Assessment of Cardiotoxicity by Cardiac Magnetic Resonance (CMR) in Breast Cancer Patients Receiving Trastuzumab
1 other identifier
observational
50
1 country
2
Brief Summary
Herceptin has shown significant improvement in breast cancer therapy and improved survival of patients over-expressing the HER-2 protein by 50%. However, Herceptin has shown to negatively affect the heart, and frequent heart monitoring with multiple gated acquisition (MUGA) scans is required. MUGA scans use radiation and are not very accurate. This study will use cardiac magnetic resonance images (CMRs) to evaluate heart function and compare to MUGA scans in patients receiving Herceptin for early-stage breast cancer. In addition, novel biomarkers will also be assessed at the same time to help identify possible patients at risk for developing heart toxicities.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for all trials
Started Nov 2009
Longer than P75 for all trials
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 1, 2009
CompletedFirst Submitted
Initial submission to the registry
November 27, 2009
CompletedFirst Posted
Study publicly available on registry
December 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2019
CompletedJuly 12, 2017
July 1, 2017
10.1 years
November 27, 2009
July 11, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To compare CMR with MUGA scans for determining LVEF and LV volumes in breast cancer patients treated with trastuzumab.
Five years
Secondary Outcomes (1)
To examine the association between changes in biomarker levels and changes in cardiac structure and function as measured by CMR in breast cancer patients receiving trastuzumab.
Five years
Other Outcomes (1)
To determine the long-term prognostic significance of reduced LVEF and myocardial injury detected by CMR and biomarkers in breast cancer patients treated with trastuzumab.
Five years
Study Arms (5)
early stage/adjuvant
Analyses will also be stratified according to the patient's stage of disease (i.e. early stage/adjuvant, locally advanced/neoadjuvant, and metastatic) and type of chemotherapy regimen (i.e. anthracycline-containing vs. non-anthracycline).
locally advanced/neoadjuvant
Analyses will also be stratified according to the patient's stage of disease (i.e. early stage/adjuvant, locally advanced/neoadjuvant, and metastatic) and type of chemotherapy regimen (i.e. anthracycline-containing vs. non-anthracycline).
metastatic
Analyses will also be stratified according to the patient's stage of disease (i.e. early stage/adjuvant, locally advanced/neoadjuvant, and metastatic) and type of chemotherapy regimen (i.e. anthracycline-containing vs. non-anthracycline).
anthracycline-containing
Analyses will also be stratified according to the patient's stage of disease (i.e. early stage/adjuvant, locally advanced/neoadjuvant, and metastatic) and type of chemotherapy regimen (i.e. anthracycline-containing vs. non-anthracycline).
non-anthracycline containing
Analyses will also be stratified according to the patient's stage of disease (i.e. early stage/adjuvant, locally advanced/neoadjuvant, and metastatic) and type of chemotherapy regimen (i.e. anthracycline-containing vs. non-anthracycline).
Interventions
Cardiac magnetic resonance (CMR) imaging, otherwise called a cardiac (heart) MRI is a safe and standard clinical test that creates detailed images of your heart. It uses a computer to create images of your heart as it is beating, producing both still and moving pictures of your heart and major blood vessels. This test will allow the health professionals to obtain images of your beating heart and to look at the structure and function. Cardiac MRIs can help diagnose and evaluate a number of diseases conditions (such as heart failure, and heart valve disease) and will help doctors decide how to treat or manage patients who have heart problems.
In addition to undergoing CMR imaging, patients will also have blood tests for two proteins, which serve as markers of heart injury and heart failure. These are called BNP and Troponin. These blood tests are currently used in clinical practice, but their precise role in monitoring heart function in cancer patients has not been well studied. Since the precise cause of Trastuzumab-induced heart damage is currently unknown, it is hoped that these two blood markers will provide valuable insights into how this happens. Peripheral venous blood samples will also be drawn at each CMR time-point. TGF β1, amino terminal propeptide of procollagen type I (PINP) and type III (PIIINP) and the carboxy-terminal telopeptide of collagen type 1 (CITP) will be measured by radioimmunoassay.
