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Steroid Sparing in Immune Related Hepatitis (irH)

ConditionHepatitis Immune
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorAHS Cancer Control Alberta

About this trial

A multi-centre, randomized, non-inferiority trial in patients with irH, randomized to receive either close surveillance with corticosteroid rescue therapy or early high dose corticosteroids.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patients must be 18 years of age, or older on the day of signing informed consent.

Patients must be capable of providing consent to enrolment and treatment.

Patients with a performance status of ECOG 0-2 will be eligible for enrolment.

Patients with histologically confirmed cancer receiving anti-PD1 or anti-PDL1 monoclonal antibody ICI therapy, either alone or in combination with anti-CTLA-4 monoclonal antibody ICI therapy who develop CTCAEv5.0 grade 2 or grade 3 hepatitis that has developed on, or after, ICI therapy and is felt to be treatment related (irH). Patients must be enrolled on trial within 10 days of diagnosis of grade 2 or grade 3 hepatotoxicity.

Disqualifiers

History underlying liver disease, including, but not limited to: hepatitis B, C, autoimmune hepatitis, primary biliary sclerosis, hemochromatosis, primary sclerosis cholangitis, portal vein thrombosis, Budd Chiari syndrome, alcohol induced hepatitis, suspected drug-induced liver injury from other cause (e.g. acetaminophen, antibiotics, statins, methyldopa, non-prescription herbs, see NIH LiverTox website https://livertox.nih.gov for comprehensive list).

If undertaken, liver biopsy supporting a cause of liver dysfunction other than irH

Patients with an indication for systemic immunosuppressive medications or corticosteroids. Patients with CTCAEv5.0 grade ≥2 irAE's other than irH (ie. colitis, pneumonitis, rash, etc.) are not eligible for trial, with the exception of endocrinopathies that are being treated with hormone replacement alone and not systemic immunosuppressive medications or corticosteroids.

Abnormal International Normalization Ratio (INR) at baseline (≥1.5) and bilirubin ≥60, ALT of ≥10X.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Active Surveillance

    Other intervention

    Close monitoring of liver enzymes with steroid rescue strategy (watch and wait approach)

  • Early initiation

    Other intervention

    Immediate start of high-dose steroids

Treatment groups

56 Participants
are divided into 2 treatment groups
Group A: 1- Active SurveillanceExperimental treatment 1 intervention
Group B: 2- Early initiation of steroid (Standard)Active comparator 1 intervention

Trial outcomes

Primary outcomes

1

Resolution of biochemical abnormalities in grade 2 and grade 3 irH at 12 weeks.

The primary objective of this clinical trial is to determine if active surveillance with steroid salvage is a non-inferior strategy in grade 2 and grade 3 irH in patients without evidence of liver dysfunction. Resolution will be defined as improved in irH to grade ≤1. This was chosen as a clinically significant endpoint as it is often used by oncologists to determine if patients may resume ICI therapy. Assessment and grading will be completed by the investigator according to CTCAEv5.0

Time frame
12 weeks

Secondary outcomes

1

Safety of Steroid Sparing Strategy

To evaluate the safety of surveillance strategy based on rates of hospitalization, ICU admission, development of clinically significant liver failure (e.g. decompensated hepatic failure) and death.

Time frame
1 year
2

Total steroid usage

Total steroid usage (defined as the total amount of prednisone or prednisone equivalent in mg required over the study period).

Time frame
1 year
3

Development of immune related adverse events (irAE's) other than irH.

Defined as the emergence of adverse events that were not present at study baseline that are deemed by the investigator to be related to prior use of immune checkpoint inhibitors. Causality will be investigator assessed and graded according to CTCAEv5.0.

Time frame
1 year
4

Re-initiation of immune checkpoint inhibitor therapy.

The proportion of patients in each study arm that are re-treated with an immune checkpoint inhibitor.

Time frame
1 year

Other outcomes

Sponsors and contacts

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

AHS Cancer Control Alberta

Lead sponsor

Source ClinicalTrials.gov
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