Clinical trial NCT01022086: Assessment of Cardiotoxicity by Cardiac Magnetic Resonance (CMR) in Breast Cancer Patients Receiving Trastuzumab
Official title: Assessment of Cardiotoxicity by Cardiac MRI Versus MUGA Scans in Breast Cancer Patients Receiving Trastuzumab: A Double-Blinded Prospective Observational Pilot Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Stage I-IV Breast Cancer (Neo-adjuvant, Adjuvant, Locally Advanced and Metastatic)
Keywords: Breast Cancer
Cardiotoxicity
Trastuzumab
Cardiac MRI
Lead sponsor: Unity Health Toronto
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
First posted: 2009-12-01
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
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.

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.

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 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)

Primary outcomes:
measure: To compare CMR with MUGA scans for determining LVEF and LV volumes in breast cancer patients treated with trastuzumab.
timeFrame: Five years
Secondary outcomes:
measure: 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.
timeFrame: Five years
Other outcomes:
measure: 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.
timeFrame: Five years
Locations:
city: Toronto
country: Canada
facility: Odette Cancer Centre/Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
Study officials:
References:
citation: 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.
citation: 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.