Checkpoint Inhibitor-induced Liver Injury

ConditionImmune-Mediated Hepatitis

Trial statusRecruiting

Trial phaseNot listed

Trial typeObservational

Biological sexAll

Age18+

SponsorUniversity of Nottingham

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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).

Trial 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).

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

Obtaining biological samples
Diagnostic test
Biological samples (blood, urine, stool). Liver tissue will be obtained from ChILI group when clinically indicated

Treatment groups

160 Participants

are divided into 2 treatment groups

Group A: ChILI1 intervention

Group B: Control1 intervention

Trial outcomes

Primary outcomes

Incidence of checkpoint inhibitor-induced liver injury (ChILI) and other immune-mediated adverse reactions

Time frame

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).

Time frame

3 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Nottingham

Lead sponsor

Pfizer

Collaborator

Source ClinicalTrials.gov

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