏毒性循环生物标志物的影响。从中的结果 调查将：1）建立关键数据，以告知患者强化SBP控制的临床实施 乳腺癌有患心脏毒性的风险，2）提供功能和机械洞察力，以了解 强化SBP控制缓解心脏毒性风险，3）指导未来的心脏肿瘤实践 关于HTN管理在改善癌症患者CV健康方面作用的建议。