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.

项目总结/摘要 结肠癌患者需要减少化疗剂量和治疗延迟的可能性是两倍 比按时完成全部化疗剂量的患者更容易发生疾病复发和死亡。 高达60%的患者出现严重程度足以要求化疗剂量降低的毒性，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， 通过改善化疗校准，降低患者报告的化疗毒性， 改变身体组成和改变免疫功能。根据RFA-CA-21-031，我们将进行 有氧运动的贝叶斯、多阶段、反应适应性、剂量范围试验。参加者将在219阶段 II-III结肠癌幸存者从三个不同的社会经济、种族和地理区域招募（Baton Rouge，LA; Boston，MA; Oakland，CA）。前80名参与者被随机分为5组： 中等强度有氧运动，75 min/wk、150 min/wk、225 min/wk、300 min/wk或注意力控制 （拉伸）。随后是自适应随机化，其中后续参与者被分配到 运动组的比例与特定运动组改善化疗的概率成正比 剂量强度和可行性。锻炼是化疗周期性的，要求周数或多或少， 适应患者报告症状的周期性变化。目的1将评价剂量反应效应 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 使用患者报告量表评估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局版本[PRO-CTCAE（关键次要 端点）]。目的3将确定与对照组相比，中等强度有氧运动对 使用双能X射线测量全身组织分布（全身脂肪量和瘦体重） 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（中性粒细胞效应子功能的生物标志物）的变化 包括弹性蛋白酶、瓜氨酸化组蛋白H3和髓过氧化物酶以及趋化性的直接测量， 氧化爆发）。本研究将利用跨学科团队的协同作用， 以患者为中心并被证明具有很高的临床获益可能性的处方。本研究将 直接告知临床实践指南，该指南将运动视为必要的支持性护理干预 并将运动训练作为提供高质量循证护理的必要条件 给结肠癌幸存者