Serial Cardiac Magnetic Resonance Imaging (CMR) With Contrast Agents and Biomarker Analysis for the Detection of Cardiotoxicity Under Anthracycline-containing Cancer Therapy

Condition(s) studied

Investigational drug(s) / intervention(s)

CMR based measurement of cardiotoxicity: CMR is performed on a 1.5T Siemens Magnetom Aera. The examination follows clinically established protocols for assessing cardiac morphology and function using HASTE and CINE-SSFP sequences. CINE and late gadolinium enhancement (LGE) images of the short axis are taken every 10 mm from the base of the heart to the apex (6 mm slice, resolution 1.2 × 1.8 mm). LGE images are acquired 5-10 minutes after administration of gadolinium. T1 mapping is performed using a MOLLI sequence before and 20 minutes after contrast agent administration, T2 mapping using an ECG-triggered T2-prepared SSFP sequence before contrast agent administration. The evaluation is performed independently by two examiners with manual marking of endocardial and epicardial boundaries. Left ventricular volumes and ejection fraction are calculated using the summation method, and LGE is visually quantified and classified. In addition, T1, ECV, and T2 maps are created from motion-corrected images and global values are calculated

biosampling for scientific research in study-specific biobank: As part of the study, additional biomaterial (blood, urine, stool) will be collected at defined time points. A study-specific biobank will be created. Blood samples will be taken at baseline, mid-point analysis, and 3 and 12 months after the end of therapy. The methods used will analyze the DNA, RNA, and protein levels of the stored tissue material and perform functional tests. Genetic variants will be detected using established methods such as real-time PCR methods, mass spectrometric detection or nanofluid technology, as well as DNA microarrays or genome sequencing. Endogenous metabolites or metabolite profiles as well as drug concentrations and their metabolites can be detected in blood, urine, and, if necessary, stool using various mass spectrometric methods as well as biochemical assays. The cytokine profile can be analyzed in plasma isolated from blood samples. Proinflammatory cytokines in doxorubicin-induced cardiotoxicity have been described and should therefore be determined.

Study summary

The goal of the trial is the early detection of cardiotoxicity in patients treated with anthracycline-based chemotherapy. Current diagnostics, such as troponin T, NT-pro-BNP, electrocardiogram, and echocardiography, are not able to identify early myocardial damage. Therefore, this study aims to identify early myocardial damage by using cardiac magnetic resonance imaging.

The primary endpoint of this study is the change in relaxation times in CMR before, during, and after therapy.

Furthermore, the study analyzes:

* other abnormal results in CMR
* changes in troponin T and NT-pro-BNP
* changes in global longitudinal strain in echocardiography and correlation with results of CMR
* detection of new biomarkers in blood, urine, or stool

Eligibility

Primary outcome measure(s)

• Change of T2-weighted myocardial relaxation time in cardiac magnetic resonance imaging — Baseline (before anthracycline administration), after 4-9 weeks (depending on the anthracycline-based treatment regimen used), 3 months after completion of therapy, and 12 months after completion of therapy.
  T2 mapping using an ECG-triggered T2-prepared SSFP sequence before contrast agent administration. The evaluation is performed independently by two examiners with manual marking of endocardial and epicardial boundaries.

Trial sites (1)

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