Clinical trial NCT04586894: Adverse Myocardial and Vascular Side Effects of Immune Checkpoint Inhibitors
Official title: Atteintes Myocardiques, péricardiques et Vasculaires Sous Simple et/ou Double immunothérapie Anti-cancéreuse Anti-PD1, antiPDL1 et Anti-CTLA4
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cancer
Immune Defect
Cardiovascular Abnormalities
Keywords: Cardiotoxicity
Immune checkpoint inhibitors
Cancer
Myocarditis
Pericarditis
Myositis
Thrombotic events
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Fédération Française de Cardiologie
name: BioSerenity
First posted: 2020-10-14
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients undergoing ICI therapy for cancer before the start of treatment.

Brief 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.

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Number of patients with major cardiovascular advserse drug reactions
timeFrame: 6 weeks
Secondary outcomes:
measure: Number of patients with major cardiovascular advserse drug reactions
timeFrame: 6 months
measure: Number of patients with other cardiovascular advserse drug reactions
timeFrame: 6 weeks and 6 months
measure: Number of patients with isolated CMR abnormalities
timeFrame: 6 weeks and 6 months
measure: Number of patients with rhythm abnormalities that do not fullfill major advsere event criteria
timeFrame: 6 weeks and 6 months
measure: Risk factors for cardiovascular adverse drug event
timeFrame: 6 weeks and 6 months
Other outcomes:
measure: Biomarkers level of heart failure
timeFrame: Baseline
measure: Cytokinic biomarkers level
timeFrame: Baseline
Locations:
city: Paris
country: France
facility: AP-HP - Hôpital européen Georges-Pompidou
Study officials:
affiliation: Inserm U970 Paris Cardiovascular Research Center
name: Mariana Mirabel, MD
role: PRINCIPAL_INVESTIGATOR
References: