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

Effectiveness of Triple Versus Dual Adjuvant Therapy in VETC-positive Population Following Liver Resection for HCC: a Prospective Multicenter Cohort Study

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.

Study Overview

• Status: Recruiting
• Conditions: HCC
• Intervention / Treatment: Drug: HAIC plus PD-1 inhibitors plus lenvatinib; Drug: PD-1 inhibitors plus lenvatinib

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 One of our unpublished retrospective studies found that VETC-positive patients receiving PD-1 monoclonal antibody was not effective in improving prognosis, however, PD-1 inhibitor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 Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: WanGuang Zhang; Phone Number: +8613886195965; Email: wgzhang@tjh.tjmu.edu.cn

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
      • Contact: WanGuang Zhang; Phone Number: +8613886195965; Email: wgzhang@tjh.tjmu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

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 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: Triple adjuvant therapy group; Patients in the triple adjuvant therapy group received HAIC in combination with PD-1 inhibitors and lenvatinib adjuvant therapy.	Drug: HAIC plus PD-1 inhibitors plus lenvatinib; Patients in the triple adjuvant therapy group received one cycle of HAIC about a month after liver resection, HAIC was adopted the FOFOLX6 program (Folinic acid+5-fluorouracil+Oxaliplatin). The first cycle of PD-1 monoclonal antibody was administrated 2-4 weeks postoperatively, 200 mg IV, every 21 days for a total of 9 cycles. Lenvatinib was initiated orally 2-4 weeks postoperatively for 6 months.; Other Names: Non
Active Comparator: Dual adjuvant therapy group; Patients in the Dual adjuvant therapy group received PD-1 inhibitors combined lenvatinib adjuvant therapy.	Drug: PD-1 inhibitors plus lenvatinib; The first cycle of PD-1 monoclonal antibody was administrated 2-4 weeks postoperatively, 200 mg IV, every 21 days for a total of 9 cycles. Lenvatinib was initiated orally 2-4 weeks postoperatively for 6 months.; Other Names: Non

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DFS	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
OS	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: Chen Xiaoping
• Investigators: Principal Investigator: xiaoping Chen, Tongji Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: March 9, 2024
• First Submitted That Met QC Criteria: March 9, 2024
• First Posted (Actual): March 15, 2024

Study Record Updates

• Last Update Posted (Actual): May 7, 2024
• Last Update Submitted That Met QC Criteria: May 5, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: HCC; Lenvatinib; HAIC; Adjuvant therapy; PD-1 inhibitors; VETC
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Lenvatinib; Immune Checkpoint Inhibitors
• Other Study ID Numbers: Precision AT-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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