Checkpoint Inhibitor-induced Liver Injury

NCT04476563

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Immune-Mediated Hepatitis
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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).

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Immune-Mediated HepatitisCheckpoint Inhibitor-induced Liver Injury
NCT04476563
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title Checkpoint Inhibitor-induced Liver Injury
Official Title Checkpoint Inhibitor-induced Liver Injury Study (ChILI)
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.
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
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
  • 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)
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).

Condition Immune-Mediated Hepatitis
Intervention Diagnostic Test: Obtaining biological samples
Biological samples (blood, urine, stool). Liver tissue will be obtained from ChILI group when clinically indicated
Study Groups/Cohorts
  • ChILI
    Patients who are already on CPI therapy and have developed liver injury
    Intervention: Diagnostic Test: Obtaining biological samples
  • Control
    Patients with cancer who are starting on checkpoint inhibitors
    Intervention: Diagnostic Test: Obtaining biological samples
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Not yet recruiting
Estimated Enrollment
 (submitted: July 14, 2020)
160
Original Estimated Enrollment Same as current
Estimated Study Completion Date August 2023
Estimated Primary Completion Date August 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria

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).
Sex/Gender
Sexes Eligible for Study:All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Guruprasad Padur Aithal, MBBS, FRCP, PhD0115 823 1074[email protected]
Listed Location Countries Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number NCT04476563
Other Study ID Numbers 20034
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party University of Nottingham
Study Sponsor University of Nottingham
Collaborators Pfizer
Investigators Not Provided
PRS Account University of Nottingham
Verification Date June 2020