Adjuvant Sintilimab Plus Lenvatinib for HCC Characterized With VETC Following Liver Resection

Adjuvant Sintilimab Plus Lenvatinib for HCC Characterized With VETC Following Liver Resection: A Multicenter Prospective Study

Vessels that encapsulate tumor clusters (VETC) are a novel invasive metastatic factor in hepatocellular carcinoma (HCC), operating independently of the epithelial-mesenchyme transition (EMT). The presence of VETC is associated with a higher rate of postoperative recurrence in HCC patients, indicating a more aggressive biological behavior.Improving the prognosis for VETC-positive patients is a critical issue in clinical oncology.

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatocellular Carcinoma (HCC)
• Intervention / Treatment: Drug: Sintilimab; Drug: Lenvatinib

Detailed Description

Previous studies have established that VETC is a novel mode of metastasis, independent of EMT, and may be associated with immune suppression and poor prognosis. Numerous retrospective studies have found that patients with VETC positivity have higher rates of postoperative recurrence and distant metastasis. How to improve the surgical prognosis for VETC-positive patients remains to be explored. Currently, there are no published studies on how to improve the prognosis for this group of individuals. One of our unpublished retrospective studies found that treatment with PD-1 monoclonal antibodies does not effectively improve the prognosis for VETC-positive patients. However, the combination of PD-1 monoclonal antibodies with lenvatinib can effectively reduce postoperative recurrence and improve prognosis in VETC-positive patients. Therefore, we have designed this multicenter, randomized controlled trial to explore the efficacy and safety of lenvatinib in combination with sintilimab in VETC-positive HCC.

• Study Type: Interventional
• Enrollment (Estimated): 234
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wanguang Zhang; Phone Number: 13886195965; Email: wgzhang@tjh.tjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18-75 years;

  • No previous local or systemic treatment for hepatocellular carcinoma;

    • Child-Pugh liver function score ≤ 7; ④ECOG PS 0-1; ⑤BCLC stage 0-C, underwent R0 resection and confirmed by pathology as hepatocellular carcinoma; ⑥No major systemic diseases, immunodeficiency diseases, etc.; ⑦CD34 immunohistochemical staining confirms the presence of VETC in the intratumoral vascular pattern (part or all of the field of view)

Exclusion Criteria:

• Pregnant or breastfeeding women;

  • Recurrent HCC, distant metastasis or other systemic tumors;

    • Vascular invasion involving the mesenteric vein, main portal vein, hepatic vein or inferior vena cava;

      • History of gastrointestinal bleeding within the past 4 weeks;

        • Active infection; ⑥Other significant clinical and laboratory abnormalities that affect safety evaluation; ⑦Inability to follow the study protocol, receive treatment or follow-up as scheduled

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adjuvant group; Patients in the adjuvant therapy group received PD-1 monoclonal antibody with Lenvatinb adjuvant therapy after liver resection.	Drug: Sintilimab; Patient receives first adjuvant sintilimab 2-4 weeks postoperatively, 200 mg IV, every 21 days for a total of 8 cycles; Drug: Lenvatinib; lenvatinib is initiated orally(12 mg for body weight >= 60kg, 8 mg for body weight < 60kg daily), 2-4 weeks postoperatively for 6 months.
No Intervention: Control group; The control group patients did not receive any intervention and were actively monitored after surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival	DFS defined as time to recurrence or death after surgery.	From date of include in this research until the date of first documented recurrence or date of death from any cause, whichever came first, assessed up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	The incidence and severity of adverse events (AEs) and serious adverse events (SAEs) as assessed by CTCAE v5.0	Baseline up to 60 months
Overall survival	OS defined as time to death from any cause after surgery.	From date of include in this research until the date of death from any cause, whichever came first, assessed up to 60 months

Collaborators and Investigators

• Sponsor: Wan-Guang Zhang

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2025
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: July 11, 2025
• First Submitted That Met QC Criteria: July 11, 2025
• First Posted (Actual): July 22, 2025

Study Record Updates

• Last Update Posted (Actual): July 22, 2025
• Last Update Submitted That Met QC Criteria: July 11, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: HCC; Recurrence; Lenvatinib; PD-1; VETC
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Lenvatinib
• Other Study ID Numbers: CHALLENGE-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No