Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Exercise-based Cardiac Rehabilitation for the Prevention of Breast Cancer Chemotherapy-induced Cardiotoxicity (ONCORE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03964142
Recruitment Status : Recruiting
First Posted : May 28, 2019
Last Update Posted : October 6, 2020
Sponsor:
Collaborator:
Instituto de Salud Carlos III
Information provided by (Responsible Party):
Carlos Peña Gil, Hospital Clinico Universitario de Santiago

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).

Condition or disease Intervention/treatment Phase
Cardiotoxicity Cardiac Rehabilitation Other: Cardiac rehabilitation Not Applicable

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 340 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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
Actual Study Start Date : August 1, 2018
Estimated Primary Completion Date : November 1, 2020
Estimated Study Completion Date : November 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cardiac Rehabilitation
Patients enrolled in the integrated exercise-based cardiac rehabilitation program (centre-based or telematic)
Other: Cardiac rehabilitation

Integrated cardiac rehabilitation program that includes supervised exercise training*.

* Due to the COVID-19 pandemic, supervised physical exercise training had to be conducted telematically (through live guided training sessions conducted online, with the same design, frequency, and dosage of exercise).


No Intervention: Conventional management
Patients with conventional management and physical activity recommendation



Primary Outcome Measures :
  1. Change in left ventricular systolic function quantified by left ventricular ejection fraction and global longitudinal strain by transthoracic echocardiography [ Time Frame: 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 ]
    Fall of 10 absolute percentage points of left ventricular ejection fraction with final value below 53% or global longitudinal strain fall >15% with respect to baseline


Secondary Outcome Measures :
  1. Change in health-related quality of life assessed by the Functional Assessment of Cancer Therapy - Breast plus Arm Morbidity (FACT-B+4) questionnaire [ Time Frame: Baseline and at the end of the study at an average of 18 months ]
    Score achieved in the Functional Assessment of Cancer Therapy - Breast plus Arm Morbidity (FACT-B+4) questionnaire, a specific validated scale to assess quality of life of women with breast cancer. It comprises 27 items within 5 areas of assessment: physical well-being (7 items), social and family environment (7 items), emotional well-being (7 items), functional well-being (6 items) and worries related to the diagnosis and treatment of the disease (9 items). Each item is scored by means of a Likert scale from 0 to 5, with higher scores representing better results. The total score is obtained by adding the scores for each item, and ranges from a minimum of 0 (worst posible result) to a maximum of 146 (best possible result).

  2. Change in tolerance to chemotherapy: number of participants with significant cardiovascular and non-cardiovascular adverse effects throughout the study [ Time Frame: Every 3 months during study completion and at the end of the study at an average of 18 months ]
    Significant cardiovascular and non-cardiovascular adverse effects during treatment, threatening life, requiring admission, prolonging hospitalization, being clinically relevant or causing chemotherapy interruptions

  3. Change in global functional capacity assessed by conventional ergometry, cardiopulmonary exercise testing (CPET) or the 6-minute walking test (6MWT). [ Time Frame: Baseline and at the end of the study at an average of 18 months ]

    Change in functional capacity assessed by conventional ergometry, cardiopulmonary exercise test or the 6-minute walking test (6MWT) (metabolic equivalents: METs or peak oxygen consumption: VO2) * .

    *Due to COVID-19 pandemic, participants' assessment with CPET had to be stopped for safety concerns. In such cases, functional capacity was estimated from the maximum work rate in the 6-minute walking test (6MWT). This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes, which is well correlated with VO2. The 6MWT has been proved to be valid and reliable for functional capacity assessment in the study population.


  4. Change in localized lower limb functional capacity assessed by number of repetitions performed within 30 seconds in the sit-to-stand test [ Time Frame: Baseline and at the end of the study at an average of 18 months ]
    Number of repetitions in the sit-to-stand test within 30 seconds

  5. Change in shoulder functional capacity assessed by range of degrees in shoulder movement by goniometry [ Time Frame: Baseline and at the end of the study at an average of 18 months ]
    Range of degrees in shoulder movement measured by goniometry

  6. Change in upper limb strength measured by dynamometry (kg) [ Time Frame: Baseline and at the end of the study at an average of 18 months ]
    Kilograms by dynamometry of right and left upper limbs

  7. Change in shoulder pain and disability assessed by the SPADI (shoulder pain and disability index (SPADI) questionnaire [ Time Frame: Baseline and at the end of the study at an average of 18 months ]
    Score achieved in the SPADI (shoulder pain and disability index) questionnaire. The pain dimension consists of five questions regarding the severity of an individual's pain, functional activities are assessed with eight questions. Each question may be scored from 0 to 10. Verbal anchors for the pain dimension are 'no pain at all' (0) and 'worst pain imaginable' (10) ,and those for the functional activities are 'no difficulty' (0) and 'so difficult it required help' (10). The scores from both dimensions are averaged to produce a total score ranging from 0 (best) to 100 (worst).

