Vascular Toxicities of Immune ChecKpoint Inhibitors : From Bed to Benchside

Cancer Clinical Trial

— VICKI  

Official title:

Vascular Toxicities of Immune ChecKpoint Inhibitors : From Bed to Benchside

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06020651
• Other study ID #: CARDIO 05 2022
• Status: Recruiting
• Phase: N/A
• Start date: June 7, 2023
• Est. completion date: June 1, 2025

Study information

• Verified date: July 2023
• Source: Institut Mutualiste Montsouris
• Contact: Isabelle Sauret, MBS
• Phone: +33 1 56 61
• Email: isabelle.sauret[@]imm.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Immune checkpoint inhibitors (ICIs) are largely prescribed in a growing number of cancer diseases and at earlier stages (non metastatic cancer). Among immune-related adverse events, (iRAEs), the incidence of major cardiovascular events due to atherosclerosis reaches 13% at one year in patients at high risk. To the best of our knowledge, the mechanisms of this acceleration of atherosclerosis have not been studied to this date. The VICKI study aims at furthering our knowledge on the mechanisms of atherosclerotic plaque instability by means of a prospective single-centre pilot study, by comparing: - surrogate markers of clinical vasculo-toxicity with arterial Doppler (flow mediated reserve) as defined by the International Cardio-Oncology Society; - circulating biomarkers Before and after receiving ICIs for solid cancer treatment.

Description:

Context. Immune checkpoint inhibitors (ICIs) are largely prescribed in a growing number of cancer diseases and at earlier stages (non metastatic cancer). Among immune-related adverse events, (iRAEs), the incidence of major cardiovascular events due to atherosclerosis reaches 13% at one year in patients at high risk. To the best of our knowledge, the mechanisms of this acceleration of atherosclerosis have not been studied to this date. Endothelial dysfunction is a predictor of the development of atherosclerotic plaque and events related to erosion or rupture. Endothelial dysfunction correlates well with the increase of circulating microparticles in various populations. The increase of circulating microparticles is also associated with major cardiovascular events. The International society of Cardio-Oncology (IC-OS) recently published a definition for subclinical vascular toxicities due to ICIs. It includes non-invasive imaging methods readily available at the bedside (Herrmann et al. European Heart Journal 2022), largely replicated in the recent European Society of Cardiology (ESC) guidelines 2022. It includes the decrease of flow mediated reserve <7% or hyperhemia index <2; or the decrease of any of these biomarkers > 50% from baseline. Aims and Methods. The VICKI study aims at furthering our knowledge on the mechanisms of atherosclerotic plaque instability by means of a prospective single-centre pilot study, by comparing: - surrogate markers of clinical vasculo-toxicity with arterial Doppler (flow mediated reserve, hyperhemia index, plaque volume) as defined by IC-OS; - circulating microparticles; Before and after receiving ICIs for solid cancer treatment. The number of participants: - 40 patients receiving ICIs for solid cancer (alone or in combination of other cancer drugs); - 40 controls (matched by age, gender, cancer type) not treated by ICIs. Duration of participation: up to 6 weeks. Inclusion period: 12 months. Perspectives. The VICKI study may improve our understanding of the mechanisms of atherosclerosis mediated major cardiovascular events. If circulating biomarkers correlate well with Doppler surrogate markers of vascular toxicity, larger studies to refine prediction models could be undertaken. This would be a step forward personalized care for the prediction of major cardiovascular events on ICIs.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: June 1, 2025
• Est. primary completion date: December 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• All patients scheduled for first ICI therapy at our institution;
• Matched controls with cancer and no ICI therapy;

Exclusion Criteria:

• Major cardiovascular event in the past 6 months;
• Unable to provide informed consent;
• History of ICI therapy

Related Conditions & MeSH terms

• Bladder Cancer
• Cancer
• Carcinoma, Renal Cell
• Renal Cell Carcinoma

Intervention

Diagnostic Test:
• Arterial Doppler for Flow Mediated Reserve measurement
Arterial Doppler (ultrasound, no radiation, no contrast agent) and blood sampling twice for participants on ICIs

Locations

Country	Name	City	State
France	INstitut Mutualiste Montsouris	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Institut Mutualiste Montsouris	Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Endothelial dysfunction	Surrogate marker of endothelial dysfunction : Signifiant FMD variation on ICIs as defined by the International Cardio-Oncology Society	6 weeks
Secondary	Correlation of blood biomarkers to endothelial dysfunction (surrogate marker: Flow Mediated Dilatation variation)	Increase in microparticles (CD144+, CD31+/41-, CD62e+, CD235a+, CD41+, CD11+, CD3+); cytokines (e.g., IL-1b, IFNg, TNFa, VEGF-A, C, D, HGF); single-cell profiling and deep immunophenotyping.	6 weeks
Secondary	Major cardiovascular event (MACE)	Collection of clinically relevant MACE at clinical follow-up: acute coronary syndrome; coronary angioplasty; stroke; cardiac suddent death, myocarditis, myositis.	6 months