Cardiac Rehabilitation Program on the Prevention of Cardiotoxicity in Breast Cancer Patients Undergoing Treatment With Anthracyclines and/or Trastuzumab

NCT06881940 | Not Yet Recruiting DMC

• 1 other identifier: 24-1488
• Study Type: interventional
• Target: 284
• Locations: 1 country
• Sites: 2

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.

Conditions

Cancer Therapy-Related Cardiac Dysfunction

Keywords

Rehabilitation; Breast Neoplasms; Cardiotoxicity; Trastuzumab; Anthracyclines

Outcome Measures

Primary Outcomes (1)

• Incidence of cardiac dysfunction or heart failure as a manifestation of cardiovascular toxicity in the intervention group and control group

  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 Outcomes (5)

• Impact on echocardiographic parameters

  From 1 week before starting oncological treatment to 1 year after the start of the chemotherapy regimen

• Modification in series of circulating cardiac biomarkers

  From 1 week before starting oncological treatment to 1 year after the start of the chemotherapy regimen

• Evaluation of cardiorespiratory performance

  From 1 week before starting oncological treatment to 1 year after the start of the chemotherapy regimen

• Quality of Life 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

  From 1 week before starting oncological treatment to 1 year after the start of the chemotherapy regimen

Study Arms (2)

Standard of care

ACTIVE COMPARATOR

Participants randomized to observational arm will receive standard oncological follow up and care.

Other: No Rehabilitation Program

Rehabilitation Program

EXPERIMENTAL

Intervention arm receives standard oncological follow up and care + Rehabilitation Program

Other: Rehabilitation Program

Interventions

Rehabilitation Program OTHER

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.

Rehabilitation Program

No Rehabilitation Program OTHER

The control group will continue standard oncological treatment in addition to general recommendations regarding diet and physical activity, but without a structured exercise protocol.

Standard of care

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Instituto Nacional de Cardiologia Ignacio Chavez: lead
• Instituto Nacional de Cancerologia de Mexico: collaborator

Study Sites (2)

Instituto Nacional de Cancerología (INCAN)

Mexico City, Mexico City, 14080, Mexico

Location

National Institute of Cancerology (INCAN)

Mexico City, Mexico City, 14080, Mexico

Location

Related Publications (25)

• Kerrigan DJ, Reddy M, Walker EM, Cook B, McCord J, Loutfi R, Saval MA, Baxter J, Brawner CA, Keteyian SJ. Cardiac Rehabilitation Improves Fitness in Patients With Subclinical Markers of Cardiotoxicity While Receiving Chemotherapy: A RANDOMIZED CONTROLLED STUDY. J Cardiopulm Rehabil Prev. 2023 Mar 1;43(2):129-134. doi: 10.1097/HCR.0000000000000719. Epub 2022 Aug 4.

  PMID: 35940850 BACKGROUND

• Viamonte SG, Joaquim AV, Alves AJ, Vilela E, Capela A, Ferreira C, Duarte BF, Rato ND, Teixeira MP, Tavares A, Santos M, Ribeiro F. Cardio-Oncology Rehabilitation for Cancer Survivors With High Cardiovascular Risk: A Randomized Clinical Trial. JAMA Cardiol. 2023 Dec 1;8(12):1119-1128. doi: 10.1001/jamacardio.2023.3558.

  PMID: 37819656 BACKGROUND

• Diaz-Balboa E, Pena-Gil C, Rodriguez-Romero B, Cuesta-Vargas AI, Lado-Baleato O, Martinez-Monzonis A, Pedreira-Perez M, Palacios-Ozores P, Lopez-Lopez R, Gonzalez-Juanatey JR, Gonzalez-Salvado V. Exercise-based cardio-oncology rehabilitation for cardiotoxicity prevention during breast cancer chemotherapy: The ONCORE randomized controlled trial. Prog Cardiovasc Dis. 2024 Jul-Aug;85:74-81. doi: 10.1016/j.pcad.2024.02.002. Epub 2024 Feb 21.

  PMID: 38395212 BACKGROUND

• Yang HL, Hsieh PL, Hung CH, Cheng HC, Chou WC, Chu PM, Chang YC, Tsai KL. Early Moderate Intensity Aerobic Exercise Intervention Prevents Doxorubicin-Caused Cardiac Dysfunction Through Inhibition of Cardiac Fibrosis and Inflammation. Cancers (Basel). 2020 Apr 28;12(5):1102. doi: 10.3390/cancers12051102.

  PMID: 32354131 BACKGROUND

• Kouzi SA, Uddin MN. Aerobic Exercise Training as a Potential Cardioprotective Strategy to Attenuate Doxorubicin-Induced Cardiotoxicity. J Pharm Pharm Sci. 2016 Jul-Sep;19(3):399-410. doi: 10.18433/J3JS5R.