  8. Change in cardiovascular risk profile as assessed by the presence or absence of classic cardiovascular risk factors [ Time Frame: Baseline and at the end of the study at an average of 18 months ]
    Dyslipidemia, Diabetes mellitus, Arterial Hypertension, Smoking status

  9. Change in anthropometric parameters: height in cm [ Time Frame: Baseline and at the end of the study at an average of 18 months ]
    Height measured in cm

  10. Change in anthropometric parameters: weight in kg [ Time Frame: Baseline and at the end of the study at an average of 18 months ]
    Weight measured in kg

  11. Change in anthropometric parameters: body mass index (BMI) in kg/m^2 [ Time Frame: Baseline and at the end of the study at an average of 18 months ]
    Weight and height will be combined to report BMI in kg/m^2

  12. Change in anthropometric parameters: abdominal circumference in cm [ Time Frame: Baseline and at the end of the study at an average of 18 months ]
    Abdominal perimeter measured with a tape measure in cm

  13. Change in resting heart rate measured by pulse oximetry (beats per min) [ Time Frame: Baseline and at the end of the study at an average of 18 months ]
    Resting heart rate by pulse oximetry (beats per min)

  14. Change in resting blood pressure (mmHg) measured by sphygmomanometer [ Time Frame: Baseline and at the end of the study at an average of 18 months ]
    Resting blood pressure by sphyngomanometer in mmHg

  15. Change in biomarkers NT-ProBNP [ Time Frame: Baseline and at the end of the study at an average of 18 months ]
    Value of NT-ProBNP(pg/mL) in blood tests

  16. Change in biomarkers: troponin [ Time Frame: Baseline and at the end of the study at an average of 18 months ]
    Value of troponin I (ng/mL) in blood tests

  17. Change in biomarkers: haemoglobin [ Time Frame: Baseline and at the end of the study at an average of 18 months ]
    Value of haemoglobin (g/dL) in blood tests

  18. Change in dietary pattern as assessed by the PREDIMED (PREvención con DIeta MEDiterránea) questionnaire [ Time Frame: Baseline and at the end of the study at an average of 18 months ]
    Validated questionnaire to assess adherence to Mediterranean diet, including 14 questions regarding dietary habits, rated with 0 or +1 points. Global score is calculated by summing points and ranges from 0 to 14, with higher score representing higher adherence.

  19. Change in the score for depression assessed by Zigmond and Snaith questionnaire to rate anxiety and depression [ Time Frame: 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 ]
    Score achieved in the depression subscale of the Zigmond and Snaith test for anxiety or depression, a self-applied questionnaire. Depression scale includes 7 items each, scored on Likert scale from 0 to 3. Global score ranges from 0 to 21, with higher scores representing greater depression. The authors suggest that scores higher than eleven would indicate "case" and more than eight would be considered "probable case" (Zigmond and Snaith, 1983).

  20. Change in the score for anxiety assessed by the Zigmond and Snaith questionnaire to rate depression and anxiety [ Time Frame: Baseline and at study completion, plus at the end of training (at an average of 12 to 15 months) in the intervention group ]
    Score achieved in the anxiety subscale of the Zigmond and Snaith test for anxiety or depression, a self-applied questionnaire. Anxiety scale includes 7 items each, scored on Likert scale from 0 to 3. Global score ranges from 0 to 21, with higher scores representing greater anxiety. The authors suggest that scores higher than eleven would indicate "case" and more than eight would be considered "probable case" (Zigmond and Snaith, 1983).

  21. Change in physical activity (minutes of dedicated physical activity) [ Time Frame: Baseline and at study completion at an average of 18 months ]
    Minutes of In- and out-of-hospital dedicated physical activity

  22. Change in physical activity assessed by the score in the Godin Leisure Test Exercise Questionnaire (GLTEQ) [ Time Frame: Baseline and at study completion at an average of 18 months ]
    Score achieved in the Godin Leisure Test Exercise Questionnaire (GLTEQ) for quantification of physical activity. Activities are classified into three subgroups: "strenuous," "moderate," and "light." The scores corresponding to the energy expenditure (metabolic equivalent (MET)) are obtained by multiplying activities performed for more than 15 min in a week with their coefficients. The numbers represent the MET intensity values (strenuous/ exhausting exercises: 9 METs, moderate exercises: 5 METs, and light exercises: 3 METs).The increasing scores are associated with the increasing number of exercise behaviors, providing references about the contribution of physical activity to health: the activity score of 24 units and more as active (substantial benefits); the activity score of 14-23 units as moderately active (some benefits); and the activity score of 13 units and less as inactive (less substantial or low benefits).

