Extensive CArdioVAscular Characterization and Follow-up of Patients Receiving Immune Checkpoint Inhibitors

NCT05699915 | Terminated

• 1 other identifier: MMS.2021.058
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 4

Brief Summary

The goal of this prospective, multicentre study is to investigate short- and long-term cardiovascular effects in cancer patients treated with immune checkpoint inhibitors (ICIs). The main question\[s\] it aims to answer are:

• To investigate troponin and NT-proBNP values in patients receiving ICIs and their association with ICI-induced CV abnormalities and MACEs.
• Study the calcium score, systolic, and diastolic (dys)function.
• Evaluate associations between patient/disease characteristics / transthoracic echocardiography parameters / electrocardiography parameters and troponin / NT-proBNP levels. Participants will be closely monitored by performing the following additional visits and testing:
• Chest CT scan prior to treatment start, after 12 and 24 months.
• Consultation with a cardiologist at baseline, 3, 6, 12 and 24 months, who will perform an electrocardiogram and echocardiogram.
• One additional blood sample prior to treatment start, after 3, 6, 12 and 24 months. An extra blood sample could be taken in case of sudden heart problems.
• Non-invasive endothelial function tests prior to treatment start, after 12 and 24 months.

Conditions

Cancer; Immune-related Adverse Event; Cardiac Abnormalities, Variable; Immune Checkpoint Inhibitor-Related Myocarditis; Diastolic Dysfunction; Atherosclerosis; Cardiotoxicity

Keywords

Cardio-oncology; Immune-related adverse event; Immune checkpoint inhibitor; Myocarditis; Troponin

Outcome Measures

Primary Outcomes (1)

• The incidence of an elevated hs-TnT above the ULN if the baseline value was normal; or 1.5 ≥ times baseline if the baseline value was above the ULN within the first three months of treatment. The maximum measured value will be taken into account.

  For the primary endpoint, the cumulative incidence of troponin elevation will be calculated with death as a competing risk. Cumulative incidences and corresponding 95% confidence intervals will be reported and a cumulative incidence plot will be used to visualize the results.

  Preliminary analysis once 50 patients have reached their 3-month cardiac follow-up visit and 3 months after last patient is included.

Secondary Outcomes (25)

• The incidence of hs-TnT/NT-proBNP elevations at 6, 12, and 24 months.

  Through study completion, an average of 1 year

• The incidence of hs-TnT/NT-proBNP elevations at baseline, 3, 6, 12, and 24 months.

  Preliminary analysis once 50 patients have reached their 3-month cardiac follow-up visit and through study completion, an average of 1 year

• Evolution of hs-TnT/NT-proBNP in 24 months compared to baseline.

  Through study completion, an average of 1 year

• Evolution of transthoracic 3D echocardiography parameters (dimensions, diastolic function, valvular abnormalities, LVEF, strain analysis) at baseline, 3, 6, 12, and 24 months.

  reliminary analysis once 50 patients have reached their 3-month cardiac follow-up visit and through study completion, an average of 1 year

• Evolution of electrocardiography parameters (rhythm, heart axis, PQ interval, QRS duration, bundle branch block, QT interval, RR interval, pathological Q's, left ventricular hypertrophy and STT segments) at baseline, 3, 6, 12, and 24 months.

  reliminary analysis once 50 patients have reached their 3-month cardiac follow-up visit and through study completion, an average of 1 year

Study Arms (1)

Cancer patients with a solid tumour eligible for treatment with immune checkpoint inhibitors

OTHER

Patients are treated as standard of care

Procedure: Cardiology consultation; Diagnostic Test: Chest Computed Tomography (CT) without contrast; Procedure: Non-invasive endothelial function tests; Procedure: Electrocardiogram; Diagnostic Test: Extra serum sample (7.5 mL)

Interventions

Cardiology consultation PROCEDURE

* Electrocardiogram (ECG). * Echocardiogram: A comprehensive evaluation of systolic and diastolic function, ventricular and atrial geometry will be performed. Special attention will be given to acquire a 3D measurement of left ventricular ejection fraction (LVEF) and to perform deformation imaging of left ventricle (global longitudinal strain (GLS)). The right ventricular function will be evaluated by tricuspid annular plane systolic excursion (TAPSE) and peak systolic velocity S' derived from color coded tissue Doppler imaging (TDI). Diastolic dysfunction will be based on average E/e' ratio \> 15 and left atrial (LA) area \> 30 cm2.

