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.

项目概要/摘要 需要减少化疗剂量和延迟治疗的结肠癌患者的可能性是其两倍 与按时完成全部化疗剂量的患者相比，经历疾病复发和死亡的患者。 高达 60% 的患者出现足够严重的毒性，需要减少化疗剂量或 治疗延误。我们假设有氧运动可以改善化疗的相对剂量强度，并且 通过改善化疗的校准来减少患者报告的化疗毒性 身体成分的变化和免疫功能的改变。为了响应 RFA-CA-21-031，我们将进行一次 有氧运动的贝叶斯、多阶段、反应适应性、剂量范围试验。参赛者将有219个舞台 从三个不同的社会经济、种族和地理区域招募的 II-III 结肠癌幸存者（Baton 路易斯安那州鲁日；马萨诸塞州波士顿；加利福尼亚州奥克兰）。前 80 名参与者被随机分配到 5 组中的一组： 每周 75 分钟、150 分钟、225 分钟、300 分钟的中等强度有氧运动，或注意力控制 （伸展）。接下来是自适应随机化，其中后续参与者被分配到一个 运动组的比例与特定运动组改善化疗的概率成正比 剂量强度是可行的。运动是按照化疗周期进行的，有或多或少的要求周数 适应患者报告症状的周期性变化。目标 1 将评估剂量反应效应 中等强度有氧运动与注意力控制对化疗相对剂量强度的影响 （主要终点）。目标 2 将确定中等强度有氧运动与有氧运动相比的效果 使用患者报告评估的胃肠道和周围神经病变症状的控制 不良事件通用术语标准的结果版本 [PRO-CTCAE（关键次要 终点）]。目标 3 将确定中等强度有氧运动与对照组相比的效果 使用双能 X 射线测量全身组织分布（全身脂肪量和瘦肉量） 吸收测定法。目标 4 将确定中等强度有氧运动与对照相比的效果 中性粒细胞计数、表型和功能的变化（中性粒细胞效应功能的生物标志物 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 氧化爆发）。这项研究将利用跨学科团队的协同作用来确定一项练习 以患者为中心并被证明具有较高临床获益可能性的处方。这项研究将 直接告知临床实践指南，将运动视为基本的支持性护理干预措施 化疗并建立运动训练作为提供高质量、循证护理的强制性要求 结肠癌幸存者。