CHIMeRA: Immune CHeckpoint Inhibitors Monitoring of Adverse Drug ReAction

Sponsor

Groupe Hospitalier Pitie-Salpetriere (Other)

Overall Status

Completed

CT.gov ID

NCT03492242

Collaborator

Institut National de la Santé Et de la Recherche Médicale, France (Other)

1,000

Enrollment

Location

7.9

Actual Duration (Months)

126.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Immune checkpoint inhibitors (ICIs) might have high grade immune-related adverse events (irAEs) from rhumatologic, endocrinologic, cardiac or other system origin. This study investigates reports of drug induced irAEs with treatment including anti-PD1, Anti-PDL-1, and Anti-CTLA4 classes using the World Health Organization (WHO) database VigiBase and the french database Base Nationale de PharmacoVigilance (BNPV).

Condition or Disease	Intervention/Treatment	Phase
Arthritis Cancer Cardiac Disease Endocrine System Diseases Autoimmune Diseases Ophthalmopathy Myositis Neuropathy	Drug: Immune checkpoint inhibitor

Detailed Description

Immune checkpoint inhibitors (ICIs) have dramatically improved clinical outcomes in multiple cancer types and are increasingly being tested in earlier disease settings and used in combination. However, immune-related adverse events (irAEs) can occur. Here the investigators use VigiBase (http://www.vigiaccess.org/), the World Health Organization (WHO) database of individual safety case reports, and in the Base Nationale de PharmacoVigilance (BNPV) which is the french pharmacovigilance database, to identify cases of adverse drug reaction including arthiritis, auto-immune induced diseases, cardiac diseases, endocrinologic diseases, following treatment with ICIs.

Study Design

Study Type:

Observational

Actual Enrollment :

1000 participants

Observational Model:

Case-Only

Time Perspective:

Cross-Sectional

Official Title:

Monitoring of Immune Checkpoint Inhibitors Adverse Drug Reactions Through the WHO Vigilyze and French Pharmaco-vigilance Database (Base Nationale de Pharmacovigilance BNPV)

Actual Study Start Date :

Feb 1, 2018

Actual Primary Completion Date :

Sep 30, 2018

Actual Study Completion Date :

Sep 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Adverse drug reaction induced by immune checkpoint inhibitors Case reported in the World Health Organization (WHO) and the Base Nationale de PharmacoVigilance of patient treated by ICI, with a chronology compatible with the drug toxicity	Drug: Immune checkpoint inhibitor Immune checkpoint inhibitor targeting either PD-1, PD-L1 or CTLA-4, and included in the following list (ATC classification) as a monotherapy or in combination: Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32).

Arm

Intervention/Treatment

Adverse drug reaction induced by immune checkpoint inhibitors

Case reported in the World Health Organization (WHO) and the Base Nationale de PharmacoVigilance of patient treated by ICI, with a chronology compatible with the drug toxicity

Drug: Immune checkpoint inhibitor

Immune checkpoint inhibitor targeting either PD-1, PD-L1 or CTLA-4, and included in the following list (ATC classification) as a monotherapy or in combination: Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32).

Outcome Measures

Primary Outcome Measures

Adverse drug reactions induced by ICIs and reported in the World Health Organization (WHO) or the Base Nationale de Pharmacovigilance (BNPV) [Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018]
Identification and report of cases of adverse events associated with ICIs. Drugs investigated are ICIs: Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32).

Secondary Outcome Measures

Causality assessment of reported adverse drug reaction according to the WHO system [Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018]
Description of the type of adverse drug reaction depending on the category of ICIs [Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018]
Description of the other immune related adverse events concomitant to the adverse drug reaction induced by ICIs [Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018]
Description of the duration of treatment when the toxicity happens (role of cumulative dose) [Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018]
Description of the drug-drug interactions associated with adverse events [Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018]
Description of the pathologies (cancer) for which the incriminated drugs have been prescribed [Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018]
Description of the population of patients having adverse event [Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Case reported in the World Health Organization (WHO) database and Base Nationale de Pharmacovigilance (BNPV) of individual safety case reports to 01/05/2018
Adverse events reported
Patients treated with ICIs, in monotherapy or combination, included in the ATC: Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32).