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

HCC Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06311942
• Other study ID #: Precision AT-02
• Status: Recruiting
• Phase: Phase 4
• Start date: April 1, 2024
• Est. completion date: December 31, 2028

Study information

• Verified date: May 2024
• Source: Tongji Hospital
• Contact: WanGuang Zhang
• Phone: +8613886195965
• Email: wgzhang[@]tjh.tjmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 One of our unpublished retrospective studies found that VETC-positive patients receiving PD-1 monoclonal antibody was not effective in improving prognosis, however, PD-1 inhibitor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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 31, 2028
• Est. primary completion date: December 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• HCC

Intervention

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.
• 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.

Locations

Country	Name	City	State
China	Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Chen Xiaoping

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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