Immune-related hepatitis induced by immune checkpoint inhibitors in patients with solid tumors Immune-related adverse events (irAEs)
Conditions
Interventions
MMF 1000 mg administered twice daily (total daily dose: 2000 mg) in addition to steroid therapy.
Sponsors
Tatsuya Yoshida
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Diagnosed with a solid cancer by histological or cytological examination 2) Currently receiving or has a prior history of receiving treatment with an ICI 3) No pericardial effusion, pleural effusion, or ascites requiring therapeutic intervention 4) Age>=18 years at the time of registration 5) Performance Status (ECOG) of 0-2 6) Developed Grade >=3 liver dysfunction (ALT elevation) as an irAE caused by ICI, and steroid intervention is deemed necessary by the treating physician 7) Causes other than irAE-related liver dysfunction have been excluded by abdominal ultrasonography or abdominal plain/contrast-enhanced CT performed within 14 days prior to registration the same weekday is acceptable). 8) Laboratory tests performed within 24 hours prior to registration meet all of the following criteria: 1.Neutrophil count >=1,000/mm3 2. Platelet count >=5x10(4)/mm3 3. Hemoglobin >=8.0 g/dL 4. Creatinine =<1.5 mg/dL 5. PT-INR =<2.3 9) Able to take oral medication 10) For women of childbearing potential, the patient agrees to use effective contraception during the protocol treatment period and for at least 90 days after protocol treatment completion, and to refrain from breastfeeding during this period. For males, the patient agrees to use effective contraception during the protocol treatment period and for at least 90 days after protocol treatment completion. 11) Written informed consent for participation in the study has been obtained from the patient.
Exclusion criteria
Exclusion criteria: 1) History of hypersensitivity to MMF 2) Positive for any of the following: HIV antibody, HBs antigen, or HCV-RNA (HCV-RNA is measured only when HCV antibody is positive) 3) HBs antigen-negative, HBs antibody or HBc antibody-positive, and HBV DNA-positive (Patients are not excluded if the HBV DNA level is below the detection limit; however, monitoring must be performed in accordance with the Hepatitis B Treatment Guidelines (2022). 4) Cholangitis requiring drainage procedures (e.g., stent placement) 5) History of receiving steroids or MMF for liver dysfunction due to irAE-related ALT elevation (prior steroid administration for the liver dysfunction that qualifies for this study is permitted) 6) Currently receiving ongoing steroids or MMF for reasons other than irAE-related liver dysfunction (hormone replacement therapy with hydrocortisone or similar agents is permitted) 7) Pregnant or breastfeeding, or women who may be pregnant (women may be enrolled if breastfeeding is discontinued) 8) Presence of psychiatric disorders or symptoms that significantly interfere with daily functioning, making participation in the trial difficult. 9) Deemed ineligible for trial participation by the principal investigator or sub-investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ALT reduction rate on Day 7 after registration | — |
Secondary
| Measure | Time frame |
|---|---|
| ALT reduction rate at Day 3, Day 14, Day 28, Day 84 (3 months), and Day 168 (6 months) after registration/ Proportion of patients with a decrease in ALT grade at Day 3, Day 7, Day 14, Day 28, Day 84 (3 months), and Day 168 (6 months) after registration/ Proportion of patients with ALT Grade 1 or lower at Day 3, Day 7, Day 14, Day 28, Day 84 (3 months), and Day 168 (6 months) after registration/ Proportion of patients with ALT Grade 2 or lower at Day 3, Day 7, Day 14, Day 28, Day 84 (3 months), and Day 168 (6 months) after registration/ Proportion of patients with a >=30% reduction in ALT from the most recent pre-registration value at Day 3, Day 7, Day 14, Day 28, Day 84 (3 months), and Day 168 (6 months)/ Cumulative proportion of patients with recurrence at Day 3, Day 7, Day 14, Day 28, Day 84 (3 months), and Day 168 (6 months) after registration/ Total steroid dose and duration of steroid treatment administered until the date when steroid therapy for irAE-related liver dysfunction is judged to be completed/ Overall survival (OS)/ Incidence of adverse events and incidence of adverse reactions/ Incidence of serious adverse events, incidence of serious adverse reactions | — |
Contacts
Public ContactNCCH2415 Clinical Trial Coordinating Office
National Cancer Center Hospital
Outcome results
None listed