Vascular Toxicities of Immune ChecKpoint Inhibitors : From Bed to Benchside (VICKI)
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed 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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
-
Paris, France
- Institut Mutualiste Montsouris
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: ICIs alone
Participants on ICIs alone
|
Arterial Doppler (ultrasound, no radiation, no contrast agent) and blood sampling twice for participants on ICIs
Other Names:
|
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Experimental: ICIs + VEGF inhibitors
Participants on ICIs + VEGF inhibitors
|
Arterial Doppler (ultrasound, no radiation, no contrast agent) and blood sampling twice for participants on ICIs
Other Names:
|
|
Experimental: ICIs + chemotherapy
Participants on ICIs + chemotherapy
|
Arterial Doppler (ultrasound, no radiation, no contrast agent) and blood sampling twice for participants on ICIs
Other Names:
|
|
Sham Comparator: Controls
Participants on other than ICIs cancer therapies
|
Arterial Doppler (ultrasound, no radiation, no contrast agent) and blood sampling twice for participants on ICIs
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Endothelial dysfunction
Time Frame: 6 weeks
|
Surrogate marker of endothelial dysfunction : Signifiant FMD variation on ICIs as defined by the International Cardio-Oncology Society
|
6 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Correlation of blood biomarkers to endothelial dysfunction (surrogate marker: Flow Mediated Dilatation variation)
Time Frame: 6 weeks
|
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
|
|
Major cardiovascular event (MACE)
Time Frame: 6 months
|
Collection of clinically relevant MACE at clinical follow-up: acute coronary syndrome; coronary angioplasty; stroke; cardiac suddent death, myocarditis, myositis.
|
6 months
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Urogenital Diseases
- Cardiovascular Diseases
- Urogenital Neoplasms
- Neoplasms by Site
- Male Urogenital Diseases
- Kidney Diseases
- Urologic Diseases
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Neoplasms by Histologic Type
- Neoplasms, Glandular and Epithelial
- Adenocarcinoma
- Urologic Neoplasms
- Carcinoma
- Kidney Neoplasms
- Urinary Bladder Diseases
- Arteriosclerosis
- Arterial Occlusive Diseases
- Neoplasms
- Carcinoma, Renal Cell
- Vascular Diseases
- Urinary Bladder Neoplasms
- Atherosclerosis
- Investigative Techniques
- Specimen Handling
- Clinical Laboratory Techniques
- Diagnostic Techniques and Procedures
- Diagnosis
- Punctures
- Surgical Procedures, Operative
- Blood Specimen Collection
Other Study ID Numbers
- CARDIO 05 2022
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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