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: 10708044
• 负责人: Jessica Scott
• 金额: $ 70.86万
• 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/10708044
• 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; 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; Quality of life; Random Allocation; Randomized; Recovery; Regimen; Research; Research Personnel; Risk; Safety; Schedule; Severities; Structure; Symptoms; Testing; Translations; Treatment Efficacy; Walking; Work; attenuation; cancer care; cancer initiation; cancer therapy; cardiorespiratory fitness; chemotherapy; clinical care; clinical implementation; conventional dosing; design; digital; efficacy evaluation; exercise intensity; flexibility; improved; instrument; malignant breast neoplasm; mortality; multidisciplinary; patient oriented; primary endpoint; randomized trial; response; 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.

项目摘要/摘要 原发性乳腺癌的化学疗法会导致心肺健康（CRF）大幅下降 使患者易于增加症状负担，并增加了癌症发病率和死亡率的风险 和非癌症条件。随机试验表明有氧训练（AT）是在化学疗法期间可行的 用于原发性乳腺癌并减弱治疗引起的CRF损伤。但是，我们最近的发现 表明即使在化学疗法期间和之后，CRF仍然大大低于规范值， 不到25％的患者具有临床意义的CRF反应。大大增加剂量 增加CRF响应；但是，剂量的较高与依从性较低有关。因此，使用 常规剂量反应设计，其中将患者分配给固定剂量可能是不明智的 剂量下的固定剂量将导致某些患者的服用不足，而其他患者的依从性较差。一个更患者 - 药物试验中使用的中心方法是柔性给药的，在该剂量下，每位患者的剂量被耐受。 在任何癌症环境中，尚无试验直接评估柔韧性在CRF的疗效。到 解决了运动肿瘤研究中的这个基本知识差距，这项研究的目的是 比较固定在给药时固定的柔性与标准的效果，并适应了对CRF响应的响应。在 这项随机试验，总共140个非活性（<90分钟的中等强度运动/周） 计划启动化学疗法的乳腺癌将随机分配（1：1）以柔性剂量：个人 以剂量升级；或标准固定剂量：90分钟/周，持续32周（化学疗法期间和之后）。 在32周时不反应的患者（改善3.50 mL/kg/min CRF）将完成20周 扩展柔性给药。我们将解决3个具体目标：目标1：比较灵活的效果 CRF响应率的标准剂量。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：评估在CRF非反应器中扩展的影响。影响：这项研究挑战 当前所有患者对剂量固定的剂量的反应均等，并将是第一个评估灵活的教条 在任何癌症人群中给药。接受癌症治疗并不是结构化的合格条件和 因此，目前尚未将其视为癌症管理的标准方面。我们期待提议的 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 而且，如果成功的话，这项调查的结果将有助于指导AT方案转化为临床护理。