Evaluation of Cardiac and Endothelial Function in Children and Adolescents Treated With Anthracycline

NCT07253077 | Not Yet Recruiting

• 1 other identifier: 7304
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

In recent decades, the survival rate of children with cancer has increased significantly thanks to personalized treatments and the adoption of international therapeutic protocols. However, along with this increase in survival, side effects related to these treatments on various organs and systems have been observed. Among the most widely used chemotherapeutic agents in pediatric age, anthracyclines play a crucial role in the treatment of various forms of neoplasms (both haematological such as acute lymphoblastic leukemia or lymphomas, and solid tumors such as sarcomas). However, in addition to their excellent antineoplastic effect, they are burdened by the potential for cardiotoxicity. This cardiotoxicity manifests clinically with left ventricular systolic dysfunction and arrhythmias. At the moment, international guidelines recommend long-term cardiac follow-up evaluations for this group of patients, even after treatment has concluded.The methods used in the cardiac follow-up of patients undergoing anthracycline therapy include echocardiography, cardiac magnetic resonance imaging, tests to assess endothelial function, and measurements of the biomarkers troponin and atrial natriuretic peptide. These methods can assess anthracycline-induced cardiac and endothelial damage once it has already occurred, but they cannot predict its onset nor can they study its pathogenesis. Furthermore, to date, no information is available regarding the possibility of using "endothelial-mesenchymal transition" biomarkers as predictors of the onset of anthracycline-induced cardiac damage. This study analyzes these biomarkers as predictive tools for cardiac damage. Specifically, plasma levels of Serpin 3, THBS1, TGFbeta1, HIF1a, extracellular ICAM1, troponin, proBNP, fibrinogen, von Willebrand factor, and endothelin will be measured in patients treated with anthracycline. The concentrations of these biomarkers will be compared with the results of the echocardiogram and with the treatments performed in order to identify any relationships. Furthermore, plasma levels of Serpin 3, THBS1, TGFbeta1, HIF1a, extracellular ICAM1, troponin, proBNP, fibrinogen, von Willebrand factor, and endothelin will also be measured in a population of healthy subjects in order to obtain data on a possible relationship between the biomarkers and the anthracycline therapies performed.

Conditions

Anthracycline Related Cardiotoxicity in Childhood Cancers; Chemotherapeutic Toxicity; Childhood Cancer Survivors

Keywords

Childhood cancer survivors; Anthracycline related cardiotoxicity; Chemotherapy long term side effects; Cancer survivor follow up

Outcome Measures

Primary Outcomes (2)

• To assess the possible presence of differences in the concentration of early biomarkers of "endothelial-mesenchymal transition" and endothelial damage between subjects treated with anthracycline therapy and healthy controls.

  Measurement of the concentration of biomarkers of endothelial-mesenchymal transition and endothelial damage (Serpin 3, THBS1, TGF-beta1, HIF1a, extracellular ICAM1, troponin, proBNP, fibrinogen, von Willebrand factor, endothelin) in patients who had recovered from cancer and underwent anthracycline therapy and compared with controls.

  Biomarker assays will be performed only upon enrollment.

• To evaluate possible associations between measured biomarkers and echocardiogram results and medical history in subjects treated with anthracycline therapy.

  Measurement of the linear correlation between biomarkers and the results obtained in the echocardiographic examination and the treatments performed.

  Biomarkers and medical history will be collected at the moment of enrollement in the study

Study Arms (2)

Patients treated with anthracyclines

Patients who recovered from cancers and who underwent treatment with anthracyclines (from January 2010 to November 2024) and are undergoing regular follow-up. Inclusion criteria for the patient group: * diagnosis of hematologic oncology during childhood (diagnosis made between 0 and 16 years of age); * age at enrollment greater than or equal to 6 years; * having received anthracycline chemotherapy; * disease remission for at least 1 year; * absence of known cardiac disease prior to anthracycline therapy; * absence of congenital heart disease.

Diagnostic Test: Biomarker detection

Control group

Subjects never treated with anthracyclines and free of cancer. Inclusion criteria for the control group: * Age at enrollment greater than or equal to 6 years; * Good health.

Diagnostic Test: Biomarker detection

Interventions

Biomarker detection DIAGNOSTIC_TEST

All patients will be tested for plasma levels of Serpin 3, THBS1, TGFbeta1, HIF1a, extracellular ICAM1, and endothelin. In addition, the study will collect the following anamnestic data: * patient demographics, clinical data (age, sex, presence of comorbidities, medical history), instrumental data (echocardiogram performed), and laboratory data; * data relating to the neoplastic pathology and treatment performed

Patients treated with anthracyclines

Eligibility Criteria

• Age: 6 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The patient group will be selected among patients who have undergone anthracycline therapy and are undergoing regular follow-up at the Pediatric Oncology Unit of the Fondazione Policlinico Universitario A. Gemelli in Rome. Information about the tumor, treatments, and cardiac monitoring (echocardiogram) must be available for all patients. The control group will be selected from patients who visit the Pediatric Oncology Unit for a hematological evaluation but who have never undergone anthracycline therapy and have no known cardiac problems. All subjects (patients and controls) will undergo a thorough medical history and a clinical assessment, including a physical examination and measurement of vital signs and anthropometric parameters. Furthermore, all enrolled subjects, both patients and controls, will be required to collect, at a routine blood sampling time, a 6 ml tube for the measurement of biomarkers of endothelial-mesenchymal transition and endothelial activation.

You may qualify if:

• diagnosis of cancer during childhood (diagnosis made between 0 and 16 years of age);
• age at enrollment greater than or equal to 6 years;
• having received anthracycline chemotherapy;
• disease remission for at least 1 year;
• absence of known cardiac disease prior to anthracycline therapy;
• absence of congenital heart disease.

You may not qualify if:

• disease remission for less than 1 year;
• age less than 6 years at the time of enrollment;
• presence of known comorbidities (cardiopulmonary diseases, neurological diseases, etc.).
• age at the time of enrollment: 6 years or older;
• good health.
• having had oncological diseases;
• having undergone thoracic radiotherapy;
• having undergone anthracycline chemotherapy;
• being under 6 years of age at the time of enrollment;
• having known comorbidities (cardiopulmonary diseases, neurological diseases, etc.).

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168, Italy

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Peripheral blood samples for the measurement of biomarkers Serpin 3, THBS1, TGFbeta1, HIF1a, extracellular ICAM1, and endothelin

Study Officials

• Antonio Ruggiero

  Fondazione Policlinico Universitario A. Gemelli, IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Antonio Ruggiero, MD

CONTACT

+39 0630158305; antonio.ruggiero@unicatt.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2025
• First Posted: November 28, 2025
• Study Start: November 1, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: November 28, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)