Checkpoint Inhibitor-induced Liver Injury (ChILI)

November 1, 2022 updated by: University of Nottingham

Checkpoint Inhibitor-induced Liver Injury Study (ChILI)

In this multi-center prospective observational study, the investigators plan to identify the incidence and risk factors for checkpoint inhibitor-induced liver injury and characterize biochemical, genetic, immunological, and histological features associated with it.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Checkpoint inhibitor-induced liver injury (ChILI) is a new incompletely understood category of hepatotoxicity which is distinct from other types of drug-induced liver injury (DILI) such as direct or idiosyncratic DILI. The data regarding the incidence and risk factors is lacking. Therefore, 'in-depth phenotyping' together with data from the control group exposed to checkpoint inhibitors (CPI) is necessary to develop refined algorithms incorporating CPI-related factors, host genetic and environmental risk factors that would enable pre-empting ChILI.

The aim of the study is to enroll two deeply phenotyped cohorts (patients who developed ChILI and patients who are starting checkpoint inhibitors) and obtain biological samples at multiple time points.

Study Type

Observational

Enrollment (Anticipated)

160

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

ChILI group:

Adults with cancer receiving checkpoint inhibitors (CTLA-4, PD-1 or PD L1 inhibitor) as monotherapy or combination (without chemotherapy) and developed acute liver injury secondary to checkpoint inhibitor.

Control Group:

Patients with malignant melanoma, renal cell carcinoma, non-small cell lung cancer or any other cancer, receiving single or combination therapy using checkpoint inhibitors (CPIs).

Description

Inclusion Criteria:

Both patient groups and control group:

• Able to give written informed consent OR Potential participants who have developed encephalopathy related to ChILI as a response to checkpoint inhibitor therapy, who lack the capacity to give written informed consent and have a consultee (personal or nominated) - for ChILI patient group only

ChILI group:

Patients who developed checkpoint inhibitor-induced liver injury and meet the following criteria:

  1. Meets one of the following analytical thresholds at enrolment (visit 1)

    • Alanine transaminase (ALT) exceeding 5 times the upper limit of normal (ULN) OR
    • ALT exceeding 3 times ULN plus bilirubin exceeding 2 times ULN OR
    • Alkaline phosphatase (ALP) exceeding 2 times ULN with accompanying elevations of gamma-glutamyl transferase in the absence of known bone metastases driving the rise in ALP level
  2. Absence of other known causes of liver injury after detailed investigations

Patients who developed ChILI but did not meet the above criteria at enrolment or who were found to have a different cause for their liver injury after further investigations will be excluded from the analysis

Control group:

Consecutive patients with cancer who have a clinical indication to start checkpoint inhibitors. A small proportion of patients will develop ChILI following their checkpoint inhibitor treatment and will be classified as cases.

Exclusion Criteria:

  • Patients who are treated with cytotoxic chemotherapy concurrently with checkpoint inhibitors.
  • On the judgment of chief investigator that the person has certain alternative explanations to the acute event (rather than ChILI).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
ChILI
Patients who are already on CPI therapy and have developed liver injury
Diagnostic test: Obtaining biological samples
Biological samples (blood, urine, stool). Liver tissue will be obtained from ChILI group when clinically indicated
Control
Patients with cancer who are starting on checkpoint inhibitors
Diagnostic test: Obtaining biological samples
Biological samples (blood, urine, stool). Liver tissue will be obtained from ChILI group when clinically indicated

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of checkpoint inhibitor-induced liver injury (ChILI) and other immune-mediated adverse reactions
Time Frame: 3 years
3 years
Identify novel biomarkers associated with the diagnosis of ChILI
Time Frame: 3 years
The investigators plan assessment of proposed circulating biomarkers including cytokines, microRNAs (miR-122, miR-4270 and miR-4463), total cytokeratin 18 (K18), macrophage colony-stimulating factor receptor (MCSFR), and any others identified in subsequent publications and measure their diagnostic and prognostic accuracy using the area under the receiver operating curve (AUROC).
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Nottingham

Collaborators

Pfizer

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 13, 2020

Primary Completion (Anticipated)

August 1, 2023

Study Completion (Anticipated)

August 1, 2023

Study Registration Dates

First Submitted

July 2, 2020

First Submitted That Met QC Criteria

July 14, 2020

First Posted (Actual)

July 20, 2020

Study Record Updates

Last Update Posted (Actual)

November 2, 2022

Last Update Submitted That Met QC Criteria

November 1, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20034 (Other Identifier: City of Hope Medical Center)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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