Plain English Summary
Background and study aims
It has been known since the 1970s that chemotherapy with anthracyclines can have adverse side effects on heart function. Between 5 and 30% of all patients treated with anthracyclines develop a decrease in heart function. Nevertheless, anthracyclines play a pivotal role in the treatment of many cancers, such as breast cancers and cancer of the connective tissue (sarcomas). With the fortunate development of increasing numbers of cancer survivors the long-term side effects of chemotherapy become more and more important. The current strategy of assessment of patients for development of heart failure under chemotherapy is mainly based on close observation using ultrasound. There is currently no reliable tool for predicting heart failure under chemotherapy before it actually occurs, or tools for identifying patients at highest risk. MRI is the gold standard for assessment of heart function and has the unique ability to also assess changes in the heart muscle which are known to predict the development of subsequent heart failure. It is thought that chemotherapy with anthracyclines leads to very early changes in the tissue of the heart muscle. These changes may be detectable by MRI and may help to predict the development of heart failure at a much later point in time. Hence, the aim of this study is to assess changes in the heart tissue before and very early (24-48 hours) after the first treatment with anthracyclines using MRI and compare these changes to the development of heart function at the end of chemotherapy treatment (usually after 4-5 months) also assessed by MRI.
Who can participate?
Patients aged at least 18 with sarcoma undergoing chemotherapy with anthracyclines
What does the study involve?
All patients receive three standard MRI scans - one scan before the start of chemotherapy, one 24-48 hours after the first treatment and one 3-4 weeks after the end of chemotherapy. The first and the last MRI scan are part of a normal exam and only the second MRI scan is performed merely due to study participation. Participants also provide blood samples and their heart electrical activity is recorded (electrocardiography [ECG]) at the time of each MRI scan.
What are the benefits and risk of participating?
Benefits include a closer observation of heart function through participation in this study. Extraordinary findings are reported to the referring doctors. One of the three MRI scans is additional and merely performed due to study participation. Since the other two MRI scans are performed anyway, there is no additional burden from a patient's perspective besides the single additional MRI exam.
Where is the study run from?
HELIOS Clinic Berlin-Buch (Germany)
When is the study starting and how long is it expected to run for?
October 2014 to December 2016
Who is funding the study?
1. Charité Universitätsmedizin Berlin (Germany)
2. HELIOS Kliniken (Germany)
Who is the main contact?
Prof. Jeanette Schulz-Menger
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
CARETOX-1
Study information
Scientific title
Assessment of the predictive value of cardiac MRI in anthracycline-induced cardiomyopathy in sarcoma patients
Acronym
CARETOX-1
Study hypothesis
Early changes in cardiac tissue morphology assessable by cardiac MRI can predict the development of subsequent cardiomyopathy in sarcoma patients treated with anthracyclines.
Ethics approval
Ethics board at Charité University Medicine Berlin, Campus Mitte, 23/09/2014, ref: EA1/262/14
Study design
Observational cohort study
Primary study design
Observational
Secondary study design
Cohort study
Trial setting
Hospitals
Trial type
Diagnostic
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet.
Condition
Sarcoma
Intervention
Cardiac tissue morphology is assessed in sarcoma patients treated with anthracycline-based chemotherapy using cardiac MRI. Patients receive at least three cardiac MRI scans: before start of chemotherapy (baseline), 24-48 hours after the first treatment and 3-4 weeks after completion of chemotherapy (usually after 4-5 months).
Blood analysis is carried out at the time of each MRI scan: NTproBnP, high-sensitive Troponin T, hematocrit, glomerular filtration rate. ECG is also carried out at the time of each MRI scan.
Intervention type
Phase
Drug names
Primary outcome measure
Myocardial T1 and T2 times, measured using parametric mapping techniques before start of chemotherapy (baseline), 24-48 hours after the first treatment and 3-4 weeks after completion of chemotherapy (usually after 4-5 months).
Secondary outcome measures
Measured before start of chemotherapy (baseline), 24-48 hours after the first treatment and 3-4 weeks after completion of chemotherapy (usually after 4-5 months):
1. Left and right atrial and ventricular size and function, measured in CINE sequences
2. Detection and size of myocardial fibrosis using late gadolinium enhancement techniques
3. Detection of arrhythmia using ECG
4. Laboratory blood analysis parameters (NTproBNP, hematocrit, high sensitive troponin T, glomerular filtration rate)
Overall trial start date
01/10/2014
Overall trial end date
31/12/2016
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Histologically confirmed sarcoma diagnosis
2. Planned chemotherapy with anthracyclines (cumulative dose >300 mg/m2 doxorubicin-equivalent)
3. Age at least 18 years (no upper limit)
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
30 patients with first exposition to anthracyclines, 30 patients with re-exposition with anthracyclines
Participant exclusion criteria
1. Any contraindication for contrast-based MRI
2. Chronic renal failure (glomerular filtration rate <30ml/min)
3. Previous participation in this study
Recruitment start date
01/10/2014
Recruitment end date
31/12/2019
Locations
Countries of recruitment
Germany
Trial participating centre
HELIOS Clinic Berlin-Buch
13125
Sponsor information
Organisation
Charité University Medicine Berlin
Sponsor details
Working Group Kardiale MRT
Lindenberger Weg 80
Berlin
13125
Germany
Sponsor type
University/education
Website
Funders
Funder type
University/education
Funder name
Charité Universitätsmedizin Berlin
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
Germany
Funder name
HELIOS Kliniken
Alternative name(s)
HELIOS Kliniken GmbH
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
Germany
Results and Publications
Publication and dissemination plan
Results of this study shall be published in two high-ranking peer-reviewed journal publication. One publication for each study group (group 1: first exposure to anthracyclines, group 2: re-exposure to anthracyclines - for details see above).
IPD sharing statement
The datasets generated during and/or analysed during the current study are not expected to be made available due to data protection laws in Germany. However, upon request methodology and dataset structure can be shared.
Intention to publish date
28/02/2018
Participant level data
Not expected to be available
Basic results (scientific)
Publication list