Assessment of Cardiotoxicity by Cardiac Magnetic Resonance (CMR) in Breast Cancer Patients Receiving Trastuzumab

NCT ID: NCT01022086

Last Updated: 2017-07-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

50 participants

Study Classification

OBSERVATIONAL

Study Start Date

2009-11-30

Study Completion Date

2019-12-31

Brief Summary

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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.

Detailed Description

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Currently, serial MUGA scans are the imaging modality of choice for monitoring cardiotoxicity. However, MUGA scans only measure LVEF at the cost of ionizing radiation and considerable inter-study variability, and do not reliably detect cardiomyopathy. CMR is a highly accurate technique and represents a promising imaging alternative. Because CMR is now considered the gold standard for measuring LVEF and subclinical alterations in cardiac structure and function, it will be used in this prospective observational pilot study to determine its effectiveness for monitoring cardiotoxicity in patients receiving trastuzumab. Serial CMR will be compared to serial MUGA scans, as they are routinely used for LVEF monitoring with trastuzumab therapy, in standard practice. Cardiac biomarkers will also be measured in relation to CMR and MUGA scans. Furthermore, we will determine the long-term clinical and prognostic implications of trastuzumab-induced cardiotoxicity detected by these various methods.

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 trastuzumab.

Conditions

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Stage I-IV Breast Cancer (Neo-adjuvant, Adjuvant, Locally Advanced and Metastatic)

Study Design

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Observational Model Type

OTHER

Study Time Perspective

PROSPECTIVE

Study Groups

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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).

Cardiac MRI

Intervention Type PROCEDURE

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.

Biomarker Testing

Intervention Type BIOLOGICAL

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.

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).

Cardiac MRI

Intervention Type PROCEDURE

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.

Biomarker Testing

Intervention Type BIOLOGICAL

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.

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).

Cardiac MRI

Intervention Type PROCEDURE

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.

Biomarker Testing

Intervention Type BIOLOGICAL

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.

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).

Cardiac MRI

Intervention Type PROCEDURE

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.

Biomarker Testing

Intervention Type BIOLOGICAL

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.

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).

Cardiac MRI

Intervention Type PROCEDURE

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.

Biomarker Testing

Intervention Type BIOLOGICAL

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.

Interventions

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Cardiac MRI

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.

Intervention Type PROCEDURE

Biomarker Testing

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.

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* 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)

Exclusion Criteria

* 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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role collaborator

Unity Health Toronto

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Odette Cancer Centre/Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Site Status RECRUITING

St. Michael's Hospital

Toronto, Ontario, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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Christine B Brezden-Masley, MD, PhD

Role: CONTACT

1-416-864-5734

Daisy Dastur, MHSc, CCRP, CCRC

Role: CONTACT

1-416-864-5354

Facility Contacts

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Teresa Petrella, BSc, MD, MSc, FRCPC

Role: primary

416-480-5248

Kim Connelly, MD FRCPC, FACC

Role: backup

+14168645201

Christine B Brezden-Masley, MD, PhD

Role: primary

1-416-864-5734

Daisy Dastur, MHSc. CCRP, CCRC

Role: backup

1-416-864-5354

References

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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.

Reference Type DERIVED
PMID: 30390170 (View on PubMed)

Barthur 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.

Reference Type DERIVED
PMID: 28395671 (View on PubMed)

Other Identifiers

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Cardiac CMR

Identifier Type: -

Identifier Source: org_study_id

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