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Adverse Myocardial and Vascular Side Effects of Immune Checkpoint Inhibitors (AMICI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04586894
Recruitment Status : Not yet recruiting
First Posted : October 14, 2020
Last Update Posted : October 14, 2020
Sponsor:
Collaborators:
Fédération Française de Cardiologie
BioSerenity
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

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.

Condition or disease Intervention/treatment
Cancer Immune Defect Cardiovascular Abnormalities Diagnostic Test: Cardiac MRI Device: Smart cloth Other: Biobanking

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

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Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Atteintes Myocardiques, péricardiques et Vasculaires Sous Simple et/ou Double immunothérapie Anti-cancéreuse Anti-PD1, antiPDL1 et Anti-CTLA4
Estimated Study Start Date : October 2020
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Patients 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

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.




Primary Outcome Measures :
  1. Number of patients with major cardiovascular advserse drug reactions [ Time Frame: 6 weeks ]
    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.


Secondary Outcome Measures :
  1. Number of patients with major cardiovascular advserse drug reactions [ Time Frame: 6 months ]
    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.

  2. Number of patients with other cardiovascular advserse drug reactions [ Time Frame: 6 weeks and 6 months ]
    Incidence of a composite endpoint including vasculitis or myositis.

  3. Number of patients with isolated CMR abnormalities [ Time Frame: 6 weeks and 6 months ]
    Serial assessment

  4. Number of patients with rhythm abnormalities that do not fullfill major advsere event criteria [ Time Frame: 6 weeks and 6 months ]
    Burden of extrasystole, low degree conduction disorders

  5. Risk factors for cardiovascular adverse drug event [ Time Frame: 6 weeks and 6 months ]
    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.


Other Outcome Measures:
  1. Biomarkers level of heart failure [ Time Frame: Baseline ]
  2. Cytokinic biomarkers level [ Time Frame: Baseline ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients undergoing ICI therapy for cancer before the start of treatment.
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04586894


Contacts
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Contact: Aurélie Guimfack aurelie.guimfack@aphp.fr
Contact: Yvann Frigout yvann.frigout@aphp.fr

Locations
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France
AP-HP - hôpital européen Georges-Pompidou
Paris, France, 75015
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Fédération Française de Cardiologie
BioSerenity
Investigators
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Principal Investigator: Mariana Mirabel, MD Assistance Publique - Hôpitaux de Paris
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT04586894    
Other Study ID Numbers: APHP191048
2020-A01502-37 ( Other Identifier: Agence nationale de sécurité du médicament et des produits de santé )
First Posted: October 14, 2020    Key Record Dates
Last Update Posted: October 14, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared
Supporting Materials: Study Protocol
Informed Consent Form (ICF)
Time Frame: Two years after the last publication
Access Criteria:

Data sharing must be accepted by the sponsor and the PI based on a scientific project and scientific involvement of the PI team. Collaboration will be fostered.

Teams wishing obtain IPD must meet the sponsor and IP team to present scientific (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasibility and financial support will be discussed before mandatory contractual agreement. Processing of shared data must comply with European General Data Protection Regulation (GDPR).


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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Cardiotoxicity
Immune checkpoint inhibitors
Cancer
Myocarditis
Pericarditis
Myositis
Thrombotic events
Additional relevant MeSH terms:
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Cardiovascular Abnormalities
Congenital Abnormalities
Cardiovascular Diseases