Clinical trial NCT06881940: Cardiac Rehabilitation Program on the Prevention of Cardiotoxicity in Breast Cancer Patients Undergoing Treatment With Anthracyclines and/or Trastuzumab
Official title: Rationale and Design of a Cardiac Rehabilitation Program on the Prevention of Cardiotoxicity in Breast Cancer Patients Undergoing Treatment With Anthracyclines and/or Trastuzumab: A Randomized, Active Control Group, Open-Label Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Cancer Therapy-Related Cardiac Dysfunction
Keywords: Rehabilitation
Breast Neoplasms
Cardiotoxicity
Trastuzumab
Anthracyclines
Lead sponsor: Instituto Nacional de Cardiologia Ignacio Chavez
Sponsor class: OTHER
Collaborators: name: Instituto Nacional de Cancerologia de Mexico
First posted: 2025-03-18
Enrollment: 284
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Interventional Model: Active Control Group Interventional Model Description: The risk exposure factors for the experimental group and the control group are the same Masking: None (Open Label) Allocation: Randomized
Primary purpose: PREVENTION

Brief summary: This study aims to evaluate the effectiveness of a cardiac rehabilitation protocol, incorporating aerobic and resistance exercise, in reducing the incidence of cardiotoxicity in breast cancer patients receiving treatment with anthracyclines and/or trastuzumab through a randomized, active control group, open-label clinical trial.

Detailed description: This is a randomized, open-label, with an active control group trial. This study adopts the main evaluation indicator being the incidence of cardiac dysfunction or heart failure as a manifestation of cardiovascular toxicity, assessed following the 2022 European Society of Cardiology (ESC) definitions for cancer-related therapy cardiac dysfunction (CTRCD).

Participants who pass the inclusion criteria through research will provide written informed consent to take part in the study. Once consent is obtained, participants will be randomly assigned to one of two study groups using a simple randomization process. This will be accomplished through a computer-generated random number sequence list, which will be managed by a designated investigator from the research team. The intervention group will receive standard oncological treatment combined with an aerobic and resistance exercise program, following the FITT principle (Frequency, Intensity, Type, and Time) for exercise prescription. Three out of five weekly sessions will be conducted per week. The control group will continue standard oncological treatment in addition to general recommendations regarding diet and physical activity but without a structured exercise protocol. During the treatment process, both branches of the trial will be followed over a 12 months period, with scheduled outpatient evaluations to assess biochemical parameters, a 12-lead electrocardiogram (ECG), a transthoracic echocardiogram (TTE), and a cardiopulmonary exercise test (CPET). Both the intervention and control groups will undergo these assessments at four key time points: baseline (defined as the time before the start of the chemotherapy regime and after the study enrollment), 3 months, 6 months, and 12 months post-initiation of chemotherapy. The main outcome of this clinical trial is a composite of incident cardiotoxicity, defined according to the ESC guidelines. Other cardiac function related indicators such as symptomatic congestive heart failure or asymptomatic but decreased left ventricular ejection fraction (LVEF) or global longitudinal strain (GLS) and changes in cardiac biomarkers will be evaluated to determine the occurrence of cardiac toxicity. Secondary outcomes assessed the impact on echocardiographic parameters of cardiac function, fluctuations in biomarkers and blood tests, cardiorespiratory performance, the impact of quality of life and explore the role of traditional cardiovascular risk factors.

