Flexible versus Standard Aerobic Training Dosing in Primary Breast Cancer: A Randomized and Response-Adapted Trial

原发性乳腺癌的灵活与标准有氧训练剂量：一项随机且适应反应的试验

基本信息

批准号：
10502148
负责人：
Jessica Scott
金额：
$ 73.45万
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：
2022-09-21 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10502148
关键词：
Address Adherence Adverse event Aerobic Aerobic Exercise Attenuated Biometry Breast Cancer Patient Breast Oncology Cancer Etiology Cardiopulmonary Clinical Common Terminology Criteria for Adverse Events Data Dose Ensure Exercise Exercise Test Exercise Therapy Frequencies Impairment Individual Investigation Knowledge Maintenance Malignant Neoplasms Memorial Sloan-Kettering Cancer Center Morbidity - disease rate Newly Diagnosed Oncology Oxygen Consumption Patient Outcomes Assessments Patient Schedules Patients Pharmaceutical Preparations Phase Population Qualifying Randomized Recovery Regimen Research Research Personnel Risk Safety Schedule Severities Structure Symptoms Testing Training Translations Treatment Efficacy Walking Work attenuation base cancer care cancer therapy cardiorespiratory fitness chemotherapy clinical care clinical implementation design digital exercise intensity flexibility improved instrument malignant breast neoplasm mortality multidisciplinary patient oriented primary endpoint randomized trial response safety outcomes secondary endpoint translational potential treadmill treatment adherence treatment as usual trial comparing

项目摘要

PROJECT SUMMARY/ABSTRACT Chemotherapy for primary breast cancer causes significant declines in cardiorespiratory fitness (CRF) predisposing patients to increased symptom burden and increased risk of morbidity and mortality from cancer and non-cancer conditions. Randomized trials demonstrate aerobic training (AT) is feasible during chemotherapy for primary breast cancer and attenuates treatment-induced impairments in CRF. However, our recent findings indicate that even with AT during and after chemotherapy, CRF remains substantially below normative values, and less than 25% of patients have a clinically meaningful CRF response. Increasing the dose of AT substantially increases CRF response; however, higher AT doses are associated with lower AT adherence. Thus, use of a conventional dose-response design wherein patients are assigned to fixed doses is likely imprudent considering lower fixed AT doses will result in underdosing in some patients, and poor adherence in others. A more patient- centered approach used in drug trials is flexible dosing, where the dose is escalated for each patient as tolerated. There have been no trials directly assessing the efficacy of flexible AT dosing on CRF in any cancer setting. To address this fundamental knowledge gap in exercise-oncology research, the objective of this study is to compare the effects of flexible versus standard fixed AT dosing and response-adapted AT on CRF response. In this randomized trial, a total of 140 inactive (<90 mins of moderate-intensity exercise/wk) patients with primary breast cancer scheduled to initiate chemotherapy will be randomly allocated (1:1) to Flexible dosing: Individual AT doses escalated; or Standard fixed dosing: 90 mins/week for ~32 weeks (during and after chemotherapy). Patients who do not respond (<3.50 ml/kg/min CRF improvement) at 32 weeks will complete 20 weeks of extended flexible dosing AT. We will address 3 specific aims: AIM 1: Compare the effects of flexible versus standard dosing on CRF response rate. AIM 2: Ascertain the effects on adherence, safety, and patient-reported outcomes. AIM 3: Evaluate the effects of extended AT in CRF non-responders. IMPACT: This study challenges the current dogma that all patients respond equally to a fixed AT dose and will be the first to evaluate flexible AT dosing in any cancer population. Receiving cancer treatment is not a qualifying condition for structured AT and, as such, AT is not currently considered a standard aspect of cancer management. We anticipate the proposed trial will directly address an unmet clinical need by identifying the AT regimen that maximizes CRF response rate and, if successful, findings from this investigation will help guide the AT regimen for translation to clinical care.

项目概要/摘要原发性乳腺癌化疗导致心肺健康 (CRF) 显着下降使患者容易增加症状负担并增加癌症发病率和死亡率的风险和非癌症状况。随机试验证明化疗期间有氧训练 (AT) 是可行的治疗原发性乳腺癌并减轻治疗引起的 CRF 损伤。然而，我们最近的发现表明即使在化疗期间和化疗后使用 AT，CRF 仍然大大低于正常值，不到 25% 的患者出现有临床意义的 CRF 反应。大幅增加AT剂量增加 CRF 反应；然而，较高的 AT 剂量与较低的 AT 依从性相关。因此，使用一个考虑到患者被分配固定剂量的传统剂量反应设计可能是不谨慎的较低的固定 AT 剂量会导致某些患者剂量不足，而另一些患者则依从性较差。更有耐心—— 药物试验中使用的中心方法是灵活剂量，根据每位患者的耐受情况逐步增加剂量。目前还没有直接评估灵活 AT 剂量在任何癌症环境中对 CRF 的疗效的试验。到为了解决运动肿瘤学研究中的这一基本知识差距，本研究的目的是比较灵活与标准固定 AT 剂量和响应适应 AT 对 CRF 响应的影响。在在这项随机试验中，共有 140 名不活动（每周中等强度运动 <90 分钟）的原发性运动障碍患者计划开始化疗的乳腺癌将被随机分配（1:1）到灵活剂量：个体 AT 剂量逐渐增加；或标准固定剂量：每周 90 分钟，持续约 32 周（化疗期间和化疗后）。 32 周时无反应（CRF 改善<3.50 ml/kg/min）的患者将完成 20 周的治疗延长灵活剂量 AT。我们将实现 3 个具体目标：目标 1：比较灵活与灵活的效果 CRF 反应率的标准剂量。目标 2：确定对依从性、安全性和患者报告的影响结果。目标 3：评估延长 AT 对 CRF 无应答者的影响。影响：这项研究挑战当前的教条是所有患者对固定 AT 剂量的反应相同，并且将是第一个评估灵活 AT 的人任何癌症人群的剂量。接受癌症治疗不是结构化 AT 的资格条件，并且，因此，AT 目前不被视为癌症管理的标准方面。我们预计拟议的试验将通过确定最大化 CRF 缓解率的 AT 方案来直接解决未满足的临床需求如果成功，这项调查的结果将有助于指导 AT 方案转化为临床护理。