Can an MRI scan show early signs of medication-related changes to the heart in patients with breast cancer treated with trastuzumab?

ISRCTN ISRCTN83167415
DOI https://doi.org/10.1186/ISRCTN83167415
Secondary identifying numbers HER2-CMR
Submission date
14/11/2018
Registration date
23/11/2018
Last edited
23/11/2018
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Injury, Occupational Diseases, Poisoning
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Background and study aims
Trastuzumab is a drug that targets oestrogen signalling and can be used to treat selected breast cancer patients. It has been shown to delay and prevent death from breast cancer. However, with more patients surviving breast cancer, it becomes more important to prevent side effects. Trastuzumab can lead to heart failure in up to a quarter of patients receiving this drug. In most cases this heart failure is reversible after trastuzumab treatment finishes. However, these patients have higher lifetime risk of heart problems such as chronic (long-lasting) heart failure, myocardial infarctions (heart attacks) or other forms of heart disease. Until now, the main way to prevent trastuzumab-associated heart failure is repeated screening using echocardiography (ultrasound scanning of the heart). It is possible that MRI scans of the heart might show the early signs of heart failure resulting from trastuzumab treatment long before symptoms occur. This study aims to compare heart MRI scans before, during and after trastuzumab therapy and to identify the MRI changes that best predict which patients will later develop trastuzumab-associated heart failure. Doing this we might be able to make trastuzumab therapy safer in the future.

Who can participate?
Adult patients with breast cancer who are expected to be treated with trastuzumab

What does the study involve?
All participants receive heart MRI scans before, during and after five treatments with trastuzumab. All participants receive treatment for their breast cancer as usual.

What are the possible benefits and risks of participating?
Participants might benefit from earlier detection of heart problems using MRI compared to ultrasound. During the MRI scan, participants receive a standard dose of contrast medium that in rare occasions can cause allergic reactions. However, there are no study-associated side effects that exceed those of a regular MRI scan.

Where is the study run from?
HELIOS Hospital Berlin-Buch (Germany)

When is the study starting and how long is it expected to run for?
June 2018 to December 2020

Who is funding the study?
The cost of this study will be funded by the research group itself through university-affiliated research grants. No external funding is needed.

Who is the main contact?
Dr Fabian Muehlberg
Fabian.muehlberg@helios-gesundheit.de

Contact information

Dr Fabian Muehlberg
Scientific

HELIOS Hospital Berlin-Buch/Working group Cardiac MRI
Schwanebecker Chaussee 50
Berlin
13125
Germany

ORCiD logoORCID ID 0000-0002-7981-5178

Study information

Study designObservational cohort study
Primary study designObservational
Secondary study designCohort study
Study setting(s)Hospital
Study typeDiagnostic
Participant information sheet Not available in web format, please use contact details to request a participant information sheet.
Scientific titlePrediction of trastuzumab-associated cardiomyopathy using cardiovascular MRI
Study acronymHER2-CMR
Study objectivesTrastuzumab is known to be induced reversible and irreversibly congestive heart failure. We hypothesized that cardiac MRI is able to detect early changes in the myocardial structure after the first application of trastuzumab but long before clinical signs of heart failure occur. In detail, we hypothesized that myocardial T1 times change very early after start of trastuzumab.
Ethics approval(s)Charité University Medicine Berlin Ethics Board (Campus Mitte), 23/10/2018, ref: EA1/176/18
Health condition(s) or problem(s) studiedTrastuzumab-associated cardiomyopathy
InterventionParticipants receive a maximum of four cardiac MRIs. One MRI before start of chemotherapy (which typically happens before start of trastuzumab), one MRI directly before start of trastuzumab, one MRI directly before the second administration of trastuzumab and one MRI after 5 cycles of trastuzumab.
Intervention typeDevice
Pharmaceutical study type(s)
Phase
Drug / device / biological / vaccine name(s)
Primary outcome measureMean native myocardial T1 time measured using MRI (MOLLI sequences) at all time points (before start of chemotherapy, before the first dose of trastuzumab, before the second dose of trastuzumab and after 5 cycles of trastuzumab)
Secondary outcome measures1. Left ventricular ejection fraction
2. Myocardial T2 time
3. Late gadolinium enhancement
4. Longitudinal strain
5. Circumferential strain
All secondary outcome measures are assessed using MRI at all time points (before start of chemotherapy, before the first dose of trastuzumab, before the second dose of trastuzumab and after 5 cycles of trastuzumab).
Overall study start date01/06/2018
Completion date31/12/2020

Eligibility

Participant type(s)Patient
Age groupAdult
SexBoth
Target number of participants30
Key inclusion criteria1. Mammary carcinoma
2. Planned trastuzumab therapy
Key exclusion criteria1. Any absolute contraindication for MRI
2. Chronic renal failure with GFR <30 ml/min/m2 at time of inclusion
Date of first enrolment30/11/2018
Date of final enrolment31/07/2020

Locations

Countries of recruitment

  • Germany

Study participating centre

HELIOS Hospital Berlin-Buch
Schwanebecker Chaussee 50
Berlin
13125
Germany

Sponsor information

Working Group Cardiac MRI @ Charité University Medicine Berlin & HELIOS Hospital Berlin-Buch
University/education

Lindenberger Weg 80
Berlin
13125
Germany

ROR logo "ROR" https://ror.org/05hgh1g19

Funders

Funder type

University/education

Working Group Cardiac MRI @ Charité University Medicine Berlin & HELIOS Hospital Berlin-Buch

No information available

Results and Publications

Intention to publish date31/12/2020
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot expected to be made available
Publication and dissemination planWe are intending to publish at least one research article in a high-ranking peer-reviewed journal, such as JCMR (impact factor 6.5)
IPD sharing planThe datasets generated during and/or analysed during the current study are not expected to be made available due to reasons of data protection laws in Germany. However, upon request methodology and data set structure can be shared.

Editorial Notes

23/11/2018: Internal review.