Clinical trial NCT03964142: Exercise-based Cardiac Rehabilitation for the Prevention of Breast Cancer Chemotherapy-induced Cardiotoxicity
Official title: Randomized Controlled Trial on Comprehensive Exercise-based Cardiac Rehabilitation Programs for the Prevention of Anthracyclines and/or Anti-HER2 Antibodies-induced Cardiotoxicity in Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiotoxicity
Cardiac Rehabilitation
Keywords: Chemotherapy
Anthracyclines
Trastuzumab
Pertuzumab
Antibodies, Monoclonal, Humanized
Breast Cancer
Exercise therapy
Lead sponsor: Hospital Clinico Universitario de Santiago
Sponsor class: OTHER
Collaborators: name: Instituto de Salud Carlos III
First posted: 2019-05-28
Enrollment: 122
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This project aims to determine whether a comprehensive cardiac rehabilitation program including supervised exercise training is able to prevent cardiotoxicity during treatment with anthracyclines and / or anti-HER-2 antibodies in women with breast cancer. Participants will be randomly allocated to cardiac rehabilitation (intervention group) or conventional management with physical exercise recommendation (control group).

Detailed description: Cardiovascular toxicity caused by chemotherapy is the leading cause of death in patients who survive cancer. Physical exercise during chemotherapy has shown to improve quality of life and decrease the risk of death. The objective of this project is to determine whether an intervention through a comprehensive cardiac rehabilitation program including supervised physical exercise is able to prevent anthracyclines and / or anti-HER-2 antibodies-induced cardiotoxicity in women with breast cancer.

For this purpose, the investigators intend to conduct a randomized controlled study including female patients managed under the same cardiotoxicity prevention protocol (clinical, laboratory and echocardiographic follow-up assessment). Patients will be randomized to a non-pharmacological intervention (participation in a multidisciplinary cardiac rehabilitation program with supervised exercise training) or control (conventional management and physical activity recommendation)\*.

The investigators hypothesize that a cardiac rehabilitation program may limit chemotherapy-induced cardiotoxicity in women with breast cancer, improve cardiac remodeling assessed by echocardiography and enhance their global cardiovascular risk profile to a greater extent, compared to control group.

\* OF NOTE: Due to the COVID-19 pandemics, several modifications to the original protocol were introduced for safety reasons or motivated by the health situation, namely:

1. Intervention: Change from centre-based to telematic supervised exercise training sessions provided within the cardiac rehabilitation program (intervention group)
2. Secondary outcome 4: Change in functional capacity assessed by conventional ergometry or cardiopulmonary exercise test OR the 6-minute walking test (metabolic equivalents: METs or peak oxygen consumption: VO2)
3. Recruiting centres: One centre (Hospital Universitari Vall d'Hebron) withdrew from the study due to the impossibility of assuming its execution.

Eligibility criteria: Inclusion Criteria:

* First diagnosis of breast cancer at early stages (I, II, III)
* Treatment with anthracyclines and / or anti-HER-2 antibodies (trastuzumab and / or pertuzumab)
* Possibility of completing a cardiac rehabilitation program (centre-based or telematic) and programmed visits.
* Providing written informed consent.

Exclusion Criteria:

* Patients with previous history of heart disease or heart failure.
* Left ventricular dysfunction (left ventricular ejection fraction \<53%) at baseline.
* Metastatic disease.
* Patients carrying an implantable cardioverter defibrillator.
* Patients with physical or mental limitation to carry out an exercise program.

