Exercise in Regional Breast Cancer With Neoadjuvant Anthracycline- Based Chemotherapy and Immunotherapy With Checkpoint-Inhibition
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 120
- 试验地点
- 4
- 主要终点
- Peak oxygen consumption (VO2peak) from baseline until the end of intervention
研究概览
简要总结
This is a prospective, randomized, controlled mono-center study investigating the effects of a combined, supervised aerobic exercise and resistance training in female patients with newly diagnosed, therapy-naive triple-negative breast cancer (TNBC, stage I-III) between 18 and 50 years of age scheduled for anthracycline-based chemotherapy and immunotherapy with checkpoint inhibitors. All patients will receive smart watches for rhythm monitoring.
Patients will be randomized (1:1) into a control group, receiving 24 weeks of standard exercise recommendations during neoadjuvant therapy, and an intervention group receiving 24 weeks of home-based, video-supervised exercise training consisting of endurance and resistance training. The primary endpoint is the change of peak oxygen consumption (VO2peak) between baseline and 24 weeks in the groups. Secondary endpoints include changes of physical function (short physical performance battery, SPPB), as well as cardiac biomarkers, quality of life, and changes of strength of the upper and lower body between baseline and 24 weeks. In addition, variables of cardiopulmonary exercise testing (CPET), resting and stress echocardiography, and burden of atrial fibrillation (AF) will be assessed. All changes in variables will be analyzed from baseline until 52 weeks as well.
Both groups will receive standard exercise recommendations after 24 weeks and will be followed-up by clinical examination after 52 weeks. Echocardiographic variables (at rest and during exercise), quality of life, CPET, SPPB, strength testing, burden of AF, and cardiac biomarkers will be assessed. Changes between the end of the intervention period 24 weeks after diagnosis and the end of follow-up after 52 weeks will be analyzed. In addition, changes in variables between baseline and 52 weeks will be analyzed.
As an exploratory endpoint the incidence of cancer therapy-related cardiac dysfunction (CTRCD) and immune-checkpoint inhibitor- associated myocarditis (ICI-myocarditis) will be assessed after 24 and 52 weeks.
详细描述
This is a prospective, randomized, controlled mono-center study investigating the effects of a combined, supervised aerobic exercise and resistance training in female patients with newly diagnosed TNBC (stage I-III) between 18 and 65 years of age scheduled for anthracycline-based chemotherapy and immunotherapy with checkpoint inhibitors. All patients will receive smart watches for rhythm monitoring. Patients will be advised to trigger electrocardiogram (ECG) measurements every day at 8 a.m., 2 p.m. and 8 p.m. as well as before and immediately after every training session (intervention group only). In addition, ECG should be recorded whenever symptoms occur.
Patients will be randomized (1:1) into a control group, receiving 24 weeks of standard exercise recommendations during neoadjuvant therapy, and an intervention group receiving 24 weeks of home-based, video-supervised exercise training consisting of endurance and resistance training.
At baseline clinical examination, quality of life, cardiac biomarkers, resting and stress echocardiography and CPET will be performed. SPPB and strength of the upper and lower body will be assessed.
Training in the intervention group will be performed 5x/week with 20 minutes/session and will contain resistance training and endurance training as a mixture between moderate continuous and high-intensity interval training. Training corridors based on heart rate will be prescribed with the aid of CPET testing at baseline and during follow-up visits. Intensity will be progressively increased, but will be individually adapted to the schedule and response to chemo- and immunotherapy.
Follow-up visits will be performed six and twelve weeks after diagnosis and clinical examination, cardiac biomarkers, resting and stress echocardiography and CPET as well as testing of muscle strength, SPPB, and quality of life will be repeated. Prescribed training corridors of heart rate will be adapted after each test. Upon clinical suspicion for adverse events, such as ICI-myocarditis, magnetic resonance imaging of the heart will be performed and training will not be continued.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Double (Investigator, Outcomes Assessor)
盲法说明
The principal investigator, who will assess outcomes, will be blinded to group allocation. Patients will be randomized by a staff member. Data analysis will be done by a professional statistician.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female patients with newly diagnosed, local triple-negative breast cancer (stage I-III) ≥ 18 to 65 years of age scheduled for immunochemotherapy with pembrolizumab and anthracycline-based chemotherapy
排除标准
- •Unstable cardiac condition (clinical suspicion of progress or unstable coronary artery disease, signs of acute heart failure, haemodynamically relevant arrhythmias)
- •Orthopaedic disability to exercise
结局指标
主要结局
Peak oxygen consumption (VO2peak) from baseline until the end of intervention
时间窗: 24 weeks
Difference of VO2peak between baseline to the end of intervention per group
次要结局
- VO2peak from baseline to the end of follow-up(52 weeks)
- VO2peak from the end of intervention to the end of follow-up(28 weeks)
- Burden of atrial fibrillation (AF) from baseline to the end of intervention(24 weeks)
- Burden of AF from baseline to the end of follow-up(52 weeks)
- Burden of AF from the end of intervention to the end of follow-up(28 weeks)
- Performance in short physical performance battery (SPPB) from baseline to end of intervention(24 weeks)
- Performance in SPPB from the end of intervention to the end of follow-up(28 weeks)
- Performance in SPPB from baseline to the end of follow-up(52 weeks)
- Improvement of muscle strength of the upper (biceps curl) and lower extremity (knee extensor) from baseline to the end of intervention(24 weeks)
- Improvement of muscle strength of the upper (biceps curl) and lower extremity (knee extensor) from baseline to the end of follow-up(52 weeks)
- Improvement of muscle strength of the upper (biceps curl) and lower extremity (knee extensor) from the end of intervention to the end of follow-up(28 weeks)
- Changes of resting and stress echocardiographic variables from baseline to the end of intervention(24 weeks)
- Changes of resting and stress echocardiographic variables from baseline to the end of follow-up(52 weeks)
- Changes of resting and stress echocardiographic variables from the end of intervention to the end of follow-up(28 weeks)
- Cardiac biomarkers from baseline to the end of intervention(24 weeks)
- Cardiac biomarkers from the end of intervention to the end of follow-up(28 weeks)
- Cardiac biomarkers from baseline to the end of follow-up(52 weeks)
- Change in quality of life from baseline to the end of intervention(24 weeks)
- Change in quality of life from the end of intervention to the end of follow-up(28 weeks)
- Change in quality of life from baseline to the end of follow-up(52 weeks)
- Incidence of immune-checkpoint inhibitor associated myocarditis (ICI-myocarditis) from baseline to the end of follow-up(52 weeks)
- Decrease of minute ventilation to carbon dioxide production (VE/VCO2) from baseline to the end of intervention(24 weeks)
- Decrease of VE/VCO2 from baseline to the end of follow-up(52 weeks)
- Decrease of VE/VCO2 from the end of intervention to the end of follow-up(28 weeks)
- Incidence of cancer treatment-related cardiac dysfunction (CTRCD) from baseline to the end of follow-up(52 weeks)