Adaptive Randomization of Aerobic Exercise During Chemotherapy in Colon Cancer

结肠癌化疗期间有氧运动的适应性随机化

• 批准号: 10450944
• 负责人: Justin C Brown
• 金额: $ 118.41万
• 依托单位: LSU PENNINGTON BIOMEDICAL RESEARCH CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-03 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10450944
• 关键词: Adherence; Adverse event; Aerobic Exercise; Behavioral; Biological Markers; Biological Response Modifiers; Body Composition; Body fat; Boston; Calibration; Cancer Survivor; Caring; Cessation of life; Chemotaxis; Clinical; Clinical Practice Guideline; Colon Carcinoma; Common Terminology Criteria for Adverse Events; Complex; Counseling; Data; Disease; Dose; Dose-Limiting; Drug Kinetics; Drug or chemical Tissue Distribution; Dual-Energy X-Ray Absorptiometry; Elastases; Exercise; Fatty acid glycerol esters; Geographic Locations; Guidelines; Histone H3; Home; Immune system; Impairment; Incidence; Intervention; Malignant Neoplasms; Measures; Muscle; Neutropenia; Obesity; Participant; Patient Outcomes Assessments; Patients; Periodicity; Peripheral Nervous System Diseases; Peroxidases; Pharmaceutical Preparations; Phenotype; Physiological; Probability; Randomized; Recurrence; Reporting; Research Design; Respiratory Burst; Risk; Severities; Stretching; Supportive care; Symptoms; Techniques; Telephone; Thinness; Time; Tissues; Toxic effect; Toxicity due to chemotherapy; Translating; Variant; attentional control; behavior change; cancer care; chemotherapy; evidence base; exercise adherence; exercise physiologist; exercise prescription; exercise training; experience; gastrointestinal; heart rate monitor; immune function; improved; muscle form; neutrophil; novel; patient oriented; preservation; primary endpoint; recruit; response; sarcopenic obesity; secondary endpoint; socioeconomics; synergism; treadmill; video chat

PROJECT SUMMARY/ABSTRACT Patients with colon cancer who require chemotherapy dose reductions and treatment delays are twice as likely to experience disease recurrence and death than patients who complete their full chemotherapy dose on time. Up to 60% of patients develop toxicities of sufficient severity to require chemotherapy dose reductions or treatment delays. We hypothesize that aerobic exercise improves chemotherapy relative dose intensity and reduces patient-reported chemotherapy toxicities by improving the calibration of chemotherapy through changes in body composition and altering immune function. In response to RFA-CA-21-031, we will conduct a Bayesian, multi-stage, response-adaptive, dose-ranging trial of aerobic exercise. Participants will be 219 stage II-III colon cancer survivors recruited from three diverse socioeconomic, racial, and geographic regions (Baton Rouge, LA; Boston, MA; Oakland, CA). The first 80 participants are randomized to 1 of 5 groups equally: moderate-intensity aerobic exercise at 75 min/wk, 150 min/wk, 225 min/wk, 300 min/wk, or attention control (stretching). This is followed by adaptive randomization in which subsequent participants are assigned to an exercise group in a ratio proportional to the probability that the specific exercise group improves chemotherapy dose intensity and is feasible. Exercise is chemotherapy-periodized with more and less demanding weeks to accommodate cyclical variations in patient-reported symptoms. Aim 1 will evaluate the dose-response effects of moderate-intensity aerobic exercise compared with attention control on chemotherapy relative dose intensity (primary endpoint). Aim 2 will determine the effect of moderate-intensity aerobic exercise compared with control on gastrointestinal and peripheral neuropathy symptoms assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events [PRO-CTCAE (key secondary endpoint)]. Aim 3 will determine the effect of moderate-intensity aerobic exercise compared with control on whole-body tissue distribution (total body fat mass and lean mass) measured using dual-energy x-ray absorptiometry. Aim 4 will determine the effect of moderate-intensity aerobic exercise compared with control on changes in neutrophil counts, phenotypes, and functions (biomarkers of neutrophil effector functions including elastase, citrullinated Histone H3, and myeloperoxidase and direct measures of chemotaxis and oxidative burst). This study will leverage a transdisciplinary team's synergies to identify an exercise prescription that is patient-centered and proven to have a high probability of clinical benefit. This study will directly inform clinical practice guidelines that recognize exercise as an essential supportive care intervention for chemotherapy and establish exercise training as obligatory for delivering high-quality, evidence-based care to colon cancer survivors.

项目摘要/摘要 需要化疗剂量降低和治疗延迟的结肠癌患者的可能性是 与按时完成全部化学疗法的患者相比，经历疾病复发和死亡。 多达60％的患者患有足够严重程度的毒性需要降低化疗或 治疗延迟。我们假设有氧运动可以改善化学疗法相对剂量强度和 通过通过改善化学疗法的校准，通过通过 身体成分的变化和免疫功能改变。为了响应RFA-CA-21-031，我们将进行一次 贝叶斯，多阶段，反应自适应，有氧运动的剂量范围试验。参与者将是219阶段 II-III结肠癌幸存者从三种不同的社会经济，种族和地理区域（巴吞 洛杉矶鲁格；马萨诸塞州波士顿；加利福尼亚州奥克兰）。前80名参与者平均将5组中的1个随机分配到1组中： 75分钟/周，150分钟/周，225分钟/周，300分钟/wk或注意力控制的中等强度有氧运动或注意力控制 （拉伸）。接下来是自适应随机化，将后续参与者分配给 运动组的比例与特定运动组改善化学疗法的概率成正比 剂量强度，是可行的。锻炼是化学疗法周期性的，越来越小的几周 适应患者报告症状的周期性变化。 AIM 1将评估剂量反应效应 与对化学疗法相对剂量强度的注意力控制相比，中等强度的有氧运动 （主要终点）。 AIM 2将确定中等强度有氧运动的影响 控制使用患者报告的胃肠道和周围神经病症状的控制 不良事件的常见术语标准的结果版[Pro-CTCAE（关键次要 端点）]。 AIM 3将确定中等强度有氧运动的影响与对照 使用双能量X射线测量的全身组织分布（总体内脂肪质量和瘦质量） 吸收法。 AIM 4将确定中等强度有氧运动的影响 关于中性粒细胞计数，表型和功能的变化（中性粒细胞效应的生物标志物 包括弹性蛋白酶，瓜氨酸组蛋白H3和髓过氧化物酶以及趋化性和直接测量 氧化爆发）。这项研究将利用跨学科团队的协同作用来确定练习 处方以患者为中心，被证明具有很高的临床益处。这项研究会 直接告知临床实践指南，该指南将运动视为必不可少的支持护理干预措施 进行化学疗法并建立运动培训，以提供高质量的循证护理 为结肠癌幸存者。