NCT06280313

Impact of Splenectomy on the Efficacy of Targeted Therapy and Immunotherapy in Unresectable HCC Patients With Cirrhotic Portal Hypertension

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 60 (estimated)
• Sponsor: Zhiyong Huang · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Currently, the combination of targeted therapy and immunotherapy is the first-line treatment for advanced hepatocellular carcinoma (HCC). However, a subset of HCC patients with severe splenomegaly, splenic hyperfunction, and esophagogastric varices due to liver cirrhosis and portal hypertension may be unable to undergo or sustain the combination therapy, ultimately missing the optimal treatment window. Prior studies have indicated that splenectomy can significantly improve liver function and hepatic reserve in cirrhotic patients. It also addresses splenic hyperfunction and reduces the risk of bleeding from esophagogastric varices by combining splenectomy with devascularization around the cardia. Additionally, splenectomy contributes to the improvement of liver fibrosis and restoration of immune function in cirrhotic patients. This study aims to elucidate the impact of splenectomy on the efficacy of combination targeted and immunotherapy in unresectable HCC patients with cirrhotic portal hypertension, particularly those with poor liver function, significant splenic hyperfunction, and severe esophagogastric varices. The research also seeks to explore whether changes in the tumor immune microenvironment before and after splenectomy can influence the effectiveness of immunotherapy. Ultimately, the goal is to provide therapeutic opportunities for this specific patient population.

Detailed description

This is a single-arm, open-label, observational study assessing the impact of splenectomy on the efficacy of combined targeted and immune therapy in patients with unresectable hepatocellular carcinoma accompanied by cirrhotic portal hypertension. Eligible patients with unresectable hepatocellular carcinoma were enrolled in the trial, and all participants underwent either open or laparoscopic splenectomy, with or without devascularization around the cardia. Starting two weeks post-surgery, patients began intravenous infusion of PD-1 monoclonal antibody, Tislelizumab, at a dosage of 200mg every three weeks. Three weeks post-surgery, patients commenced oral administration of the targeted therapy, Lenvatinib, with a dosage based on body weight: 8mg (≤60kg) or 12mg (\>60kg), once daily. The use of Tislelizumab and Lenvatinib continued until the primary endpoint, which was disease progression, intolerable toxicity reactions, or other criteria specified in the protocol for terminating the study treatment.

Conditions

• Unresectable Hepatocellular Carcinoma

Interventions

Type	Name	Description
COMBINATION_PRODUCT	Splenectomy+Targeted therapy+ Immunotherapy	Eligible patients with unresectable hepatocellular carcinoma accompanied by cirrhotic portal hypertension were enrolled in the trial, and all participants underwent either open or laparoscopic splenectomy, with or without devascularization around the cardia. Starting two weeks post-surgery, patients began intravenous infusion of PD-1 monoclonal antibody, Tislelizumab, at a dosage of 200mg every three weeks. Three weeks post-surgery, patients commenced oral administration of the targeted therapy, Lenvatinib, with a dosage based on body weight: 8mg (≤60kg) or 12mg (\>60kg), once daily.

Timeline

• Start date: 2024-03-15
• Primary completion: 2027-03-15
• Completion: 2028-03-15
• First posted: 2024-02-28
• Last updated: 2025-08-15

Locations

1 site across 1 country: China