Evaluation of Myocardial Changes During BReast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI (EMBRACE-MRI)

February 12, 2023 updated by: University Health Network, Toronto

Evaluation of Myocardial Changes During BReast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI - The EMBRACE MRI Study

Breast cancer is the most common cancer amongst Canadian women. 15-20% of early breast cancers have high levels of a protein called HER2 which is associated with worse survival. Treatment of these patients with anthracyclines followed by trastuzumab (which targets HER2) improves survival. Unfortunately, these medications together can cause heart muscle injury resulting in heart dysfunction or failure in about 14% and 3.6% of the patients, respectively. Once heart failure (HF) occurs, about 60% of patients will not live past 2 years. Studies have suggested that patients with heart injury caused by anthracyclines may be more likely to develop HF with addition of trastuzumab. Therefore tests to find early heart injury after anthracyclines may allow doctors to start heart protective medications with the hope of preventing HF. Also, animal and small patient studies have shown that an increase in the water levels of the heart muscle (edema) may be an early sign of heart injury from anthracyclines. Cardiac MRI is a unique technique that has been shown to detect edema in various heart diseases.

The investigators will test the theory that, in women receiving treatment for breast cancer, heart edema detected by MRI at the end of anthracyclines will identify patients who will later develop heart dysfunction. MRI studies with novel techniques will be done pre-therapy, after anthracyclines, during herceptin, and at end of all therapy. The investigators will compare patients with and without heart dysfunction to test if patients with heart dysfunction are more likely to have edema after anthracyclines. Ultimately the investigators hope to use cardiac MRI to identify high risk patients and study various heart protective medications to prevent HF. This will improve the personal health of cancer patients by allowing them to live free of heart disease after their cancer therapy. Ultimately at a population level this will allow doctors to provide care that can be uniquely designed for each patient based on their individual risk.

The first 136 patients enrolled are included in the first part of the study, named EMBRACE-MRI 1. Enrollment for this part of the study is complete.

The remaining 44 patients will be enrolled into EMBRACE-MRI 2, which includes slight differences in obtaining sequences in MRI imaging.

Study Overview

Status

Active, not recruiting

Conditions

Study Type

Observational

Enrollment (Anticipated)

180

Contacts and Locations

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

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2N2
        • Toronto General Hospital

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

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

Women ≥18 years with stage I-III, HER2+ breast cancer

Description

Inclusion Criteria:

  • Scheduled to undergo treatment with one of the following regimens: (a) 5-fluorouracil, epirubicin, cyclophosphamide, followed by docetaxel and trastuzumab, (b) adriamycin, cyclophosphamide, followed by docetaxel and trastuzumab, (c) adriamycin-cyclophosphamide with weekly paclitaxel and trastuzumab, or (d) dose dense adriamycin and cyclophosphamide followed by dose dense paclitaxel and trastuzumab
  • Able to tolerate five ~60 minute CMR examinations over 15 months
  • Able to give informed consent

Exclusion Criteria:

  • Life expectancy < 12 months
  • Participating in a clinical trial of a new cancer drug
  • Having received previous anthracycline
  • History of myocardial infarction or previous heart failure
  • Current unstable angina, persistent atrial fibrillation or other irregular rhythm, or a history of more than mild regurgitant or stenotic valvular heart disease
  • Severely reduced renal function (GFR ≤ 30 milliliters/minute)
  • General MRI contraindications
  • Baseline LVEF <55% by echo
  • echocardiography image quality inadequate for strain analysis

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The presence of myocardial edema stratified by the presence or absence of conventionally defined cardiotoxicity (this is a binary outcome).
Time Frame: 2-15 months
Myocardial edema is defined as an 8% increase in segmental T2 values measured in milliseconds in at least 2 myocardial segments at either of the 2 early time points. Cardiotoxicity is defined as Cardiac Magnetic Resonance Imaging (CMR) measured (1) ≥5% absolute reduction in Left Ventricular Ejection Fraction (LVEF) from baseline to an LVEF <55% with signs or symptoms of HF, OR (2) a ≥10% absolute reduction in LVEF from baseline to <55% without accompanying signs or symptoms at the time points when CMR is obtained OR (3) the same amount of reduction in LVEF as above, identified by echo at any time point (done every 3 months) and confirmed by CMR at that time.
2-15 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The presence of edema stratified by the presence or absence of any drop in LVEF ≥5% by CMR by end of therapy (this is a binary outcome).
Time Frame: 2-15 months
Please see definition for edema above
2-15 months

Collaborators and Investigators

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

Sponsor

University Health Network, Toronto

Collaborators

Canadian Institutes of Health Research (CIHR)
University of Toronto

Investigators

  • Principal Investigator: Paaladinesh Thavendiranathan, MD, University Health Network, Toronto
  • Principal Investigator: Bernd Wintersperger, MD, University Health Network, Toronto

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 (ACTUAL)

October 1, 2013

Primary Completion (ANTICIPATED)

August 1, 2024

Study Completion (ANTICIPATED)

January 1, 2027

Study Registration Dates

First Submitted

November 11, 2014

First Submitted That Met QC Criteria

December 2, 2014

First Posted (ESTIMATE)

December 3, 2014

Study Record Updates

Last Update Posted (ESTIMATE)

February 14, 2023

Last Update Submitted That Met QC Criteria

February 12, 2023

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 13-6543C

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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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