Checkpoint Inhibitor-induced Liver Injury
ChILI
1 other identifier
observational
160
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for all trials
Started Oct 2020
Longer than P75 for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 2, 2020
CompletedFirst Posted
Study publicly available on registry
July 20, 2020
CompletedStudy Start
First participant enrolled
October 13, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2026
March 24, 2026
September 1, 2025
5.7 years
July 2, 2020
March 23, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Incidence of checkpoint inhibitor-induced liver injury (ChILI) and other immune-mediated adverse reactions
3 years
Identify novel biomarkers associated with the diagnosis of ChILI
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
Study Arms (2)
ChILI
Patients who are already on CPI therapy and have developed liver injury
Control
Patients with cancer who are starting on checkpoint inhibitors
Interventions
Biological samples (blood, urine, stool). Liver tissue will be obtained from ChILI group when clinically indicated
Eligibility Criteria
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).
You may qualify if:
- 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:
- 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
- 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.
You may not qualify if:
- 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).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Nottinghamlead
- Pfizercollaborator
Study Sites (1)
University of Nottingham
Nottingham, NG72RD, United Kingdom
Related Publications (1)
Ji C, Kumpf S, Qian J, Federspiel JD, Sheehan M, Capunitan D, Atallah E, Astbury S, Arat S, Oziolor E, Ocana MF, Ramaiah SK, Grove J, Aithal GP, Lanz TA. Transcriptomic and proteomic characterization of cell and protein biomarkers of checkpoint inhibitor-induced liver injury. Cancer Immunol Immunother. 2025 May 3;74(6):190. doi: 10.1007/s00262-025-04033-z.
PMID: 40317333DERIVED
Biospecimen
* Collection and storage of biological samples (blood, urine, stool) from patients with ChILI at three-time points (the day of liver injury, 1 week, and 1 month after). The investigators will perform a liver biopsy when it is clinically indicated. * Collection and storage of biological samples (blood, urine, and stool) from control patients at two-time points (before starting CPIs and 6 to14 weeks after commencing treatment)
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 2, 2020
First Posted
July 20, 2020
Study Start
October 13, 2020
Primary Completion (Estimated)
June 30, 2026
Study Completion (Estimated)
June 30, 2026
Last Updated
March 24, 2026
Record last verified: 2025-09