Stage I-IV Breast Cancer (Neo-adjuvant, Adjuvant, Locally Advanced and Metastatic)NCT01022086
Assessment of Cardiotoxicity by Cardiac Magnetic Resonance (CMR) in Breast Cancer Patients Receiving Trastuzumab
An observational study of Stage I-IV Breast Cancer (Neo-adjuvant, Adjuvant, Locally Advanced and Metastatic), run by Unity Health Toronto at 2 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage I-IV Breast Cancer (Neo-adjuvant, Adjuvant, Locally Advanced and Metastatic)
- What is being tested?
- Cardiac MRI and Biomarker Testing
- Type of treatment
- Surgery or procedure
- How many people
- 50 participants
- Where
- 2 sitesCanada
- Study dates
- Nov 2009to Dec 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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)
Who cannot join
- 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)
Trial locations and contacts
2 sites in 1 country.
Canada2 sites, 2 recruiting
- Recruiting
Odette Cancer Centre/Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
Teresa Petrella, BSc, MD, MSc, FRCPC, 416-480-5248, Teresa.Petrella@sunnybrook.ca
Kim Connelly, MD FRCPC, FACC, +14168645201, connellyk@smh.ca
- Recruiting
St. Michael's Hospital
Toronto, Ontario, M5B 1W8
Christine B Brezden-Masley, MD, PhD, 1-416-864-5734, brezdenc@smh.ca
Daisy Dastur, MHSc. CCRP, CCRC, 1-416-864-5354, dasturd@smh.ca
About this study
Official title: Assessment of Cardiotoxicity by Cardiac MRI Versus MUGA Scans in Breast Cancer Patients Receiving Trastuzumab: A Double-Blinded Prospective Observational Pilot Study
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.
Read the 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.
- Being tested
- Cardiac MRI, Biomarker Testing
- Keywords
- Breast Cancer, Cardiotoxicity, Trastuzumab, Cardiac MRI
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis, Cardiotoxicity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cardiac MRIProcedure or surgery
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 TestingBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Procedure: Cardiac MRI; Biological: Biomarker Testing | |
| 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). Receives: Procedure: Cardiac MRI; Biological: Biomarker Testing | |
| 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). Receives: Procedure: Cardiac MRI; Biological: Biomarker Testing | |
| 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). Receives: Procedure: Cardiac MRI; Biological: Biomarker Testing | |
| 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). Receives: Procedure: Cardiac MRI; Biological: Biomarker Testing |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare CMR with MUGA scans for determining LVEF and LV volumes in breast cancer patients treated with trastuzumab.
Measured: 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.
Measured: Five years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2009 (estimated)
- Study startNov 2009
- Primary completionDec 2019 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Stage I-IV Breast Cancer (Neo-adjuvant, Adjuvant, Locally Advanced and Metastatic)Studies of the same condition, open and under way.
- More trials run by Unity Health TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Unity Health Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01022086
- Sponsor's protocol ID
- Cardiac CMR
- Status last verified
- Jul 2017
- First submitted
- 27 Nov 2009
- Last updated
- 12 Jul 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 30390170Barthur 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.
PubMed 28395671
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Cardiotoxicity by Cardiac MRI Versus MUGA Scans in Breast Cancer Patients Receiving Trastuzumab: A Double-Blinded Prospective Observational Pilot Study
- ClinicalTrials.gov ID
- NCT01022086
- Acronym / sponsor ID
- Cardiac CMR
- Keywords
- Breast Cancer, Cardiotoxicity, Trastuzumab, Cardiac MRI
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Unity Health TorontoUniversity, hospital or other
- Collaborators
- Hoffmann-La Roche
- Study start
- Nov 2009
- Primary completion
- Dec 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 1 Dec 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| early stage/adjuvant | – | Procedure: Cardiac MRI, Biological: Biomarker TestingAnalyses 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 | – | Procedure: Cardiac MRI, Biological: Biomarker TestingAnalyses 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 | – | Procedure: Cardiac MRI, Biological: Biomarker TestingAnalyses 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 | – | Procedure: Cardiac MRI, Biological: Biomarker TestingAnalyses 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 | – | Procedure: Cardiac MRI, Biological: Biomarker TestingAnalyses 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cardiac MRICardiac 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. | Procedure or surgery | anthracycline-containing, early stage/adjuvant, locally advanced/neoadjuvant, metastatic, non-anthracycline containing |
| Biomarker TestingIn 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. | Biological | anthracycline-containing, early stage/adjuvant, locally advanced/neoadjuvant, metastatic, non-anthracycline containing |
Primary outcome
To compare CMR with MUGA scans for determining LVEF and LV volumes in breast cancer patients treated with trastuzumab.
Time frame: Five years
1 secondary outcome
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.
Time frame: Five years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2017.
- Derived from this study: PubMed 30390170Gong 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.
- Derived from this study: PubMed 28395671Barthur 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Stage I-IV Breast Cancer (Neo-adjuvant, Adjuvant, Locally Advanced and Metastatic), run by Unity Health Toronto at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Christine B Brezden-Masley, MD, PhD (1-416-864-5734, brezdenc@smh.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To compare CMR with MUGA scans for determining LVEF and LV volumes in breast cancer patients treated with trastuzumab. (time frame: Five years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01022086, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2017.