Cardiac Rehabilitation Program on the Prevention of Cardiotoxicity in Breast Cancer Patients Undergoing Treatment with Anthracyclines And/or Trastuzumab (CARPTOX-BC)

March 14, 2025 updated by: Nilda Gladys Espinola Zavaleta, Instituto Nacional de Cardiologia Ignacio Chavez

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

284

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Nilda G. Espinola-Zavaleta, M.D., Ph.D
  • Phone Number: 21001 +525555732911
  • Email: niesza2001@hotmail.com

Study Contact Backup

Study Locations

  • Mexico
      • Mexico City, Mexico, 14080
        • Instituto Nacional de Cancerología (INCan)
        • Contact:
        • Contact:
        • Contact:
          • Neftali Eduardo Antonio-Villa, M.D., Ph.D.
    • Cdmx
      • Mexico City, Cdmx, Mexico, 14080
        • National Institute of Cancerology (INCAN)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard of care
Participants randomized to observational arm will receive standard oncological follow up and care.
Other: No Rehabilitation Program
The control group will continue standard oncological treatment in addition to general recommendations regarding diet and physical activity, but without a structured exercise protocol.
Experimental: Rehabilitation Program
Intervention arm receives standard oncological follow up and care + Rehabilitation Program
Other: Rehabilitation Program

Three of the five weekly sessions will take place at the gym in the Functional Unit of Breast Tumors at INCAN, under the supervision of Physical and Sports Medicine specialists and three physical therapists. These sessions allow for personalized feedback, enabling participants to confidently perform prescribed aerobic exercises at home on the remaining two days.

Each session starts with a 10- to 15-minute warm-up focused on joint mobility. Aerobic training is conducted at moderate intensity (40-59% VO2max or heart rate reserve), monitored with a Polar® FT1 device. Intensity is periodically adjusted based on the Borg Rating of Perceived Exertion and the talk test. Over 4-6 weeks, session duration will gradually increase to 90 minutes per week, remaining consistent thereafter.

Following aerobic training, resistance exercises targeting major muscle groups are performed using gym machines and dumbbells. The program includes seven exercises, progressively increasing load over 3-4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of cardiac dysfunction or heart failure as a manifestation of cardiovascular toxicity in the intervention group and control group
Time Frame: From 1 week before starting oncological treatment to 1 year after the start of the chemotherapy regimen
Calculate the incidence of cardiotoxicity associated with anthracycline and/or trastuzumab treatment of two groups following the 2022 European Society of Cardiology (ESC) definitions for cancer-related therapy cardiac dysfunction (CTRCD). LVEF greater than 50% with a relative GLS decrease exceeding 15% and/or a new rise in cardiac biomarkers. LVEF will be determined using Simpson's biplane method, incorporating apical four- and two-chamber views, while 2D-GLS measurements will be performed via velocity vector imaging. All echocardiographic evaluations will be conducted using a Siemens-Acuson 2000 system by a single expert in echocardiography, with results subsequently verified by a second expert to ensure accuracy and reliability. The classification of symptomatic congestive heart failure encompasses, but is not limited to, the presence of one or more of the following clinical manifestations: moist crackles in the lungs, bilateral anterior tibial edema, or lip cyanosis.
From 1 week before starting oncological treatment to 1 year after the start of the chemotherapy regimen

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Impact on echocardiographic parameters
Time Frame: From 1 week before starting oncological treatment to 1 year after the start of the chemotherapy regimen
This study aims to evaluate cardiac function by examining changes in echocardiographic parameters, including chamber volumes, diameters, diastolic function, right ventricular function, and both biventricular and auricular global longitudinal strain (GLS).
From 1 week before starting oncological treatment to 1 year after the start of the chemotherapy regimen
Modification in series of circulating cardiac biomarkers
Time Frame: From 1 week before starting oncological treatment to 1 year after the start of the chemotherapy regimen
Classical biomarkers of cardiac injury: C-reactive protein, Troponin I, B-type natriuretic peptide (NT-Pro BNP).
From 1 week before starting oncological treatment to 1 year after the start of the chemotherapy regimen
Evaluation of cardiorespiratory performance
Time Frame: From 1 week before starting oncological treatment to 1 year after the start of the chemotherapy regimen
The study will investigate modifications in cardiorespiratory fitness by measuring peak oxygen uptake (VO2max) through a cardiopulmonary exercise test (CPET) conducted on a bicycle ergometer with individualized workload adjustments.
From 1 week before starting oncological treatment to 1 year after the start of the chemotherapy regimen
Quality of Life Questionnaire: FACT-B
Time Frame: From 1 week before starting oncological treatment to 1 year after the start of the chemotherapy regimen
Investigators should evaluate the quality of life of the patient with QOL questionnaire (FACT-B)
From 1 week before starting oncological treatment to 1 year after the start of the chemotherapy regimen
Explore the role of traditional cardiovascular risk factors
Time Frame: From 1 week before starting oncological treatment to 1 year after the start of the chemotherapy regimen
This research will explore the role of conventional cardiovascular risk factors-including smoking, lipid levels, systemic arterial hypertension, diabetes, obesity, sedentary behavior, and the Framingham risk score-as potential mediators in the development of cardiotoxicity.
From 1 week before starting oncological treatment to 1 year after the start of the chemotherapy regimen

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto Nacional de Cardiologia Ignacio Chavez

Collaborators

Instituto Nacional de Cancerologia de Mexico

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 1, 2025

Primary Completion (Estimated)

December 1, 2028

Study Completion (Estimated)

December 1, 2029

Study Registration Dates

First Submitted

March 5, 2025

First Submitted That Met QC Criteria

March 14, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 14, 2025

Last Verified

December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 24-1488

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Can apply to researchers

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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