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Early Detection of Cardiovascular Changes After Radiotherapy for Breast Cancer (EARLY-HEART)

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ClinicalTrials.gov Identifier: NCT03297346
Recruitment Status : Recruiting
First Posted : September 29, 2017
Last Update Posted : June 19, 2018
Sponsor:
Collaborators:
Academisch Ziekenhuis Groningen
Technische Universität München
Institut Català d'Oncologia
Hospital de Santa Maria, Portugal
University of Paris 5 - Rene Descartes
Information provided by (Responsible Party):
Sophie JACOB, Institut de Radioprotection et de Surete Nucleaire

Brief Summary:

Breast cancer (BC) radiotherapy leads to coincidental radiation of the heart, resulting in increased risk of a variety of heart diseases. Identifying BC patients with the highest risk of radiation-induced cardiac complications is crucial for developing strategies for primary and secondary prevention. Little has been done on the relationship between dose distribution to different anatomical cardiac structures during radiotherapy and early cardiovascular changes that may lead to cardiac complications.

In the framework of the European project MEDIRAD, the EARLY-HEART multicenter prospective cohort was launched in August 2017, involving 5 investigating centers from France, Netherlands, Germany, Spain and Portugal. With 250 BC patients prospectively followed for 2 years, the main objective is to identify and validate the most important cardiac imaging (echocardiography, computed tomography coronary angiography, cardiac magnetic resonance imaging) and circulating biomarkers of radiation-induced cardiovascular changes arising in the first 2 years after BC radiotherapy.


Condition or disease Intervention/treatment Phase
Breast Cancer Female Other: Cardiac imaging and circulating biomarkers Not Applicable

Detailed Description:

EARLY-HEART is a multicentre prospective cohort study that will include 250 female primary breast cancer cases aged 40-75 years treated with postoperative radiotherapy (RT) alone after breast-conserving surgery using modern planning-CT based RT technologies and followed for 2 years after RT in one of the 5 participating hospitals. In addition to the standard follow-up, patients will need to give repeated blood samples and will undergo repeated cardiac imaging:

  • Functional and anatomical cardiac imaging biomarkers will be based on automated 2D-speckle-tracking echocardiography (ECHO-ST); Computed Tomography Coronary Angiography (CT) and cardiac magnetic resonance imaging (MRI).
  • Circulating biomarkers (BLOOD) will be based on a panel of multiple classical or novel blood-based biomarkers.

Imaging and circulating biomarkers measurements will be assessed at baseline before RT (ECHO, CT, MRI, BLOOD); at the end of RT (BLOOD); 6 months after RT (ECHO, MRI, BLOOD) and 24 months after RT (ECHO, CT, MRI, BLOOD).

Changes in functional and anatomical cardiac imaging and circulating biomarkers between unexposed status before RT and exposed status after RT at different time points will be first analysed to evaluate the effects of RT on the heart.

All relevant DICOM-data (including planning-CT scans and the ECHO, MRI and CT) will be centralized to the MEDIRAD-ENACT database managed by University of Groningen for automated segmentation of all cardiac substructures (including coronary arteries) to ensure uniformity of the segmentation procedure between centres. The RT planning CTs will be used to generate dose volume histograms and 3D dose maps of the heart and cardiac substructures in order to correlate the localization of any cardiovascular change with the anatomical dose distribution.

In the presence of a cardiac outcome, a multimetric Normal Tissue Complication Probability (NTCP) individual risk model will be constructed and an integrative clinical-biologic risk score will be developed for individual risk prediction.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Early Detection of Cardiovascular Changes After Radiotherapy for Breast Cancer (EARLY HEART Study) in the Frame of the Implications of MEDIcal Low Dose RADiation Exposure (MEDIRAD) European Project
Actual Study Start Date : September 1, 2017
Estimated Primary Completion Date : October 1, 2020
Estimated Study Completion Date : May 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Breast cancer patients treated with RT

Cardiac imaging and circulating biomarkers measurements to evaluate:

  • myocardial dysfunction and deformation (ECHO-ST)
  • coronary artery lesions and coronary artery calcium score (CT)
  • myocardium including tissue abnormalities, cardiac morphology and function (MRI)
  • blood-based biomarkers of cardiovascular changes (BLOOD)
Other: Cardiac imaging and circulating biomarkers
Automated 2D-speckle-tracking echocardiography (ECHO-ST); Computed tomography coronary angiography (CT); Cardiac magnetic resonance imaging (MRI); Blood samples for circulating biomarkers measurements (BLOOD)




Primary Outcome Measures :
  1. Number of patients with decreased myocardial function assessed by echocardiography [ Time Frame: 2 years after radiotherapy (baseline measurements performed before radiotherapy) ]
    Number of patients with an increased of at least 2.5% in the Global Longitudinal Strain (GLS) between baseline and 2 years after radiotherapy


Secondary Outcome Measures :
  1. Changes in myocardial function measurements assessed by echocardiography [ Time Frame: 6 months and 2 years after radiotherapy (baseline measurements performed before radiotherapy) ]
    Increase of the segmental strain measurements (unit of measures:%)

