Dose-response of aerobic training during total neoadjuvant therapy for locally advanced rectal cancer

局部晚期直肠癌新辅助治疗期间有氧训练的剂量反应

基本信息

批准号：
10451201
负责人：
Andrea Cercek
金额：
$ 128.43万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-06 至 2027-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10451201
关键词：
Address Adherence Aerobic Age Anemia Antiemetics Apoptosis Attenuated Behavior Therapy Biological Biological Assay Blinded Cancer Control Cancer Patient Case Report Form Cell Differentiation process Cessation of life Clinical Clinical Research Common Terminology Criteria for Adverse Events Complete Blood Count Correlative Study Data Diagnosis Disease-Free Survival Dose Erythrocytes Evaluation Event Exercise Exercise Therapy F2-Isoprostanes Fatigue Female Flow Cytometry Generations Guidelines Hematology Hematopoietic stem cells Hemoglobin Home Impairment In complete remission Incidence Investigation Knowledge Malignant Neoplasms Mass Spectrum Analysis Modeling Modification Neoadjuvant Therapy Neutropenia Oncologist Oncology Operative Surgical Procedures Outcome Pathologic Patient Education Patient Outcomes Assessments Patient Schedules Patients Pharmaceutical Preparations Pharmacotherapy Phase Phase II/III Trial Physiological Pilot Projects Postoperative Complications Protocols documentation Qualifying Quality of life Reactive Oxygen Species Recovery Rectal Cancer Regimen Reporting Research Risk Safety Sample Size Schedule Site Standardization Structure Survival Rate Techniques Testing Time Toxic effect Training Translating Treatment-related toxicity Walking Work adjudicate cancer care cancer diagnosis cancer survival cancer therapy cancer type chemoradiation chemotherapy clinical practice design digital evidence base exercise intensity improved male malignant breast neoplasm meetings neutrophil patient population point of care preclinical study primary endpoint psychosocial randomized trial real time monitoring response sex standard of care treadmill treatment planning tumor

项目摘要

PROJECT SUMMARY/ABSTRACT Randomized trials demonstrate aerobic training (AT) attenuates treatment-induced impairments in physiological and psychosocial outcomes in a broad number of cancer patient populations. However, whether AT specifically impacts the tolerability of cancer treatment is largely unknown. To address this fundamental knowledge gap in exercise-oncology research, the objective of this study is to evaluate the dose-response of AT on treatment tolerability and related outcomes in patients with locally advanced rectal cancer (LARC) initiating total neoadjuvant therapy (TNT). LARC is an ideal model in which to conduct a definitive trial of AT on treatment tolerability for several reasons: (1) high rate of LARC diagnoses annually in the U.S. (>40,000), (2) poor tolerability of TNT (<60% of patients complete the recommended regimen), and (3) strong biological rationale (TNT-induced impairment in hematological function is the major cause of poor tolerability, and AT is demonstrated to enhance hematological function in preclinical and clinical studies). Therefore, in this phase 2 randomized trial, a total of 225 inactive (<60 mins of moderate-intensity exercise/wk) patients with LARC scheduled to initiate TNT will be stratified by sex (male vs. females) and age (<55 years vs. >55 years) and randomly allocated (1:1:1 ratio) to receive: 90 mins/week, 150 mins/week, or 300 mins/week from pre-treatment to pre-surgery (~32 weeks). All AT dose regimens will be prescribed according to standard AT principles and implemented using our digital AT platform permitting all sessions to be performed in patients’ homes with remote real-time monitoring. We will address 3 specific aims: AIM 1: Determine dose-response of AT on TNT treatment tolerability. AIM 2: Evaluate AT dose-response on hematological function. AIM 3: Explore AT dose-response on tumor clinical outcomes. The proposed study directly addresses an unmet clinical need by testing, for the first time, the dose-response effects of AT on multiple treatment-related outcomes in patients with LARC receiving TNT. The proposed study will improve behavioral intervention protocols for patients undergoing cancer treatment by using our digital exercise approach that expands access to AT for patients not residing within close proximity of a research site. Receiving cancer treatment is not a qualifying condition for exercise therapy and, as such, exercise is not currently considered a standard aspect of cancer management. Therefore, if successful, findings from this investigation will also shift clinical paradigms regarding exercise therapy in cancer by adding to a growing body of evidence supporting integration of AT into standard clinical cancer care.

项目概要/摘要随机试验表明有氧训练 (AT) 可减轻治疗引起的生理损伤然而，无论是 AT 特异，还是广大癌症患者群体的心理社会结果。癌症治疗的耐受性的影响在很大程度上尚不清楚。运动肿瘤学研究，本研究的目的是评估 AT 对治疗的剂量反应局部晚期直肠癌 (LARC) 患者的耐受性和相关结果新辅助治疗 (TNT) 是进行 AT 治疗明确试验的理想模型。耐受性有几个原因：(1) 美国每年 LARC 诊断率很高（>40,000），(2) 较差 TNT 的耐受性（<60% 的患者完成了推荐的治疗方案），以及 (3) 强有力的生物学原理（TNT引起的血液功能损害是耐受性差的主要原因，而AT是在临床前和临床研究中证明可以增强血液学功能）因此，在本阶段 2 中。随机试验，总共 225 名不活动（每周中等强度运动 <60 分钟）的 LARC 患者计划启动 TNT 将按性别（男性与女性）和年龄（<55 岁与>55 岁）进行分层，随机分配（1:1:1 比例）接受：治疗前 90 分钟/周、150 分钟/周或 300 分钟/周至手术前（约 32 周）。所有 AT 剂量方案将根据标准 AT 原则和规定制定。使用我们的数字 AT 平台实施，允许所有会议在患者家中进行远程我们将实现 3 个具体目标：目标 1：确定 AT 对 TNT 治疗的剂量反应。目标 2：评估 AT 对血液学功能的剂量反应。 AIM 3：探索 AT 对血液学功能的剂量反应。拟议的研究首次通过测试直接解决了未满足的临床需求。在接受 LARC 治疗的患者中，AT 对多种治疗相关结局的剂量反应效应 TNT。拟议的研究将改善接受癌症治疗的患者的行为干预方案。通过使用我们的数字锻炼方法，为居住在附近的患者扩大 AT 的使用范围接受癌症治疗不是运动疗法的合格条件，因此，目前，运动不被认为是癌症治疗的标准方面，因此，如果成功的话，研究结果会有所不同。这项研究还将改变癌症运动疗法的临床范式越来越多的证据支持将 AT 纳入标准临床癌症护理。