Adverse Myocardial and Vascular Side Effects of Immune Checkpoint Inhibitors

Cancer Clinical Trial

— AMICI  

Official title:

Atteintes Myocardiques, péricardiques et Vasculaires Sous Simple et/ou Double immunothérapie Anti-cancéreuse Anti-PD1, antiPDL1 et Anti-CTLA4

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04586894
• Other study ID #: APHP191048
• Secondary ID: 2020-A01502-37
• Status: Completed
• Start date: November 6, 2020
• Est. completion date: July 1, 2022

Study information

• Verified date: June 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Our knowledge on cardiovascular side effects of immune checkpoint inhibitors (ICIs) is restricted to this date to observational retrospective data (mainly case series and pharamcovigilance analysis). We aim at assessing the incidence of cardiovascular adverse side effects of ICIs by means of a prospective interventional single centre study using multiple biomarkers.

Description:

Immune checkpoint inhibitors (ICIs) are drastically improving cancer prognosis. Cardiovascular adverse side effects of ICIs are though to be rare but may be responsible for ~50% death rates.

Prospective screening for cardiovascular and muscular immune related side effects has not been undertaken independently from the industry.

The aim is to describe the incidence of these side effects by means of serial assessment in patients undergoing ICI therapy for cancer. Biomarkers as ECG, echocardiography, cardiac magnetic resonance imaging and long-term ECG monitoring will be undertaken at inclusion (before ICI therapy is started), and during the first cycle treatments and at 6 months follow-up.

Mean endpoint encompasses cardiovascular and muscular adverse side effects between the 2nd and the 3rd ICI cycle. Secondary endpoints include cardiovascular and muscular adverse side effects at 6 months follow-up, and the incidence of individual side effects.

4 ancillary studies based on patients' blood biobanking are also planned. Their objectives are:

• to assess sensitivity of heart failure biomarkers in predicting cardiovascular events under ICI,

• to assess sensitivity of cytokine biomarkers in predicting cardiovascular events under ICI,

• to bank cells to induce cardiomyocytes from stem cells

• to bank DNA to identify genetic factors related to occurrence of cardiovascular events under ICI

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: July 1, 2022
• Est. primary completion date: February 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• prescribed treatment by immune checkpoint inhibitors (ICI) for cancer

Exclusion Criteria:

• previous treatment by any ICI

• any contraindication to cardiac resonance magnetic imaging

• contraindication to gadoteric acid, meglumin or any gadolinium-based contrast agent

• pace maker or automated implantable defibrilator

• pregnancy, breastfeeding

• women of childbearing potential who do not use one of the following methods of birth control: hormonal contraception or intrauterine device or bilateral tubal occlusion

• patient under legal protection

• renal failure defined by creatinine clearance <30ml/min/m² (CKD-EPI)

• current participation or exclusion period of another interventional clinical study

Exclusion Criteria for ancillary studies:

• hemoglobinemia < 9 g/dl

Related Conditions & MeSH terms

• Cancer
• Cardiovascular Abnormalities
• Immune Defect

Intervention

Diagnostic Test:
• Cardiac MRI
Gadolinium-enhanced magnetic resonance imaging of the heart before the first cycle of chemotherapy

Device:
• Smart cloth
A smart cloth recording cardiac and hemodynamic parameters will be worn by patients during 42 days. Replaced by a holter monitor if the smart cloth is refused or not tolerated by the patient.

Other:
• Biobanking
Blood samples (plasma, serum, DNA, stem cells, immune cells) taken as part of the study will be stored in a biological sample collection. These samples may be used for further analysis not described in the initial protocol but which may be useful for investigation or in light of advances in scientific knowledge.

Locations

Country	Name	City	State
France	AP-HP - Hôpital européen Georges-Pompidou	Paris

Sponsors (3)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	BioSerenity, Fédération Française de Cardiologie

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Biomarkers level of heart failure		Baseline
Other	Cytokinic biomarkers level		Baseline
Primary	Number of patients with major cardiovascular advserse drug reactions	Incidence of a composite endpoint including myocarditis, pericarditis, acute coronary syndrome, acute heart failure, subclinial cardio-toxicity, high degree conduction abormalities or ventricular sustained arrythmias, cardiovascular death.	6 weeks
Secondary	Number of patients with major cardiovascular advserse drug reactions	Incidence of a composite endpoint including myocarditis, pericarditis, acute coronary syndrome, acute heart failure, subclinial cardio-toxicity, high degree conduction abormalities or ventricular sustained arrythmias, cardiovascular death.	6 months
Secondary	Number of patients with other cardiovascular advserse drug reactions	Incidence of a composite endpoint including vasculitis or myositis.	6 weeks and 6 months
Secondary	Number of patients with isolated CMR abnormalities	Serial assessment	6 weeks and 6 months
Secondary	Number of patients with rhythm abnormalities that do not fullfill major advsere event criteria	Burden of extrasystole, low degree conduction disorders	6 weeks and 6 months
Secondary	Risk factors for cardiovascular adverse drug event	Characterization of risk predictors for occurrence of cardiovascular adverse drug event, among the following: socio-demographic characteristics, oncologic characteristics, previous treatments, serum biomarkers, patient assessment on ESC-SCORE and ACC/AHA ASCVD risk scoring systems, immune status, cardiac characteristics on imaging.	6 weeks and 6 months