  2. Anatomical changes in coronary arteries assessed by cardiac CT [ Time Frame: 2 years after radiotherapy (baseline measurements performed before radiotherapy) ]
    Increase of the number of coronary segments containing any plaque or increase of the calcium score

  3. Myocardial tissue abnormalities assessed by cardiac MRI [ Time Frame: 6 months and 2 years after radiotherapy (baseline measurements performed before radiotherapy) ]
    Increase of the native mean myocardial T1 mapping value

  4. Changes in circulating biomarkers measurements [ Time Frame: at the end of radiotherapy (through radiotherapy completion, an average of 5 weeks after starting date of radiotherapy), 6 months and 2 years after radiotherapy (baseline measurements performed before radiotherapy) ]

    Significant increase or decrease in the following biomarkers:

    classical biomarkers of cardiac injury (C-reactive protein, Troponin I, Troponin T, B-type natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-Pro BNP), beta2-Microglobulin, Galectin 3); Inflammatory cytokines; biomarkers of endothelial activation and dysfunction; Microparticles; MicroRNAs; circulating DNA methylation




Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Female unilateral breast cancer patients
  • Treated with primary breast conserving surgery for stage I-III invasive adenocarcinoma of the breast or ductal carcinoma in situ (DCIS)
  • Age between 40-75 years at time of start radiotherapy
  • World Health Organisation (WHO) performance status 0-1
  • Planned for radiotherapy alone to the breast with or without the lymph node areas
  • Radiotherapy based on planning-CT scan using either three dimensional conformal radiation therapy (3D-CRT), Intensity-modulated radiotherapy (IMRT), or Volumetric Arc Therapy (VMAT/RapidArc)
  • Written Informed consent

Exclusion Criteria:

  • Male breast cancer patients
  • Neoadjuvant or adjuvant chemotherapy
  • M1 disease (metastatic breast cancer)
  • Medical history of coronary artery disease and/or myocardial infarction and/or atrial fibrillation
  • Previous thoracic or mediastinal radiation
  • Contraindications to injection of iodinated contrast such as allergy or renal failure
  • Pregnancy or lactation
  • Atrial fibrillation detected during electrocardiogram before radiotherapy
  • Abnormal echocardiography before radiotherapy defined as: Left Ventricular Ejection Fraction<50%; longitudinal strain ≤ -16%; longitudinal strain rate <-1%, and/or abnormal wall motion
  • Presence of myocardial infarction detected during MRI before radiotherapy
  • CT or MRI results before radiotherapy requiring revascularisation

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): NCT03297346


Contacts
Contact: Sophie Jacob, PhD +33561145608 sophie.jacob@irsn.fr

Locations
France
IRSN - Clinique Pasteur Recruiting
Toulouse, France
Contact: Sophie Jacob, PhD    +33561145608    sophie.jacob@irsn.fr   
Principal Investigator: Atul Pathak, Md, PhD         
Germany
Klinikum rechts der Isar der Technischen Universität München Not yet recruiting
Munich, Germany
Contact: Michael Mayinger, MD       michael.mayinger@tum.de   
Principal Investigator: Stephanie Combs, MD, PhD         
Netherlands
Academisch Ziekenhuis Groningen Recruiting
Groningen, Netherlands
Contact: Anne Crijns, MD, PhD    +31652724432    a.p.g.crijns@umcg.nl   
Principal Investigator: Anne Crijns, MD, PhD         
Portugal
Associação para Investigação e Desenvolvimento da Faculdade de Medicina Recruiting
Lisbon, Portugal
Contact: Constantino Susana, PhD       sconstantino@medicina.ulisboa.pt   
Principal Investigator: Manuela Fiuza, MD, PhD         
Spain
Institut Català d'Oncologia Recruiting
Girona, Spain
Contact: Arantxa Eraso, MD, PhD       aeraso@iconcologia.net   
Principal Investigator: Arantxa Eraso, MD, PhD         
Sponsors and Collaborators
Institut de Radioprotection et de Surete Nucleaire
Academisch Ziekenhuis Groningen
Technische Universität München
Institut Català d'Oncologia
Hospital de Santa Maria, Portugal
University of Paris 5 - Rene Descartes
Investigators
Study Chair: Sophie Jacob, PhD Institut de Radioprotection et de Sûreté Nucléaire
  Study Documents (Full-Text)

Documents provided by Sophie JACOB, Institut de Radioprotection et de Surete Nucleaire:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sophie JACOB, PhD, Institut de Radioprotection et de Surete Nucleaire
ClinicalTrials.gov Identifier: NCT03297346     History of Changes
Other Study ID Numbers: MEDIRAD EARLY-HEART_1.2
First Posted: September 29, 2017    Key Record Dates
Last Update Posted: June 19, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sophie JACOB, Institut de Radioprotection et de Surete Nucleaire:
radiotherapy
cardiovascular changes
cardiac imaging
circulating biomarkers
dosimetry

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases