NCT07528586

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

Serial Cardiac Magnetic Resonance Imaging (CMR) With Contrast Agents and Biomarker Analysis for the Detection of Cardiotoxicity Under Anthracycline-containing Cancer Therapy - A Monocentric, Low Interventional Phase IV Pilot Study

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 93 (estimated)
• Sponsor: Robert Bosch Gesellschaft für Medizinische Forschung mbH (RBMF) · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Detailed description

The goal of the trial is the early detection of cardiotoxicity in patients treated with anthracycline-based chemotherapy as standard of care therapy. For clarification: Standard anthracycline-based chemotherapy is administered independently of the study and is not the subject of this study, but rather is its basis. No investigational medicinal products are being tested in this clinical trial; instead only diagnostic procedures are being investigated. Since current diagnostic methods-such as troponin T, NT-proBNP, electrocardiography, and echocardiography-are limited in their ability to detect early myocardial injury, the study aims to identify early myocardial damage using cardiac magnetic resonance imaging (CMR). Enrolled participants will be stratified into risk groups using the HFA-ICOS score and-depending on the risk category-monitored according to current ESC guidelines using electrocardiography, echocardiography, and serial measurements of troponin T and NT-proBNP. Preclinical data suggest that anthracyclines may impair myocardial function not only as a result of cumulative dosage over time but also during the early stages of therapy. The investigators therefore evaluate the use of CMR for the early detection of myocardial alterations during anthracycline therapy. CMR examinations will be scheduled according to the administered cumulative dose of anthracyclines. Following a baseline evaluation prior to the initiation of therapy, the first follow-up CMR examination will be performed after approximately half of the preplanned cumulative anthracycline dose has been administered. A third CMR examination will be conducted after completion of therapy. Twelve months after therapy completion, an end-of-study CMR examination will be performed to assess persistent myocardial changes. The primary endpoint is the measurement of myocardial relaxation times. Given the early time point of evaluation, additional CMR parameters will also be analyzed, including variations in cardiac morphology, cardiac function, late gadolinium enhancement, and myocardial perfusion. Currently, both the proportion of participants potentially affected by early myocardial alterations during anthracycline therapy and the underlying pathophysiological mechanisms remain unclear. The study therefore seeks to identify biomarkers or genetic polymorphisms associated with an increased risk of early myocardial injury. For this purpose, blood, urine, and stool samples will be collected for inclusion in a biobank and analyzed for polymorphisms or mutations in genes such as CYBA, RAC2, NCF4, ABCC1, ABCC5, ABCB4, SLC22A17, SLC22A7, SLC28A3, SLC10A2, HAS3, CBR3, RARG, CELF4, and SLC22A3. In addition, anthracycline metabolites and cytokine profiles, such as IL-6 and TNF-α, may be measured.

Conditions

• Cardiotoxicity
• Anthracycline-induced Cardiotoxicity

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	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
OTHER	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.

Timeline

• Start date: 2026-03-04
• Primary completion: 2029-08-01
• Completion: 2030-03-01
• First posted: 2026-04-14
• Last updated: 2026-04-14

Locations

1 site across 1 country: Germany