Eligibility criteria: Inclusion Criteria:

* Women aged between 18 and 70 years will be considered eligible.
* Active residents of any municipality within Mexico City and the surrounding metropolitan area will qualify, conditioned that their maximum travel time from their residence to our recruitment center does not exceed three hours using private or public transportation. This criterion is established to ensure adherence to the protocol and availability for participation in the required interventions and assessments throughout the study.
* Patients diagnosed with early-stage or locally advanced breast cancer (stages I, II, or III, according to the TNM classification-Tumor, Node, Metastasis) who will undergo treatment with anthracyclines and/or adjuvant/neoadjuvant anti-HER2 therapy will be included. Participants must be scheduled to receive pharmacological treatment, ensuring that the study focuses on a population undergoing specific therapies for breast cancer management.
* Candidates must have the capacity, availability, and willingness to participate in an aerobic and resistance exercise program. Participants are required to possess both the physical ability and the willingness to actively engage in a structured exercise program, which includes aerobic and resistance activities essential to the study's objectives.
* Patients will provide informed written consent to participate in the study. To uphold ethical research principles and ensure the protection of participants' rights, all patients must voluntarily give their informed consent after receiving comprehensive information regarding the study's objectives, procedures, benefits, and potential risks.

Exclusion Criteria:

* Metastatic disease: Individuals with medical or imaging evidence of metastasis to any peripheral organ.
* Cardiovascular disease: Patients with a self-reported history of cardiovascular conditions, such as heart failure or uncontrolled hypertension, that may limit their ability to safely engage in physical activity. Additionally, those with peripheral arterial disease or valvular heart disease will not be eligible.
* Ischemic heart disease: Patients with a history of ischemic heart disease.
* Neurological disorders: Individuals with self-reported neurological diseases that significantly impair coordination, balance, or motor control, such as advanced Parkinson's disease, late-stage multiple sclerosis, or paralysis, making physical activity unsafe.
* Musculoskeletal conditions: Patients with self-reported musculoskeletal injuries or disorders that hinder physical activity, including fractures within the last five years, moderate to severe sprains, tendinitis, or severe arthritis.
* Uncontrolled systemic comorbidities: Individuals with decompensated systemic conditions, including heart failure, chronic kidney disease, or poorly controlled diabetes, will be excluded.
* Severe respiratory diseases: Patients with severe respiratory conditions that prevent physical exercise participation.
* Physical limitations: Individuals with mobility impairments or conditions requiring constant assistance for basic physical activities, such as those using assistive devices (e.g., wheelchairs, walkers) or with limb amputations, will not be eligible for participation.
* Severe psychiatric disorders: Patients with uncontrolled psychiatric conditions, including schizophrenia, severe bipolar disorder, or major depressive disorder, that may interfere with their ability to actively participate in a supervised exercise program.

Elimination Criteria:

* Voluntary withdrawal from the protocol.
* Development of severe cardiotoxicity requiring pharmacological treatment.
* Adverse reactions to chemotherapeutic agents.
* Disease progression according to the TNM classification during treatment.
* Failure to complete at least 80% of the prescribed adjuvant or neoadjuvant oncological treatment.
* Occurrence of adverse events during the study, such as falls or injuries.
* Death during the study period.
* Any accident related to the exercise protocol, including falls, sprains, or fractures.

Primary outcomes:
measure: Incidence of cardiac dysfunction or heart failure as a manifestation of cardiovascular toxicity in the intervention group and control group
timeFrame: From 1 week before starting oncological treatment to 1 year after the start of the chemotherapy regimen
Secondary outcomes:
measure: Impact on echocardiographic parameters
timeFrame: From 1 week before starting oncological treatment to 1 year after the start of the chemotherapy regimen
measure: Modification in series of circulating cardiac biomarkers
timeFrame: From 1 week before starting oncological treatment to 1 year after the start of the chemotherapy regimen
measure: Evaluation of cardiorespiratory performance
timeFrame: From 1 week before starting oncological treatment to 1 year after the start of the chemotherapy regimen
measure: Quality of Life Questionnaire: FACT-B
timeFrame: From 1 week before starting oncological treatment to 1 year after the start of the chemotherapy regimen
measure: Explore the role of traditional cardiovascular risk factors
timeFrame: From 1 week before starting oncological treatment to 1 year after the start of the chemotherapy regimen
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: National Institute of Cancerology (INCAN)
state: Cdmx
city: Mexico City
country: Mexico
facility: Instituto Nacional de Cancerología (INCAN)
Study officials:
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