  PMID: 27806245 BACKGROUND

• Yu AF, Jones LW. Breast cancer treatment-associated cardiovascular toxicity and effects of exercise countermeasures. Cardiooncology. 2016;2:1. doi: 10.1186/s40959-016-0011-5. Epub 2016 Feb 25.

  PMID: 28133540 BACKGROUND

• Xie S, Sun Y, Zhao X, Xiao Y, Zhou F, Lin L, Wang W, Lin B, Wang Z, Fang Z, Wang L, Zhang Y. An update of the molecular mechanisms underlying anthracycline induced cardiotoxicity. Front Pharmacol. 2024 Jun 26;15:1406247. doi: 10.3389/fphar.2024.1406247. eCollection 2024.

  PMID: 38989148 BACKGROUND

• Nebigil CG, Desaubry L. Updates in Anthracycline-Mediated Cardiotoxicity. Front Pharmacol. 2018 Nov 12;9:1262. doi: 10.3389/fphar.2018.01262. eCollection 2018.

  PMID: 30483123 BACKGROUND

• Angsutararux P, Luanpitpong S, Issaragrisil S. Chemotherapy-Induced Cardiotoxicity: Overview of the Roles of Oxidative Stress. Oxid Med Cell Longev. 2015;2015:795602. doi: 10.1155/2015/795602. Epub 2015 Sep 29.

  PMID: 26491536 BACKGROUND

• Herrmann J, Lenihan D, Armenian S, Barac A, Blaes A, Cardinale D, Carver J, Dent S, Ky B, Lyon AR, Lopez-Fernandez T, Fradley MG, Ganatra S, Curigliano G, Mitchell JD, Minotti G, Lang NN, Liu JE, Neilan TG, Nohria A, O'Quinn R, Pusic I, Porter C, Reynolds KL, Ruddy KJ, Thavendiranathan P, Valent P. Defining cardiovascular toxicities of cancer therapies: an International Cardio-Oncology Society (IC-OS) consensus statement. Eur Heart J. 2022 Jan 31;43(4):280-299. doi: 10.1093/eurheartj/ehab674.

  PMID: 34904661 BACKGROUND

• Wang Y, Wang Y, Han X, Sun J, Li C, Adhikari BK, Zhang J, Miao X, Chen Z. Cardio-Oncology: A Myriad of Relationships Between Cardiovascular Disease and Cancer. Front Cardiovasc Med. 2022 Mar 17;9:727487. doi: 10.3389/fcvm.2022.727487. eCollection 2022.

  PMID: 35369296 BACKGROUND

• Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gotzsche PC, Krleza-Jeric K, Hrobjartsson A, Mann H, Dickersin K, Berlin JA, Dore CJ, Parulekar WR, Summerskill WS, Groves T, Schulz KF, Sox HC, Rockhold FW, Rennie D, Moher D. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013 Feb 5;158(3):200-7. doi: 10.7326/0003-4819-158-3-201302050-00583.

  PMID: 23295957 BACKGROUND

• Campbell KL, Winters-Stone KM, Wiskemann J, May AM, Schwartz AL, Courneya KS, Zucker DS, Matthews CE, Ligibel JA, Gerber LH, Morris GS, Patel AV, Hue TF, Perna FM, Schmitz KH. Exercise Guidelines for Cancer Survivors: Consensus Statement from International Multidisciplinary Roundtable. Med Sci Sports Exerc. 2019 Nov;51(11):2375-2390. doi: 10.1249/MSS.0000000000002116.

  PMID: 31626055 BACKGROUND

• Gilchrist SC, Barac A, Ades PA, Alfano CM, Franklin BA, Jones LW, La Gerche A, Ligibel JA, Lopez G, Madan K, Oeffinger KC, Salamone J, Scott JM, Squires RW, Thomas RJ, Treat-Jacobson DJ, Wright JS; American Heart Association Exercise, Cardiac Rehabilitation, and Secondary Prevention Committee of the Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; and Council on Peripheral Vascular Disease. Cardio-Oncology Rehabilitation to Manage Cardiovascular Outcomes in Cancer Patients and Survivors: A Scientific Statement From the American Heart Association. Circulation. 2019 May 21;139(21):e997-e1012. doi: 10.1161/CIR.0000000000000679.

  PMID: 30955352 BACKGROUND

• Lavin-Perez AM, Collado-Mateo D, Hinojo Gonzalez C, de Juan Ferre A, Ruisanchez Villar C, Mayo X, Jimenez A. High-intensity exercise prescription guided by heart rate variability in breast cancer patients: a study protocol for a randomized controlled trial. BMC Sports Sci Med Rehabil. 2023 Mar 8;15(1):28. doi: 10.1186/s13102-023-00634-2.

  PMID: 36890601 BACKGROUND

• Antunes P, Joaquim A, Sampaio F, Nunes C, Ascensao A, Vilela E, Teixeira M, Capela A, Amarelo A, Marques C, Viamonte S, Alves A, Esteves D. Effects of exercise training on cardiac toxicity markers in women with breast cancer undergoing chemotherapy with anthracyclines: a randomized controlled trial. Eur J Prev Cardiol. 2023 Jul 12;30(9):844-855. doi: 10.1093/eurjpc/zwad063.

