Steroid Sparing in Immune Related Hepatitis (irH)

NCT05345847 | Recruiting DMC

• 1 other identifier: IMPACT 7.0
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hepatitis Immune

Keywords

immune related hepatitis; steroid sparing

Outcome Measures

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

  12 weeks

Secondary Outcomes (5)

• Safety of Steroid Sparing Strategy

  1 year

• Total steroid usage

  1 year

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

  1 year

• Re-initiation of immune checkpoint inhibitor therapy.

  1 year

• The time elapsed between randomization and tumor progression (radiographically or clinically) or death from any cause

  1 year

Study Arms (2)

1- Active Surveillance

EXPERIMENTAL

Active surveillance with rescue corticosteroids

Other: Active Surveillance

2- Early initiation of steroid (Standard)

ACTIVE COMPARATOR

Early intervention with high-dose steroids

Other: Early initiation

Interventions

Active Surveillance OTHER

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

1- Active Surveillance

Early initiation OTHER

Immediate start of high-dose steroids

2- Early initiation of steroid (Standard)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Absence of any condition hampering compliance with the study protocol and follow- up schedule; those conditions should be discussed with the patient before registration in the trial.
• Assessment by the Roussel Uclaf Causality Assessment Method (RUCAM) ≥6 showing probable relationship between ICI and liver injury (appendix)

You may not qualify if:

• 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.
• Previous use of targeted therapies for treatment of malignancy (e.g. BRAF, MEK, EGFR, and VEGF inhibitors) or current treatment with chemotherapy
• Present use of warfarin.
• Diagnosis of immunodeficiency.
• Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (CTCAEv5.0 Grade ≥ 3).
• Other severe acute or chronic medical conditions including inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Sponsors & Collaborators

• AHS Cancer Control Alberta: lead

Study Sites (1)

Arthur J.E. Child Comprehensive Cancer Centre

Calgary, Alberta, T2N 5G2, Canada

RECRUITING

MeSH Terms

Interventions

Watchful Waiting

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration

Study Officials

• Omar Khan, MD

  AHS Cancer Control Alberta

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Omar F Khan, MD

CONTACT

(587) 231-5082; Omar.Khan@cancercarealberta.ca

Amy A

CONTACT

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2022
• First Posted: April 26, 2022
• Study Start: December 8, 2025
• Primary Completion (Estimated): February 8, 2028
• Study Completion (Estimated): February 8, 2029
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)