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.
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. 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
DOUBLE
Enrollment
120
Combined, home-based, supervised, video- assisted, endurance and resistance training
Preventive Sports Medicine and Sports Cardiology
Munich, Bavaria, Germany
RECRUITINGDepartment of Medicine, Division of Prevention and Sports Medicine TU Munich
Munich, Germany
RECRUITINGPeak oxygen consumption (VO2peak) from baseline until the end of intervention
Difference of VO2peak between baseline to the end of intervention per group
Time frame: 24 weeks
VO2peak from baseline to the end of follow-up
Difference of VO2peak between baseline to the end of follow-up per group
Time frame: 52 weeks
VO2peak from the end of intervention to the end of follow-up
Difference of VO2peak between the end of intervention and the end of follow-up per group
Time frame: 28 weeks
Burden of atrial fibrillation (AF) from baseline to the end of intervention
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
Time frame: 24 weeks
Burden of AF from baseline to the end of follow-up
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
Time frame: 52 weeks
Burden of AF from the end of intervention to the end of follow-up
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
Time frame: 28 weeks
Performance in short physical performance battery (SPPB) from baseline to end of intervention
Values range from 0 (worst performance) to 12 (best performance)
Time frame: 24 weeks
Performance in SPPB from the end of intervention to the end of follow-up
Values range from 0 (worst performance) to 12 (best performance)
Time frame: 28 weeks
Performance in SPPB from baseline to the end of follow-up
Values range from 0 (worst performance) to 12 (best performance)
Time frame: 52 weeks
Improvement of muscle strength of the upper (biceps curl) and lower extremity (knee extensor) from baseline to the end of intervention
A one repetition maximum test (1 RPM) will be done for both tests
Time frame: 24 weeks
Improvement of muscle strength of the upper (biceps curl) and lower extremity (knee extensor) from baseline to the end of follow-up
1 RPM will be done for both tests
Time frame: 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
1 RPM will be done for both tests
Time frame: 28 weeks
Changes of resting and stress echocardiographic variables from baseline to the end of intervention
Left ventricular ejection fraction will be measured at rest and peak exercise
Time frame: 24 weeks
Changes of resting and stress echocardiographic variables from baseline to the end of follow-up
Left ventricular ejection fraction will be measured at rest and peak exercise
Time frame: 52 weeks
Changes of resting and stress echocardiographic variables from the end of intervention to the end of follow-up
Left ventricular ejection fraction will be measured at rest and peak exercise
Time frame: 28 weeks
Cardiac biomarkers from baseline to the end of intervention
Change in troponin I and NTproBNP from baseline to the end of intervention
Time frame: 24 weeks
Cardiac biomarkers from the end of intervention to the end of follow-up
Change in troponin I and NTproBNP from the end of intervention to the end of follow-up
Time frame: 28 weeks
Cardiac biomarkers from baseline to the end of follow-up
Change in troponin I and NTproBNP from baseline to the end of follow-up
Time frame: 52 weeks
Change in quality of life from baseline to the end of intervention
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.
Time frame: 24 weeks
Change in quality of life from the end of intervention to the end of follow-up
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.
Time frame: 28 weeks
Change in quality of life from baseline to the end of follow-up
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.
Time frame: 52 weeks
Incidence of immune-checkpoint inhibitor associated myocarditis (ICI-myocarditis) from baseline to the end of follow-up
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)
Time frame: 52 weeks
Decrease of minute ventilation to carbon dioxide production (VE/VCO2) from baseline to the end of intervention
Change in VE/VCO2 during CPET
Time frame: 24 weeks
Decrease of VE/VCO2 from baseline to the end of follow-up
Change in VE/VCO2 during CPET
Time frame: 52 weeks
Decrease of VE/VCO2 from the end of intervention to the end of follow-up
Change in VE/VCO2 during CPET
Time frame: 28 weeks
Incidence of cancer treatment-related cardiac dysfunction (CTRCD) from baseline to the end of follow-up
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
Time frame: 52 weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.