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.

项目总结