Management of Immune Checkpoint Inhibition-related Hepatitis Using Low-dose Corticosteroids

NCT07167251 | Recruiting

• 1 other identifier: 2025-00696
• Study Type: observational
• Target: 63
• Locations: 2 countries
• Sites: 2

Brief Summary

This study evaluates the effectiveness of low-dose corticosteroids in managing grade 2-3 immune-related hepatitis in cancer patients treated with immune checkpoint inhibitors. It aims to determine whether of 0.5-1miligram per kilogram bodyweight prednisolone is sufficient to manage immune-related hepatitis without the need for dose escalation or additional immunosuppressive therapy.

Conditions

Immune Related Adverse Events; Immune-Mediated Hepatitis; Cancer

Keywords

Immune-related adverse events; Immune checkpoint inhibitor; Immune-related hepatitis; immune-mediated hepatitis

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with resolution of their IR hepatitis CTCAE grade 3 within 8 weeks of onset

  Resoultion is defined as back to baseline or grade 1 without escalation of the corticosteroid dose, without additional immunosuppression and with discontinuation of corticosteroids or reduction to a maximum of 10 mg of Prednisolone

  8 weeks of onset

Secondary Outcomes (10)

• Proportion of patients with resolution of their IR hepatitis CTCAE grade 2 or 3 within 8 weeks of onset

  8 weeks

• Proportion of patients requiring dose escalation of corticosteroids

  Outcome assessed at each visit until end of follow-up (6 months).

• Time to resolution of IR hepatitis

  Outcome assessed at each visit until end of follow-up (6 months).

• Peak dose of corticosteroids

  Outcome assessed at each visit until end of follow-up (6 months).

• Cumulative dose of corticosteroids

  Outcome assessed at each visit until end of follow-up (6 months).

Other Outcomes (2)

• Recruitment rate

  At recruitment completion (last patient enrolled, up to 18 months)

• Retention rate

  At study completion (final follow-up, 6 months after inclusion of the last patient])

Study Arms (2)

Immune-related hepatitis grade 2

Grade 2 hepatitis is defined as an elevation of Aspartate transaminase (AST) and/or Alanine aminotransferase (ALT) levels to 3-5 times the upper limit of normal, in accordance with the guidelines of the European Society for Medical Oncology.

Drug: Low-dose corticosteroids for immune-related hepatitis grade 2

Immune-related hepatitis grade 3

Grade 3 hepatitis is defined as an elevation of Aspartate transaminase and/or Alanine aminotransferase levels to 5-20 times the upper limit of normal, in accordance with the guidelines of the European Society for Medical Oncology.

Drug: Low-dose corticosteroids for immune-related hepatitis grade 3

Interventions

Low-dose corticosteroids for immune-related hepatitis grade 3 DRUG

Prednisolone 0.5-1 mg/kg orally for grade 3 IR-hepatitis; adjusted based on liver function; treatment per local standard of care.

Immune-related hepatitis grade 3

Low-dose corticosteroids for immune-related hepatitis grade 2 DRUG

Hold immunotherapy and reassess liver function at the treating physician's discretion. If liver function tests persistently worsen or continue to rise, consider administering prednisolone at 0.5 mg/kg body weight

Immune-related hepatitis grade 2

Eligibility Criteria

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

Study Population

The target patient population of this study are patients treated with immune checkpoint inhibitors (either as monotherapy with an anti-programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) antibody, or with an anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, or as combination therapy with an PD-1 and CTLA-4 antibody, or an PD-1 and lymphocyte-activation gene 3 (LAG3) antibody) who develop grade 2 or 3 Immune-related hepatitis independently of the treated cancer entity.

You may qualify if:

• Cancer patients aged 18 years or older
• Treatment with a programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) antibody, or a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, or a combination of a PD-1 and CTLA-4 antibody, or a PD-1 and lymphocyte-activation gene 3 (LAG-3) antibody
• Occurrence of immune-related hepatitis grade 2 to 3 (as per judgment of the investigator)
• Ability of the patient to comply with the study procedures (management of immune-related hepatitis)

You may not qualify if:

• Previous Immune-related hepatitis that required systemic therapy
• Treatment for Immune-related hepatitis has already been initiated with high-dose corticosteroids (\>0.5 mg/kg body weight)
• Immune-related hepatitis with bilirubin \> 1.5 ULN or clinical suspicion of cholangitis or elevated INR (beyond baseline)
• Immune-related hepatitis with grade 4 at first presentation
• Prior irAE treated with systemic immunosuppression
• Simultaneous immune-related neurological toxicity or immune-related myocarditis (since these usually have to be treated with high doses of corticosteroids)
• a. Patients with other immune-related adverse events may be included according to the investigator's judgment
• Known liver disease (e.g., autoimmune hepatitis, active hepatitis B, C or E, hemochromatosis, liver cirrhosis Child-Pugh Score B or C, primary biliary cholangitis, primary biliary cirrhosis, Morbus Wilson)
• a. Patients with liver metastasis are eligible
• Patients receiving cancer treatment other than immune checkpoint inhibitors in parallel (e.g., tyrosine kinase inhibitors or chemotherapy).
• a. Patients who have received other cancer treatments in previous cycles are eligible, provided the treating physician does not assume any toxicity from the other medication.
• Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days prior to occurrence of IR hepatitis. Stable corticosteroid doses of \< 10mg prednisone equivalent are allowed.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Royal Marsden NHS Foundation Trust: collaborator
• Odense University Hospital: collaborator
• UMC Utrecht: collaborator

Study Sites (2)

University Hospital Basel

Basel, Canton of Basel-City, 4031, Switzerland

RECRUITING

Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

NOT YET RECRUITING

MeSH Terms

Conditions

Neoplasms

Interventions

Adrenal Cortex Hormones

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Andreas M Schmitt, MD

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andreas M Schmitt, MD

CONTACT

+41 61 265 50 74; andreasmichael.schmitt@usb.ch

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 6 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy Physician

Study Record Dates

• First Submitted: August 25, 2025
• First Posted: September 11, 2025
• Study Start: August 25, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

GB (1); CH (1)