  23. Change in lymphedema assessed by perimeter of the upper limb by cirtometry (cm), stage and grade [ Time Frame: Baseline after surgery and 2-4 weeks after the end of chemotherapy (at an average of 12 to 15 months) ]
    Perimeter of the upper limb by cirtometry (cm), stage and grade as defined by the Spanish Society of Rehabilitation and Physical Medicine


Other Outcome Measures:
  1. Adherence and compliance to cardiac rehabilitation program (intervention group) assessed by number of training sessions attended/ number of sessions planned [ Time Frame: At the end of the cardiac rehabilitation program at an average of 12 to 15 months ]
    Number of training sessions attended / number of sessions planned

  2. Security of the cardiac rehabilitation program assessed by number of adverse events during training (intervention group) [ Time Frame: At the end of the cardiac rehabilitation program at an average of 12 to 15 months ]
    Adverse events during training

  3. Changes in expectations regarding the cardiac rehabilitation program assessed by a questionnaire (intervention group) [ Time Frame: Baseline and at the end of the cardiac rehabilitation program at an average of 12 to 15 months ]
    Program-related expectations at baseline and at the end of the program' are collected through an open question "What do you expect to achieve by participating in the program?" Responses regarding expectations will be categorized by the evaluator within the following areas: psychological sphere and/or social sphere and/or physical sphere. Global expectations of benefit are scored from 0 (no benefit) to 10 (highest benefit).

  4. Satisfaction with the cardiac rehabilitation program assessed by a questionnaire (intervention group) [ Time Frame: At the end of the cardiac rehabilitation program at an average of 12 to 15 months ]

    Satisfaction at the end of the program is assessed by a questionnaire including 9 questions concerning comfort with training sessions, training spaces and development of the program, which are scored from 0 (worse posible result) to 10 (best posible result). Total score is calculated by adding for each question, and ranges from 0 to 90.

    * Due to the introduction of telematic exercise training during COVID-19 pandemic, questions were slightly modified to include assessment of satisfaction with this training modality.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 69 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03964142


Contacts
Layout table for location contacts
Contact: Carlos Peña Gil, MD, PhD +34 981 950 778 carlos.pena.gil@sergas.es
Contact: Violeta González Salvado, MD +34 981 950 778 violeta.gonzalez.salvado@sergas.es

Locations
Layout table for location information
Spain
Hospital Clínico Universitario de Santiago Recruiting
Santiago de Compostela, A Coruña, Spain, 15706
Contact: Carlos Peña Gil, MD, PhD    +34 981 950 778    carlos.pena.gil@sergas.es   
Contact: Violeta González Salvado, MD    +34 981 950 778    violeta.gonzalez.salvado@sergas.es   
Hospital Universitari Vall d'Hebron Withdrawn
Barcelona, Spain, 08035
Sponsors and Collaborators
Hospital Clinico Universitario de Santiago
Instituto de Salud Carlos III
Investigators
Layout table for investigator information
Principal Investigator: Amparo Martínez Monzonís, MD, PhD Cardiology Department, Hospital Clínico Universitario de Santiago, CIBER-CV
Principal Investigator: Carlos Peña Gil, MD, PhD Cardiology Department, Hospital Clínico Universitario de Santiago, CIBER-CV
Study Director: José Ramón González Juanatey, MD, PhD Cardiology Department, Hospital Clínico Universitario de Santiago, CIBER-CV
Layout table for additonal information
Responsible Party: Carlos Peña Gil, Head of the Cardiac Rehabilitation Unit, Cardiology Department, Hospital Clinico Universitario de Santiago
ClinicalTrials.gov Identifier: NCT03964142    
Other Study ID Numbers: PI17/01687
First Posted: May 28, 2019    Key Record Dates
Last Update Posted: October 6, 2020
Last Verified: October 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Carlos Peña Gil, Hospital Clinico Universitario de Santiago:
Chemotherapy
Anthracyclines
Trastuzumab
Pertuzumab
Antibodies, Monoclonal, Humanized
Breast Cancer
Exercise therapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Cardiotoxicity
Pathologic Processes
Drug-Related Side Effects and Adverse Reactions
Chemically-Induced Disorders
Radiation Injuries
Wounds and Injuries