A Phase 2 Open-label Single-arm Trial of JAK1 Inhibitor for the Treatment of Large Inflammatory Hepatocellular Adenomas
NCT Number: NCT06490757
Acronym: JAKIH
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Inflammatory Hepatocellular Adenoma
Interventions: DRUG: Baricitinib
Sponsor: Assistance Publique - Hôpitaux de Paris
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 25
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09-02
Completion Date: 2028-09-02

Summary:
Hepatocellular adenomas (HCA) are tumors rare benign hepatic infections that develop on a liver normal and in young women taking a estrogen-based contraception. The main molecular subgroup of AHCs is the AHC subgroup inflammatory, which are associated with a risk of bleeding from the tumor and malignant transformation. Therefore, most of women with large inflammatory AHC (\>5 cm) require liver resection which can be associated with morbidity and aesthetic problems, and rarely to mortality. On the basis of the knowledge of the molecular classification of AHCs humans and preclinical data testing the JAK1/2 inhibitors, we hypothesize that a short duration of treatment with the inhibitor of JAK1/2 (baricitinib) may be effective in patients with large inflammatory AHC size.

Primary Outcome Measures: The principal outcome is to demonstrate that the combination of an experimental procedure to the standard of care lead to a significant decrease in size of large inflammatory HCA at imaging, The primary endpoint will be assessed at 6 months by comparing the liver MRI with contrast agent at baseline with the liver MRI with contrast agent at 6 months. An external independent reviewing will be performed separately by two radiologists that will classify the radiological response according to RECIST 1.1 criteria at 6 months in complete response, partial response, stable disease and progressive disease., 6 month
Secondary Outcome Measures: Radiological response using RECIST 1.1 and at 3 months and 6 months, Proportion of overall radiological response (partial and complete response), stable disease, and progressive disease using RECIST 1.1 criteria at 3 months and 6 months MRI, 3 months and 6 months|Decrease in size of the target lesions below 5 cm at 3 months and 6 months at imaging using RECIST 1.1 criteria, Proportion of target lesions (inflammatory HCA \> 5 cm) showing a decrease in size below 5 cm at 3 months and 6 months MRI using RECIST 1.1 thus modified RECIST criteria at MRI, 3 months and 6 months|Need for liver surgery of HCA at 6 months and 24 months (end of the follow-up) due to absence of sufficient decrease in size of the tumor under baricitinib, Proportion patients treated by liver surgery for HCA at 6 months and the end of the 24 months follow-up, 6 months and 24 months|Incidence of adverse events related to the experimental treatment (baracitinib), Adverse events within the 24 months of the study a) all adverse events b) occurrence of zona c) cancer d) major adverse cardiovascular events (MACE), Inclusion at 24 month|In patients with multiple HCA, radiological response using RECIST 1.1 at 3 months and 6 months focusing of HCA at the exclusion of the IHCA confirmed at histology, In patients with multiple HCA, the proportion patients with complete response, partial response, stable disease and progressive disease focusing on other HCA excluding the inflammatory HCA confirmed at histology according to RECIST 1.1 criteria at MRI at 3 months and 6 months., 3 months and 6 months|Symptomatic HCA bleeding during follow-up, Proportion of symptomatic bleeding of HCA during follow-up, follow-up (D15, M1, M3, M6, M12; M18 and M24)|Incidence of malignant transformation of hepatocellular adenomas into hepatocellular carcinoma during the study, Proportion of malignant transformation in HCC during follow-up at histology and confirmed by a multidisciplinary tumor board, follow-up (D15, M1, M3, M6, M12; M18 and M24)|Occurrence of increase in tumor size or number after discontinuation of baricitinib using RECIST 1.1 criteria during follow-up, Proportion of patients with a progressive disease between baricitinib discontinuation (6 months) and 24 months of follow-up using RECIST 1.1 criteria at imaging, baricitinib discontinuation (6 months) to 24 months|Occurrence of increase in tumor size up to 5 cm after discontinuation of baricitinib using RECIST 1.1 criteria during follow-up, Proportion of patients with an increase in tumor size below 5 cm between baricitinib discontinuation (6 months) and 24 months at MRI, baricitinib discontinuation (6 months) to 24 months|Incidence of post-operative adverse events in cases requiring hepatic surgery for hepatocellular adenoma during follow-up, Proportion of post-operative adverse events (using the Dindo-Clavien Classification) if liver surgery is required during follow-up, follow-up (D15, M1, M3, M6, M12; M18 and M24)