Triple vs. Dual Adjuvant Therapy Following Liver Resection for HCC.

Phase 4

Recruiting

• Conditions: HCC
• Interventions: Drug: HAIC plus PD-1 inhibitors plus lenvatinib; Drug: PD-1 inhibitors plus lenvatinib

• Registration Number: NCT06311942
• Lead Sponsor: Chen Xiaoping

Brief Summary

Vessels that encapsulate tumor clusters (VETC) is an invasive metastatic factor in HCC independent of the epithelial mesenchyme transition (EMT), and VETC-positive patients have a higher rate of postoperative recurrence. What can be done to improve the surgical prognosis of this group of patients needs to be continuously explored.

Detailed Description

Previous studies have identified VETC as a new metastatic pattern independent of EMT that may be associated with immunosuppression as well as poor prognosis. Multiple retrospective studies find higher rates of postoperative recurrence, distant metastasis in VETC-positive patients. How to improve surgical prognosis in VETC-positive patients needs to be explored. In recent years, adjuvant immunotherapy (sintilimab) and adjuvant immunotherapy combined with targeted therapy (T+A) have been shown to be effective in improving the surgical prognosis. There are no published studies on how to improve prognosis for VETC-positive population. One of our unpublished retrospective studies found that VETC-positive patients receiving PD-1 monoclonal antibody was not effective in improving prognosis, however, PD-1 inhibitor combined with lenvatinib reduces recurrences significantly. In addition, some studies have also found that postoperative adjuvant hepatic artery infusion chemotherapy (HAIC) is also potentially useful in improving surgical prognosis. It is not clear whether triple therapy can further reduce recurrence in these tumors, which have highly aggressive characteristics.

Study Timeline

• Study First Submitted: 2024-03-09
• Study First Submitted QC: 2024-03-09
• Study First Posted: 2024-03-15
• Study Start: 2024-04-01
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-05
• Last Update Posted: 2024-05-07
• Primary Completion: 2027-12-31
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

1. Aged 18-75.
2. No previous local or systemic treatment for hepatocellular carcinoma.
3. Child-Pugh liver function score ≤ 7.
4. ECOG PS 0-1.
5. No serious organic diseases of the heart, lungs, brain, kidneys, etc.
6. Pathologic type is hepatocellular carcinoma .
7. Confirmation of the presence of VETC vascular pattern by CD34 immunohistochemical staining.

Exclusion Criteria

1. Pregnant and lactating women.
2. Suffering from a condition that interferes with the absorption, distribution, metabolism, or clearance of the study drug (e.g., severe vomiting, chronic diarrhea, intestinal obstruction, impaired absorption, etc.).
3. A history of gastrointestinal bleeding within the previous 4 weeks or a definite predisposition to gastrointestinal bleeding (e.g., known locally active ulcer lesions, fecal occult blood ++ or more, or gastroscopy if persistent fecal occult blood +) that has not been targeted, or other conditions that may have caused gastrointestinal bleeding (e.g., severe fundoplication/esophageal varices), as determined by the investigator.
4. Active infection.
5. Other significant clinical and laboratory abnormalities that affect the safety evaluation.
6. Inability to follow the study protocol for treatment or follow up as scheduled.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Triple adjuvant therapy group	HAIC plus PD-1 inhibitors plus lenvatinib	Patients in the triple adjuvant therapy group received HAIC in combination with PD-1 inhibitors and lenvatinib adjuvant therapy.
Dual adjuvant therapy group	PD-1 inhibitors plus lenvatinib	Patients in the Dual adjuvant therapy group received PD-1 inhibitors combined lenvatinib adjuvant therapy.

Primary Outcome Measures

Name	Time	Method
DFS	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	DFS defined as time to recurrence or death after surgery.

Secondary Outcome Measures

Name	Time	Method
OS	From date of include in this research until the date of death from any cause, whichever came first, assessed up to 60 months	OS defined as time to death from any cause after surgery.

Trial Locations

Locations (1)

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; 🇨🇳 Wuhan, Hubei, China