Primary outcomes:
measure: Change in left ventricular systolic function quantified by left ventricular ejection fraction and global longitudinal strain by transthoracic echocardiography
timeFrame: Baseline to every 3 months through study completion, at the end of the study at an average of 18 months, and every year after study completion up to a maximum of 5 years
Secondary outcomes:
measure: Change in health-related quality of life assessed by the Functional Assessment of Cancer Therapy - Breast plus Arm Morbidity (FACT-B+4) questionnaire
timeFrame: Baseline and at the end of the study at an average of 18 months
measure: Change in tolerance to chemotherapy: number of participants with significant cardiovascular and non-cardiovascular adverse effects throughout the study
timeFrame: Every 3 months during study completion and at the end of the study at an average of 18 months
measure: Change in global functional capacity assessed by conventional ergometry, cardiopulmonary exercise testing (CPET) or the 6-minute walking test (6MWT).
timeFrame: Baseline and at the end of the study at an average of 18 months
measure: Change in localized lower limb functional capacity assessed by number of repetitions performed within 30 seconds in the sit-to-stand test
timeFrame: Baseline and at the end of the study at an average of 18 months
measure: Change in shoulder functional capacity assessed by range of degrees in shoulder movement by goniometry
timeFrame: Baseline and at the end of the study at an average of 18 months
measure: Change in upper limb strength measured by dynamometry (kg)
timeFrame: Baseline and at the end of the study at an average of 18 months
measure: Change in shoulder pain and disability assessed by the SPADI (shoulder pain and disability index (SPADI) questionnaire
timeFrame: Baseline and at the end of the study at an average of 18 months
measure: Change in cardiovascular risk profile as assessed by the presence or absence of classic cardiovascular risk factors
timeFrame: Baseline and at the end of the study at an average of 18 months
measure: Change in anthropometric parameters: height in cm
timeFrame: Baseline and at the end of the study at an average of 18 months
measure: Change in anthropometric parameters: weight in kg
timeFrame: Baseline and at the end of the study at an average of 18 months
measure: Change in anthropometric parameters: body mass index (BMI) in kg/m^2
timeFrame: Baseline and at the end of the study at an average of 18 months
measure: Change in anthropometric parameters: abdominal circumference in cm
timeFrame: Baseline and at the end of the study at an average of 18 months
measure: Change in resting heart rate measured by pulse oximetry (beats per min)
timeFrame: Baseline and at the end of the study at an average of 18 months
measure: Change in resting blood pressure (mmHg) measured by sphygmomanometer
timeFrame: Baseline and at the end of the study at an average of 18 months
measure: Change in biomarkers NT-ProBNP
timeFrame: Baseline and at the end of the study at an average of 18 months
measure: Change in biomarkers: troponin
timeFrame: Baseline and at the end of the study at an average of 18 months
measure: Change in biomarkers: haemoglobin
timeFrame: Baseline and at the end of the study at an average of 18 months
measure: Change in dietary pattern as assessed by the PREDIMED (PREvención con DIeta MEDiterránea) questionnaire
timeFrame: Baseline and at the end of the study at an average of 18 months
measure: Change in the score for depression assessed by Zigmond and Snaith questionnaire to rate anxiety and depression
timeFrame: Baseline and at study completion at an average of 18 months, plus at the end of training (at an average of 12 to 15 months) in the intervention group
measure: Change in the score for anxiety assessed by the Zigmond and Snaith questionnaire to rate depression and anxiety
timeFrame: Baseline and at study completion, plus at the end of training (at an average of 12 to 15 months) in the intervention group
measure: Change in physical activity (minutes of dedicated physical activity)
timeFrame: Baseline and at study completion at an average of 18 months
measure: Change in physical activity assessed by the score in the Godin Leisure Test Exercise Questionnaire (GLTEQ)
timeFrame: Baseline and at study completion at an average of 18 months
measure: Change in lymphedema assessed by perimeter of the upper limb by cirtometry (cm), stage and grade
timeFrame: Baseline after surgery and 2-4 weeks after the end of chemotherapy (at an average of 12 to 15 months)
Other outcomes:
measure: Adherence and compliance to cardiac rehabilitation program (intervention group) assessed by number of training sessions attended/ number of sessions planned
timeFrame: At the end of the cardiac rehabilitation program at an average of 12 to 15 months
measure: Security of the cardiac rehabilitation program assessed by number of adverse events during training (intervention group)
timeFrame: At the end of the cardiac rehabilitation program at an average of 12 to 15 months
measure: Changes in expectations regarding the cardiac rehabilitation program assessed by a questionnaire (intervention group)
timeFrame: Baseline and at the end of the cardiac rehabilitation program at an average of 12 to 15 months
measure: Satisfaction with the cardiac rehabilitation program assessed by a questionnaire (intervention group)
timeFrame: At the end of the cardiac rehabilitation program at an average of 12 to 15 months
Locations:
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago
state: A Coruña
Study officials:
affiliation: Cardiology Department, Hospital Clínico Universitario de Santiago, CIBER-CV
name: Amparo Martínez Monzonís, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cardiology Department, Hospital Clínico Universitario de Santiago, CIBER-CV
name: Carlos Peña Gil, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cardiology Department, Hospital Clínico Universitario de Santiago, CIBER-CV
name: José Ramón González Juanatey, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Diaz-Balboa E, Gonzalez-Salvado V, Rodriguez-Romero B, Martinez-Monzonis A, Pedreira-Perez M, Cuesta-Vargas AI, Lopez-Lopez R, Gonzalez-Juanatey JR, Pena-Gil C. Thirty-second sit-to-stand test as an alternative for estimating peak oxygen uptake and 6-min walking distance in women with breast cancer: a cross-sectional study. Support Care Cancer. 2022 Oct;30(10):8251-8260. doi: 10.1007/s00520-022-07268-z. Epub 2022 Jul 11.
citation: Diaz-Balboa E, Gonzalez-Salvado V, Rodriguez-Romero B, Martinez-Monzonis A, Pedreira-Perez M, Palacios-Ozores P, Lopez-Lopez R, Pena-Gil C, Gonzalez-Juanatey JR. A randomized trial to evaluate the impact of exercise-based cardiac rehabilitation for the prevention of chemotherapy-induced cardiotoxicity in patients with breast cancer: ONCORE study protocol. BMC Cardiovasc Disord. 2021 Apr 7;21(1):165. doi: 10.1186/s12872-021-01970-2.