Ebastine for Adjuvant Treatment of Tumor Budding-Positive Liver Cancer After Surgery

Official title

A Single-Arm Study of Ebastine as Adjuvant Therapy in Patients With Tumor Budding-Positive Hepatocellular Carcinoma After Curative Hepatectomy

Overview

This study evaluates ebastine, an FAK (focal adhesion kinase) inhibitor, as adjuvant therapy to reduce the risk of recurrence in patients with hepatocellular carcinoma (HCC) who have undergone curative hepatectomy and whose tumors show a histopathological feature known as tumor budding, which is associated with a higher risk of postoperative recurrence. Ebastine is a second-generation antihistamine approved for allergic conditions. Preclinical studies have shown that ebastine also inhibits FAK signaling, a pathway implicated in tumor invasion, epithelial-mesenchymal transition, and recurrence. This study investigates whether administering ebastine after surgery can lower the recurrence risk associated with tumor budding-positive HCC. All enrolled participants will receive ebastine as adjuvant treatment following hepatectomy. The primary endpoint is the 1-year recurrence-free survival (RFS) rate. Secondary endpoints include 2-year RFS, overall survival, and safety. All participants in this study will receive ebastine as adjuvant (after-surgery) treatment. Researchers will monitor whether the cancer stays away for at least one year after surgery (recurrence-free survival), as well as overall survival and any side effects.

Detailed description

Hepatocellular carcinoma (HCC) remains associated with a high rate of recurrence following curative hepatectomy, and tumor budding-a histopathological feature characterized by isolated single cells or small clusters of tumor cells at the invasive front-has been increasingly recognized as an independent adverse prognostic factor associated with epithelial-mesenchymal transition (EMT), local invasion, and early recurrence in multiple solid tumors, including HCC.

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays a central role in tumor cell adhesion, migration, invasion, and the EMT process that underlies tumor budding. FAK is frequently overexpressed and hyperactivated in HCC tissue and has been implicated in promoting a fibrotic, immunosuppressive tumor microenvironment that supports tumor progression and treatment resistance.

Ebastine, a second-generation H1-antihistamine widely used for allergic rhinitis and urticaria with a well-characterized long-term safety profile, has recently been identified through drug-repurposing research as a small-molecule inhibitor of FAK. Preclinical studies have demonstrated that ebastine binds the tyrosine kinase domain of FAK, blocking autophosphorylation at Y397 and Y576/577 residues, thereby attenuating downstream FAK-mediated signaling (including JAK2/STAT3 and MEK/ERK pathways) that drives tumor stem-cell-like properties, invasion, and metastasis in several solid tumor models, including triple-negative and HER2-positive breast cancer.

Given the mechanistic link between FAK signaling and tumor budding, and the favorable safety and tolerability profile of ebastine at its approved dose range, this study proposes to evaluate ebastine as an adjuvant therapy specifically in patients with tumor budding-positive HCC following curative hepatectomy-a population at elevated risk of early recurrence for whom effective, well-tolerated adjuvant options remain limited.

Interventions

• Drug Ebastine
  Ebastine will be administered orally at 20 mg once daily for 12 months as adjuvant therapy, beginning within 4 to 6 weeks after curative-intent hepatectomy in patients with histologically confirmed tumor budding-positive hepatocellular carcinoma.

Primary outcome measures

• 1-Year Recurrence-Free Survival (RFS) Rate [Time frame: 1 year after surgery]

Secondary outcome measures (3)

• 2-Year Recurrence-Free Survival (RFS) Rate [Time frame: 2 years after surgery]
• Overall Survival (OS) [Time frame: Through study completion, approximately 3 years]
• Incidence of Treatment-Emergent Adverse Events [Time frame: From first dose of ebastine through 30 days after last dose]

Eligibility criteria

Inclusion criteria

• Age is ≥18 years old, male or female;
• Histologically confirmed as hepatocellular carcinoma without metastasis;
• Tumor budding is positive
• Life expectancy of at least 12 weeks;

Exclusion criteria

• Hepatocellular carcinoma that cannot be surgically resected
• Received radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc. before surgery
• Pregnant or lactating women
• Subjects with other malignant tumors;
• Subjects who are considered unsuitable to participate in this cohort study by the investigator;
• Subjects who refuse to enroll or do not sign the informed consent form;
• Subjects with incomplete medical record information (including gender, age, diagnostic information, imaging (and) or pathological diagnosis results, other demographic data, etc.).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07734766 · XJTUSAH-TB-Z009

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