  PMID: 36857149 BACKGROUND

• Wilson RL, Christopher CN, Yang EH, Barac A, Adams SC, Scott JM, Dieli-Conwright CM. Incorporating Exercise Training into Cardio-Oncology Care: Current Evidence and Opportunities: JACC: CardioOncology State-of-the-Art Review. JACC CardioOncol. 2023 Oct 17;5(5):553-569. doi: 10.1016/j.jaccao.2023.08.008. eCollection 2023 Oct.

  PMID: 37969654 BACKGROUND

• Wallace KB, Sardao VA, Oliveira PJ. Mitochondrial Determinants of Doxorubicin-Induced Cardiomyopathy. Circ Res. 2020 Mar 27;126(7):926-941. doi: 10.1161/CIRCRESAHA.119.314681. Epub 2020 Mar 26.

  PMID: 32213135 BACKGROUND

• McGowan JV, Chung R, Maulik A, Piotrowska I, Walker JM, Yellon DM. Anthracycline Chemotherapy and Cardiotoxicity. Cardiovasc Drugs Ther. 2017 Feb;31(1):63-75. doi: 10.1007/s10557-016-6711-0.

  PMID: 28185035 BACKGROUND

• Li H, Wang M, Huang Y. Anthracycline-induced cardiotoxicity: An overview from cellular structural perspective. Biomed Pharmacother. 2024 Oct;179:117312. doi: 10.1016/j.biopha.2024.117312. Epub 2024 Aug 20.

  PMID: 39167843 BACKGROUND

• Lyon AR, Lopez-Fernandez T, Couch LS, Asteggiano R, Aznar MC, Bergler-Klein J, Boriani G, Cardinale D, Cordoba R, Cosyns B, Cutter DJ, de Azambuja E, de Boer RA, Dent SF, Farmakis D, Gevaert SA, Gorog DA, Herrmann J, Lenihan D, Moslehi J, Moura B, Salinger SS, Stephens R, Suter TM, Szmit S, Tamargo J, Thavendiranathan P, Tocchetti CG, van der Meer P, van der Pal HJH; ESC Scientific Document Group. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022 Nov 1;43(41):4229-4361. doi: 10.1093/eurheartj/ehac244. No abstract available.

  PMID: 36017568 BACKGROUND

• Farmakis D. Is cardio-oncology a rapidly growing field of precision medicine? Eur J Heart Fail. 2020 Dec;22(12):2310-2313. doi: 10.1002/ejhf.2051. Epub 2020 Nov 24. No abstract available.

  PMID: 33175447 BACKGROUND

• Dang CT, Yu AF, Jones LW, Liu J, Steingart RM, Argolo DF, Norton L, Hudis CA. Cardiac Surveillance Guidelines for Trastuzumab-Containing Therapy in Early-Stage Breast Cancer: Getting to the Heart of the Matter. J Clin Oncol. 2016 Apr 1;34(10):1030-3. doi: 10.1200/JCO.2015.64.5515. Epub 2016 Feb 1. No abstract available.

  PMID: 26834055 BACKGROUND

• Denlinger CS, Sanft T, Baker KS, Broderick G, Demark-Wahnefried W, Friedman DL, Goldman M, Hudson M, Khakpour N, King A, Koura D, Lally RM, Langbaum TS, McDonough AL, Melisko M, Montoya JG, Mooney K, Moslehi JJ, O'Connor T, Overholser L, Paskett ED, Peppercorn J, Pirl W, Rodriguez MA, Ruddy KJ, Silverman P, Smith S, Syrjala KL, Tevaarwerk A, Urba SG, Wakabayashi MT, Zee P, McMillian NR, Freedman-Cass DA. Survivorship, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2018 Oct;16(10):1216-1247. doi: 10.6004/jnccn.2018.0078.

  PMID: 30323092 BACKGROUND

• Camilli M, Cipolla CM, Dent S, Minotti G, Cardinale DM. Anthracycline Cardiotoxicity in Adult Cancer Patients: JACC: CardioOncology State-of-the-Art Review. JACC CardioOncol. 2024 Sep 17;6(5):655-677. doi: 10.1016/j.jaccao.2024.07.016. eCollection 2024 Oct.

  PMID: 39479333 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Cardiotoxicity

Interventions

Rehabilitation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Central Study Contacts

Nilda G. Espinola-Zavaleta, M.D., Ph.D

CONTACT

+525555732911; niesza2001@hotmail.com

Neftali Eduardo Antonio-Villa, M.D., Ph.D

CONTACT

+525555732911; eduardo.villa@cardiologia.org.mx

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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

Study Record Dates

• First Submitted: March 5, 2025
• First Posted: March 18, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: March 18, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

ME (2)