Clinical trial NCT06311942: Triple vs. Dual Adjuvant Therapy Following Liver Resection for HCC.
Official title: Effectiveness of Triple Versus Dual Adjuvant Therapy in VETC-positive Population Following Liver Resection for HCC: a Prospective Multicenter Cohort Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: HCC
Keywords: HCC
Adjuvant therapy
VETC
HAIC
Lenvatinib
PD-1 inhibitors
Lead sponsor: Tongji Hospital
Sponsor class: OTHER
First posted: 2024-03-15
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 One of our unpublished retrospective studies found that VETC-positive patients receiving PD-1 monoclonal antibody was not effective in improving prognosis, however, PD-1 inhibitor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.

Eligibility criteria: 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.

Primary outcomes:
measure: DFS
timeFrame: 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 outcomes:
measure: OS
timeFrame: From date of include in this research until the date of death from any cause, whichever came first, assessed up to 60 months
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
state: Hubei
Study officials:
affiliation: Tongji Hospital
name: xiaoping Chen
role: PRINCIPAL_INVESTIGATOR
References: