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

• 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
• 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

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.

项目总结/摘要 原发性乳腺癌的化疗导致心肺适应性（CRF）显著下降 使患者易于增加癌症的症状负担和发病率和死亡率风险 和非癌症条件。随机试验表明，有氧训练（AT）在化疗期间是可行的 治疗原发性乳腺癌，并减轻治疗引起的CRF损害。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仍显著低于正常值， 不到25%的患者有临床意义的CRF反应。大幅度增加AT的剂量 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A 传统的剂量反应设计，其中患者被分配到固定剂量可能是轻率的，考虑到 较低的固定AT剂量将导致某些患者的剂量不足，以及其他患者的依从性差。更有耐心- 在药物试验中使用的集中方法是灵活的剂量，其中剂量根据每个患者的耐受性逐步增加。 目前还没有试验直接评估在任何癌症背景下灵活AT给药对CRF的疗效。到 为了解决运动肿瘤学研究中的这一基本知识缺口，本研究的目的是 比较灵活与标准固定AT给药和反应适应性AT对CRF反应的影响。在 这项随机试验，共有140名非活动（<90分钟的中等强度运动/周）的原发性高血压患者， 计划开始化疗的乳腺癌患者将随机（1：1）分配至灵活给药组：个体 AT剂量递增;或标准固定剂量：90分钟/周，持续约32周（化疗期间和化疗后）。 在第32周时没有反应（CRF改善<3.50 ml/kg/min）的患者将完成20周的治疗。 扩展灵活的剂量AT。我们将讨论3个具体目标：目标1：比较灵活与 标准剂量对CRF应答率的影响。目的2：确定对依从性、安全性和患者报告的影响 结果。目的3：评价延长AT在CRF无应答者中的作用。影响：这项研究挑战 目前的教条是所有患者对固定AT剂量的反应相同，并将首先评估灵活的AT 任何癌症人群中的剂量。接受癌症治疗不是结构性AT的合格条件， 因此，AT目前不被认为是癌症治疗的标准方面。我们预计， 试验将通过确定最大化CRF应答率的AT方案，直接解决未满足的临床需求 如果成功的话，这项研究的结果将有助于指导AT方案转化为临床护理。