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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by St. Michael's Hospital, Toronto
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
Christine Brezden-Masley, St. Michael's Hospital, Toronto
ClinicalTrials.gov Identifier:
NCT01022086
First received: November 27, 2009
Last updated: January 11, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention
Stage I-IV Breast Cancer (Neo-adjuvant, Adjuvant, Locally Advanced and Metastatic)
Procedure: Cardiac MRI
Biological: Biomarker Testing

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Assessment of Cardiotoxicity by Cardiac MRI Versus MUGA Scans in Breast Cancer Patients Receiving Trastuzumab: A Double-Blinded Prospective Observational Pilot Study

Resource links provided by NLM:


Further study details as provided by St. Michael's Hospital, Toronto:

Primary Outcome Measures:
  • To compare CMR with MUGA scans for determining LVEF and LV volumes in breast cancer patients treated with trastuzumab. [ Time Frame: five years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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.

Other Outcome Measures:
  • 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.

Biospecimen Retention:   Samples Without DNA

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.


Estimated Enrollment: 50
Study Start Date: November 2009
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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).
Procedure: 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.
Biological: 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.

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).
Procedure: 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.
Biological: 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.

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).
Procedure: 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.
Biological: 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.

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).
Procedure: 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.
Biological: 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.

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).
Procedure: 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.
Biological: 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.


Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

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.

Criteria

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)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01022086

Contacts
Contact: Christine B Brezden-Masley, MD, PhD 1-416-864-5734 brezdenc@smh.ca
Contact: Daisy Dastur, MHSc, CCRP, CCRC 1-416-864-5354 dasturd@smh.ca

Locations
Canada, Ontario
Odette Cancer Centre/Sunnybrook Health Sciences Centre Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Teresa Petrella, BSc, MD, MSc, FRCPC    416-480-5248    Teresa.Petrella@sunnybrook.ca   
Contact: Kim Connelly, MD FRCPC, FACC    +14168645201    connellyk@smh.ca   
Sub-Investigator: Kim Connelly, MD FRCPC, FACC         
Principal Investigator: Teresa Petrella, MD, MSc, FRCPC         
Sub-Investigator: Shaheeda Ahmed,, MD, FRCPC         
Sub-Investigator: Kelvin Chan,, MD, FRCPC         
Sub-Investigator: Maureen E Trudeau, MA, MD, FRCPC         
Sub-Investigator: Sunil Verma, MD         
St. Michael's Hospital Recruiting
Toronto, Ontario, Canada, M5B 1W8
Contact: Christine B Brezden-Masley, MD, PhD    1-416-864-5734    brezdenc@smh.ca   
Contact: Daisy Dastur, MHSc. CCRP, CCRC    1-416-864-5354    dasturd@smh.ca   
Principal Investigator: Christine B Brezden-Masley, MD, PhD         
Sub-Investigator: Rashida Haq, MD         
Sub-Investigator: Anish Kripalani, MD         
Sub-Investigator: Andrew Yan, MD         
Sub-Investigator: Kim Connelly, MD FRCPC, FACC         
Sub-Investigator: Rosane Nisembaum, PhD         
Sub-Investigator: Suzanne Richter, MSc., MD, FRCPC         
Sponsors and Collaborators
Christine Brezden-Masley
Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Christine Brezden-Masley, Head, Oncology Clinical Research Group; Division Head, Department of Hematrology/Oncology, St. Michael's Hospital, Toronto
ClinicalTrials.gov Identifier: NCT01022086     History of Changes
Other Study ID Numbers: Cardiac CMR
Study First Received: November 27, 2009
Last Updated: January 11, 2013
Health Authority: Canada: Canadian Institutes of Health Research

Keywords provided by St. Michael's Hospital, Toronto:
Breast Cancer
Cardiotoxicity
Trastuzumab
Cardiac MRI

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Trastuzumab
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014