Randomized Phase II Trial of Prolonged Overnight Fasting and/or Exercise on Fatigue and Other Patient Reported Outcomes in Women with Hormone Receptor Positive Advanced Breast Cancer (FastER)

长期隔夜禁食和/或运动对激素受体阳性晚期乳腺癌女性患者疲劳和其他患者报告结果的随机 II 期试验 (FastER)

• 批准号: 10714371
• 负责人: Tracy E Crane
• 金额: $ 81.06万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-20 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10714371
• 关键词: Address; Advanced Malignant Neoplasm; Adverse effects; Anxiety; Aromatase Inhibitors; Attenuated; Biological Markers; Body Composition; C-reactive protein; CDK4 gene; Carbohydrates; Chemotherapy and/or radiation; Circadian Rhythms; Cyclin-Dependent Kinase Inhibitor; Data; Development; Diet; Dietary Intervention; Dose; Eating; Effectiveness; Enrollment; Evaluation; Exercise; Fasting; Fatigue; Fulvestrant; Goals; Hormone Receptor; Hour; Individual; Inflammation; Inflammatory; Interleukin-6; Intermittent fasting; Intervention; Life; Mediating; Menopausal Symptom; Mental Depression; Metastatic breast cancer; Minority Groups; Mood Disorders; Neutropenia; Outcome; Outcome Study; Participant; Patient Outcomes Assessments; Patients; Pharmaceutical Preparations; Phase; Physical Function; Physical activity; Physical assessment; Pilot Projects; Population; Quality of life; Randomized; Randomized, Controlled Trials; Reporting; Research; Risk; Sampling; Sleep; Sleep disturbances; TNF gene; Testing; Toxic effect; Treatment Side Effects; Treatment-related toxicity; Underrepresented Minority; Well in self; Woman; acceptability and feasibility; advanced breast cancer; advanced disease; adverse outcome; attentional control; cancer initiation; cancer therapy; chemotherapy; circadian; diet and exercise; ethnic diversity; exercise intensity; exercise intervention; exercise training; experience; feasibility testing; gastrointestinal; hormone receptor-positive; hormone therapy; improved; improved outcome; improvement on sleep; inflammatory marker; inhibitor; inhibitor therapy; intervention effect; lifestyle intervention; malignant breast neoplasm; novel; patient population; phase II trial; post intervention; preservation; primary outcome; psychologic; secondary outcome; side effect; targeted treatment; tumor

Abstract More than 40,000 women die each year of metastatic breast cancer. The majority of these tumors are hormone receptor positive (HR+) that are treated with a cyclin dependent kinase 4/6 (CDK4/6) inhibitor in combination with an aromatase inhibitor or fulvestrant. With these treatments, women with advanced breast cancer are living longer, but treatment related toxicities inevitably occur, and quality of life is limited by side effects of cancer treatment which may result in dose reductions and delays. Fatigue is the most commonly cited adverse side effect reported for women taking CDK4/6 inhibitors and mechanistically may be associated with inflammation. When unmanaged, fatigue is debilitating directly impacting both psychological and physical quality of life and a key driver in discontinuation of therapy. Lifestyle interventions targeting diet and exercise have evidence for improving fatigue in early stage breast cancer, however whether these strategies are efficacious for improving outcomes in women with advanced breast cancer remains unknown, with even less information for women from underrepresented backgrounds, who suffer disproportionately from breast cancer and its treatment. Research regarding the impact of these strategies on high grade fatigue induced by CDK4/6 inhibitors in advanced disease from a diverse patient population are needed. The prolonged overnight Fasting and/or Exercise on fatigue and other patient reported outcomes in women with hormone Receptor positive advanced breast cancer (FastER) study, will evaluate a phase II, 2 x 2 randomized controlled trial testing the effects of a prolonged overnight fasting (POF) intervention alone, moderate-intensity exercise alone, or in combination, on fatigue in 260 women with advanced breast cancer initiating treatment with hormonal therapy in combination with a CDK4/6 inhibitor. Participants would undergo assessment of fatigue and associated inflammatory biomarkers, as well as assessment of physical activity, diet, physical function, body composition and patient reported outcomes at baseline (prior to the initiation of CDK4/6 inhibitor) and 12 weeks (post-intervention), 6 and 12 months after study enrollment. The primary outcome of the study is to evaluate the impact of the interventions (vs control) on fatigue in women at 12 weeks. Secondary outcomes include inflammatory biomarkers, patient-reported outcomes, physical function and body composition. The FastER study will also explore the impact of the intervention on circadian rhythms, fatigue, sleep, depression, anxiety, quality of life, physical function and body composition. The overarching goal of the FastER study is to determine whether prolonged overnight fasting or moderate- intensity exercise alone or in combination can mitigate the adverse consequences of treatment and improve fatigue and other outcomes, in women with advanced breast cancer treated with CDK4/6 inhibitors to ultimately improve both quantity and quality of life for this growing population of women.

摘要 每年有4万多名妇女死于转移性乳腺癌。这些肿瘤中的大多数是激素 受体阳性（HR+），接受细胞周期蛋白依赖性激酶4/6（CDK 4/6）抑制剂联合治疗 芳香酶抑制剂或氟维司群有了这些治疗，晚期乳腺癌的女性 寿命更长，但不可避免地发生治疗相关的毒性，生活质量受到药物副作用的限制。 可能导致剂量减少和延迟的癌症治疗。疲劳是最常见的不良反应 服用CDK 4/6抑制剂的女性报告的副作用可能与 炎症当不受管理时，疲劳会使人衰弱，直接影响心理和身体 生活质量和停止治疗的关键驱动因素。针对饮食和运动的生活方式干预 有证据表明可以改善早期乳腺癌患者的疲劳，但是这些策略是否 对于改善晚期乳腺癌妇女的预后是否有效仍不清楚， 为来自代表性不足背景的妇女提供信息，她们患乳腺癌的比例过高 以及它的治疗。关于这些策略对CDK 4/6诱导的高度疲劳的影响的研究 需要来自不同患者群体的晚期疾病的抑制剂。 疲劳和其他患者报告的长时间整夜空腹和/或运动 激素受体阳性晚期乳腺癌（FastER）研究的女性结局，将 评估一项II期、2 × 2随机对照试验，测试延长过夜禁食（POF）的影响 单独干预、单独中等强度运动或两者结合对260名女性疲劳的影响 晚期乳腺癌，开始接受激素疗法联合CDK 4/6抑制剂治疗。 参与者将接受疲劳和相关炎症生物标志物的评估，以及 评估体力活动、饮食、身体功能、身体成分和患者报告的结局， 基线（开始CDK 4/6抑制剂治疗前）和12周（干预后），干预后6个月和12个月 研究入组。研究的主要结果是评估干预措施的影响（与对照组相比） 在怀孕12周的妇女中进行疲劳试验。次要结局包括炎症生物标志物、患者报告的 结果，身体功能和身体成分。FastER研究还将探讨 对昼夜节律、疲劳、睡眠、抑郁、焦虑、生活质量、身体机能和身体的干预 混合物. FastER研究的首要目标是确定是否延长过夜禁食或适度禁食。 单独或组合的强度运动可以减轻治疗的不良后果， 疲劳和其他结果，在接受CDK 4/6抑制剂治疗，最终 提高这一不断增长的妇女人口的生活数量和质量。