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

NCT ID: NCT06311942

Last Updated: 2024-05-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-01
• Study Completion Date: 2028-12-31

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 One of our unpublished retrospective studies found that VETC-positive patients receiving PD-1 monoclonal antibody was not effective in improving prognosis, however, PD-1 inhibitor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

Conditions

HCC

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Triple adjuvant therapy group

Patients in the triple adjuvant therapy group received HAIC in combination with PD-1 inhibitors and lenvatinib adjuvant therapy.

Group Type: EXPERIMENTAL

HAIC plus PD-1 inhibitors plus lenvatinib

Intervention Type: DRUG

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.

Dual adjuvant therapy group

Patients in the Dual adjuvant therapy group received PD-1 inhibitors combined lenvatinib adjuvant therapy.

Group Type: ACTIVE_COMPARATOR

PD-1 inhibitors plus lenvatinib

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Non; Non

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chen Xiaoping

OTHER

Sponsor Role: lead

Responsible Party

Chen Xiaoping

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

xiaoping Chen

Role: PRINCIPAL_INVESTIGATOR

Tongji Hospital

Locations

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

Wuhan, Hubei, China

Site Status: RECRUITING

Countries

China

Central Contacts

WanGuang Zhang

Role: CONTACT

wgzhang@tjh.tjmu.edu.cn

+8613886195965

Facility Contacts

WanGuang Zhang

Role: primary

wgzhang@tjh.tjmu.edu.cn

+8613886195965

Other Identifiers

Precision AT-02

Identifier Type: -

Identifier Source: org_study_id