A Phase 2 Open-label Single-arm Trial of JAK1 Inhibitor for the Treatment of Large Inflammatory Hepatocellular Adenomas

NCT06490757 | Recruiting Phase 2

• 1 other identifier: APHP220916
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Inflammatory Hepatocellular Adenoma

Keywords

Hepatocellular adenoma; Inflammatory; JAK STAT pathway

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Radiological response using RECIST 1.1 and at 3 months and 6 months

  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

  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

  6 months and 24 months

• Incidence of adverse events related to the experimental treatment (baracitinib)

  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

  3 months and 6 months

Study Arms (1)

Ancillary study

OTHER

PET CT with 18 FDG will be performed in 12 patients in selected centers (Avicenne hospital, Beaujon hospital, Henri Mondor hospital, Bordeaux hospital, Paul brousse hospital, Saint Antoine hospital with nuclear medicine department available and should be done at baseline and 3 months (+/- one week).

Drug: Baricitinib

Interventions

Baricitinib DRUG

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.

Also known as: fluorodésoxyglucose (18F)- Positron Emission Tomography (PET)

Ancillary study

Eligibility Criteria

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

You may qualify if:

• Women (or male with inflammatory HCA considered as non resectable whatever the size of the HCA)
• Written informed consent for participation in study
• Histologically proven hepatocellular adenoma (confirmed by a centralized reviewing) with available FFPE
• At least one HCA of inflammatory subtype confirmed at histology and immunohistochemistry (CRP or SAA immunohistochemistry) by a centralized reviewing
• At least one HCA of more than 5 cm at imaging of inflammatory subtype (if the HCA of more than 5 cm is not the same HCA proved as inflammatory at histology this HCA should harbored the same imaging features than the HCA with available histology) for women.
• Diagnosed at histology over the last 5 years
• Absence of desire of pregnancy while treated by baricitinib and for at least 4 weeks following the last dose of investigational product
• Females of childbearing potential should have a contraception (without estrogen) when engaging in sexual intercourse with a male partner while treated by baricitinib and for at least 4 weeks following the last dose of investigational product. In case of oral contraception, patients should have been using it for a minimum of one month before the beginning of the treatment. A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
• Male when engaging in sexual intercourse with a female partner shoud have a contraception while treated by baricitinib and for at least 4 weeks following the last dose of investigational product A man is considered fertile after puberty unless permanently sterile by bilateral orchiectomy
• Coverage for medical insurance

You may not qualify if:

• \< 18 years old and \> 65 years old
• Pregnancy or breastfeeding woman
• Patient on AME (state medical aid)
• Have screening electrocardiogram (ECG) abnormalities that, in the opinion of the investigator or the sponsor, are clinically significant and indicate an unacceptable risk for the patient's participation in the study.
• Thrombocytopenia \< 100 000/mm3
• Neutropenia \< 1200/mm3
• Lymphopénia \< 750/mm3
• Anemia \< 9 g/dl
• Concomitant use of immunosuppressive treatment such as methotrexate, azathioprine, mycophenolate (at the exception of corticosteroid)
• ASAT \> 5 times upper fold of the normal or ALAT \> 5 times upper fold of the normal or total bilirubin \> upper 1.5 fold of the normal
• hepatic impairment defined by Child Pugh B or C
• Have evidence of active tuberculosis as documented by medical history, clinical symptoms, and abnormal chest x-ray at screening together with positive quantiferon or T spot test or positive culture
• Renal impairment with estimated creatinine clearance \< 50 ml/mn (Cockroft and Gault formula)
• Have had any major surgery within 8 weeks prior to screening or will require major
• surgery during the study that, in the opinion of the investigator in consultation with the principal investigator, would pose an unacceptable risk to the patient.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

NAULT

Bobigny, 93000, France

RECRUITING

Related Publications (25)

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MeSH Terms

Conditions

Adenoma, Liver Cell

Interventions

baricitinib

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Jean-Charles NAULT, PUPH

  Assistance Publique des Hôpitaux de Paris (APHP)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jean Charles NAULT, PUPH

CONTACT

00336 10 67 94 61; jean-charles.nault@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2024
• First Posted: July 8, 2024
• Study Start: October 2, 2024
• Primary Completion (Estimated): September 2, 2028
• Study Completion (Estimated): September 2, 2028
• Last Updated: December 26, 2025

Record last verified: 2025-10

Locations

FR (1)