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

Official title

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

Overview

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.

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 One of our unpublished retrospective studies found that treatment with PD-1 monoclonal antibodies does not effectively improve the prognosis for VETC-positive patients.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.

Interventions

• 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.

Primary outcome measures

• Disease-free survival [Time frame: 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 (2)

• Overall survival [Time frame: From date of include in this research until the date of death from any cause, whichever came first, assessed up to 60 months]
• Adverse events [Time frame: Baseline up to 60 months]

Eligibility criteria

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

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

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07077798 · CHALLENGE-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