Exercise in Triple- Negative Breast Cancer
- Conditions
- Cancer, Breast
- Registration Number
- NCT06672120
- Lead Sponsor
- Technical University of Munich
- Brief Summary
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.
- Detailed Description
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 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 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.
The primary endpoint is the change of VO2peak between baseline and 24 weeks in the groups. Secondary endpoints include changes of variables between baseline and 24 weeks, including SPPB, cardiac biomarkers, quality of life, changes of strength of the upper and lower body (knee extensor and biceps muscles), variables of CPET, resting and stress echocardiography, and burden of AF. Changes in variables between baseline and after 52 weeks will also be analyzed. 24h- Holter monitoring will be performed at the end of weeks 24 and 52.
Both groups will receive standard exercise recommendations after 24 weeks and will be followed-up by clinical examination after 52 weeks: Resting and stress echocardiography, quality of life, CPET, SPPB, strength testing, AF burden, and cardiac biomarkers will be re-assessed.
As an exploratory endpoint the incidence CTRCD and ICI-myocarditis will be assessed after 24 and 52 weeks.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 120
- Female patients with newly diagnosed, local triple-negative breast cancer (stage I-III) ≥ 18 to 50 years of age scheduled for immunochemotherapy with pembrolizumab and anthracycline-based chemotherapy
- Unstable cardiac condition (clinical suspicion of progress or unstable coronary artery disease, signs of acute heart failure, haemodynamically relevant arrhythmias)
- Orthopaedic disability to exercise
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Peak oxygen consumption (VO2peak) from baseline until the end of intervention 24 weeks Difference of VO2peak between baseline to the end of intervention per group
- Secondary Outcome Measures
Name Time Method VO2peak from baseline to the end of follow-up 52 weeks Difference of VO2peak between baseline to the end of follow-up per group
VO2peak from the end of intervention to the end of follow-up 28 weeks Difference of VO2peak between the end of intervention and the end of follow-up per group
Burden of atrial fibrillation (AF) from baseline to the end of intervention 24 weeks Burden of AF will be assessed with 24h-Holter monitoring at the end of week 24 and with patient-triggered documentation through smart watch monitoring. ECG triggering will be done every day throughout the study at 8 a.m., 2 p.m., 8 p.m., before and immediately after exercise, or with perceived symptoms
Burden of AF from baseline to the end of follow-up 52 weeks Burden of AF will be assessed with 24h-Holter monitoring at the end of week 24 and 52 and with patient-triggered documentation through smart watch monitoring. ECG triggering will be done every day throughout the study at 8 a.m., 2 p.m., 8 p.m., before and immediately after exercise, or with perceived symptoms
Burden of AF from the end of intervention to the end of follow-up 28 weeks Burden of AF will be assessed with 24h-Holter monitoring at the end of week 24 and 52 and with patient-triggered documentation through smart watch monitoring. ECG triggering will be done every day throughout the study at 8 a.m., 2 p.m., 8 p.m., before and immediately after exercise, or with perceived symptoms
Performance in short physical performance battery (SPPB) from baseline to end of intervention 24 weeks Values range from 0 (worst performance) to 12 (best performance)
Performance in SPPB from the end of intervention to the end of follow-up 28 weeks Values range from 0 (worst performance) to 12 (best performance)
Performance in SPPB from baseline to the end of follow-up 52 weeks Values range from 0 (worst performance) to 12 (best performance)
Improvement of muscle strength of the upper (biceps curl) and lower extremity (knee extensor) from baseline to the end of intervention 24 weeks A one repetition maximum test (1 RPM) will be done for both tests
Improvement of muscle strength of the upper (biceps curl) and lower extremity (knee extensor) from baseline to the end of follow-up 52 weeks 1 RPM will be done for both tests
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 1 RPM will be done for both tests
Changes of resting and stress echocardiographic variables from baseline to the end of intervention 24 weeks Left ventricular ejection fraction will be measured at rest and peak exercise
Changes of resting and stress echocardiographic variables from baseline to the end of follow-up 52 weeks Left ventricular ejection fraction will be measured at rest and peak exercise
Changes of resting and stress echocardiographic variables from the end of intervention to the end of follow-up 28 weeks Left ventricular ejection fraction will be measured at rest and peak exercise
Cardiac biomarkers from baseline to the end of intervention 24 weeks Change in troponin I and NTproBNP from baseline to the end of intervention
Cardiac biomarkers from the end of intervention to the end of follow-up 28 weeks Change in troponin I and NTproBNP from the end of intervention to the end of follow-up
Cardiac biomarkers from baseline to the end of follow-up 52 weeks Change in troponin I and NTproBNP from baseline to the end of follow-up
Change in quality of life from baseline to the end of intervention 24 weeks Change in EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire). Values range from 0 to 100, with 100 showing the best quality of life and 0 the worst.
Change in quality of life from the end of intervention to the end of follow-up 28 weeks Change in EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire). Values range from 0 to 100, with 100 showing the best quality of life and 0 the worst.
Change in quality of life from baseline to the end of follow-up 52 weeks Change in EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire). Values range from 0 to 100, with 100 showing the best quality of life and 0 the worst.
Incidence of immune-checkpoint inhibitor associated myocarditis (ICI-myocarditis) from baseline to the end of follow-up 52 weeks ICI myocarditis is defined as signs of myocarditis on magnetic resonance imaging of the heart according to the modified Lake Louis criteria and positive troponin I levels or positive troponin levels and two additional side criteria (clinical symptoms, reduction in left ventricular ejection fraction, strain, or wall motion abnormalities, or other immune-related side effects, or arrhythmias)
Decrease of minute ventilation to carbon dioxide production (VE/VCO2) from baseline to the end of intervention 24 weeks Change in VE/VCO2 during CPET
Decrease of VE/VCO2 from baseline to the end of follow-up 52 weeks Change in VE/VCO2 during CPET
Decrease of VE/VCO2 from the end of intervention to the end of follow-up 28 weeks Change in VE/VCO2 during CPET
Incidence of cancer treatment-related cardiac dysfunction (CTRCD) from baseline to the end of follow-up 52 weeks CTRCD is defined as a reduction of left ventricular ejection fraction ≥10% to 40-49% OR a reduction of \<10% to 40-49% AND a decline of strain \>15% of the baseline OR a new rise cardiac biomarkers
Trial Locations
- Locations (2)
Preventive Sports Medicine and Sports Cardiology
🇩🇪Munich, Bavaria, Germany
Department of Medicine, Division of Prevention and Sports Medicine TU Munich
🇩🇪Munich, Germany