Eligibility Criteria
This will be a double-blinded prospective observational pilot study of breast cancer patients with overexpression of HER2 on breast pathology (using either immunohistochemistry \[IHC\] and/or fluorescence in-situ hybridization \[FISH\]), who have never received trastuzumab before, who will be treated with chemotherapy (as per standard of care) and trastuzumab. Target recruitment number will be 50 patients over 18-24 months. Systemic therapy will include chemotherapy as dictated by Cancer Care Ontario's systemic therapy practice guidelines for stage I-IV (i.e. early stage, locally advanced and metastatic) breast cancer patients with HER2 overexpression.
You may qualify if:
- Aged 18 years or older
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Histologically confirmed diagnosis of invasive breast carcinoma
- Histologically confirmed HER2 overexpression using IHC and/or FISH and/or DISH
- Planned treatment with Trastuzumab or TDM-1
- Baseline LVEF \>50% by MUGA (ECHOs or any other type of cardiac scanning may be done as part of standard clinical care, at the investigator's discretion; ECHOs cannot be done in place of MUGA scans)
You may not qualify if:
- Previous treatment with trastuzumab or any other anti-HER2 agent (e.g. lapatinib, pertuzumab, etc.)
- Pre-existing symptomatic Heart Failure (NYHA Class III or IV)
- Recent acute coronary syndrome (myocardial infarction, unstable angina) within the last six months
- Recent coronary revascularization (percutaneous coronary intervention or coronary bypass surgery) within six months
- Permanent atrial fibrillation
- Inability to undergo MRI (shrapnel, metallic implants/clips, pacemaker or defibrillator)
- Currently pregnant and/or nursing
- Planned or current use of other targeted biological therapies that can potentially cause cardiotoxicity (i.e. bevacizumab)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Unity Health Torontolead
- Hoffmann-La Rochecollaborator
Study Sites (2)
Odette Cancer Centre/Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5, Canada
St. Michael's Hospital
Toronto, Ontario, M5B 1W8, Canada
Related Publications (2)
Gong IY, Ong G, Brezden-Masley C, Dhir V, Deva DP, Chan KKW, Graham JJ, Chow CM, Thavendiranathan P, Dai D, Ng MY, Barfett JJ, Connelly KA, Yan AT. Early diastolic strain rate measurements by cardiac MRI in breast cancer patients treated with trastuzumab: a longitudinal study. Int J Cardiovasc Imaging. 2019 Apr;35(4):653-662. doi: 10.1007/s10554-018-1482-2. Epub 2018 Nov 2.
PMID: 30390170DERIVEDBarthur A, Brezden-Masley C, Connelly KA, Dhir V, Chan KK, Haq R, Kirpalani A, Barfett JJ, Jimenez-Juan L, Karur GR, Deva DP, Yan AT. Longitudinal assessment of right ventricular structure and function by cardiovascular magnetic resonance in breast cancer patients treated with trastuzumab: a prospective observational study. J Cardiovasc Magn Reson. 2017 Apr 10;19(1):44. doi: 10.1186/s12968-017-0356-4.
PMID: 28395671DERIVED
Biospecimen
Mandatory: Troponin I/T and BNP will be assessed at each CMR time-point (and measured as per the institution's standard biochemistry laboratory commercial assay techniques. Optional: For consenting patients only, peripheral venous blood samples will be drawn at each CMR time-point. Each sample will be obtained with a tourniquet free technique, then undergo centrifugation to prevent platelet degranulation and enable platelet free serum to be obtained. Serum will then be separated and stored at -800C for subsequent analysis. TGF β1, amino terminal propeptide of procollagen type I (PINP) and type III (PIIINP) and the carboxyterminal telopeptide of collagen type 1 (CITP) will be measured by radioimmunoassay with commercially available kits. The intra-assay variations for determining PINP, PIINP, and CITP are 7%, 5%, and 8% respectively. CITP will be measured by ELISA according to the manufacturer's instructions.
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- OTHER
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 27, 2009
First Posted
December 1, 2009
Study Start
November 1, 2009
Primary Completion
December 1, 2019
Study Completion
December 1, 2019
Last Updated
July 12, 2017
Record last verified: 2017-07