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.
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, characterized by activation of the pathway JAK/STAT due to mutations in IL6ST, STAT3, FRK, JAK1 or GNAS, with inflammatory infiltrates at histology. Hepatocellular adenomas 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
An ancillary study will be performed in a subgroup of 12 patients to assess the variation of the results of PET-CT with 18FDG from baseline to 3 months. The variation of tumor features assessed by PET-CT with 18FDG after three months of treatment, will be assessed. The median value of the SUV max and tumor to non-tumor ratio of the SUV max value for each HCA lesion between the PET CT with 18FDG performed at baseline and after 3 months of treatment will be assessed.
NAULT
Bobigny, France
RECRUITINGThe 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.
Time frame: 6 month
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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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.
Time frame: 3 months and 6 months
Symptomatic HCA bleeding during follow-up
Proportion of symptomatic bleeding of HCA during follow-up
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: follow-up (D15, M1, M3, M6, M12; M18 and M24)
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