Cancer patients with a solid tumour eligible for treatment with immune checkpoint inhibitors

Chest Computed Tomography (CT) without contrast DIAGNOSTIC_TEST

Calcium score. This will be performed at baseline, 12 and 24 months. The scans at 12 and 24 months will be combined, if possible, with standard of care scans for cancer treatment.

Also known as: Cardiac CT

Cancer patients with a solid tumour eligible for treatment with immune checkpoint inhibitors

Non-invasive endothelial function tests PROCEDURE

* FMD * PAT This aspect of the study will only be performed in the patients included by the Antwerp University Hospital due to organizational/practical issues.

Also known as: Flow mediated dilatation (FMD), Peripheral arterial tonometry (PAT)

Cancer patients with a solid tumour eligible for treatment with immune checkpoint inhibitors

Electrocardiogram PROCEDURE

An ECG will be taken prior to each ICI cycle during the first three months of treatment.

Also known as: ECG

Cancer patients with a solid tumour eligible for treatment with immune checkpoint inhibitors

Extra serum sample (7.5 mL) DIAGNOSTIC_TEST

An extra serum sample will be taken at baseline, 3, 6, 12, 24 months and in case of sudden cardiac problems. This will subsequently be analysed to determine high-sensitivity troponin I, high-sensitivity troponin T and NT-proBNP.

Cancer patients with a solid tumour eligible for treatment with immune checkpoint inhibitors

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a solid tumour and will receive one of the following therapies based on current evidence based clinical guidelines: anti-programmed cell death protein-1 (PD-1), anti-programmed cell death ligand-1 (PD-L1) and/or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) therapy
• Be literate in Dutch or English

You may not qualify if:

• Prior treatment with immunotherapy (immune checkpoint inhibitors, T-cell transfer therapy, cancer treatment vaccines or immune system modulators).
• Patients who will receive ICIs in combination with an additional systemic anti-cancer regimen (chemotherapy, tyrosine kinase inhibitors,…).
• Having a known history of human immunodeficiency virus (HIV) infection.
• Having a known history of hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known active hepatitis C virus (defined as detectable RNA via qualitative nucleic acid testing) infection.
• Having a diagnosis of immunodeficiency or is receiving chronic/active systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent)

Sponsors & Collaborators

• Algemeen Ziekenhuis Maria Middelares: lead

Study Sites (4)

Antwerp University Hospital

Antwerp, Antwerp, 2650, Belgium

Location

AZ Sint-Vincentius Deinze

Deinze, East-Flanders, 9800, Belgium

Location

Algemeen Ziekenhuis Maria Middelares

Ghent, East-Flanders, 9000, Belgium

Location

AZ Sint-Elisabeth Zottegem

Zottegem, East-Flanders, 9620, Belgium

Location

Related Publications (1)

• Delombaerde D, De Sutter J, Croes L, Vervloet D, Moerman V, Van de Veire N, Willems AM, Wouters K, Peeters M, Prenen H, Vulsteke C. Extensive CArdioVAscular Characterization and Follow-Up of Patients Receiving Immune Checkpoint Inhibitors: A Prospective Multicenter Study. Pharmaceuticals (Basel). 2023 Apr 20;16(4):625. doi: 10.3390/ph16040625.

  PMID: 37111382 DERIVED

MeSH Terms

Conditions

Neoplasms; Atherosclerosis; Cardiotoxicity; Myocarditis

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries; Cardiomyopathies

Study Officials

• Christof Vulsteke, Prof

  Algemeen Ziekenhuis Maria Middelares

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Integrated Cancer Center Ghent

Study Record Dates

• First Submitted: December 9, 2022
• First Posted: January 26, 2023
• Study Start: January 7, 2022
• Primary Completion: July 12, 2024
• Study Completion: July 12, 2024
• Last Updated: January 30, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

BE (4)