Drug Eluting Beads Transarterial Chemoembolization Versus Conventional Transarterial Chemoembolization for Beyond-Milan-Criteria Hepatocellular Carcinoma After Transjugular Intrahepatic Portosystemic Shunt: A Phase 3, Open Label, Multicenter, Randomized Controlled Trial
This is a Phase 3, open-label, multicenter, randomized controlled clinical trial designed to evaluate the efficacy and safety of Drug-Eluting Bead Transarterial Chemoembolization (DEB-TACE) compared with Conventional Transarterial Chemoembolization (cTACE) in patients with hepatocellular carcinoma (HCC) that is beyond the Milan criteria and who have previously undergone a Transjugular Intrahepatic Portosystemic Shunt (TIPS) procedure. The TIPS procedure is commonly performed to manage complications of portal hypertension, such as variceal bleeding or refractory ascites, in patients with cirrhosis. However, after TIPS, treatment options for HCC-particularly in cases exceeding the Milan criteria-remain limited and not well-defined in current guidelines. While TACE is a standard locoregional therapy for intermediate-stage HCC, its application in patients with a prior TIPS is controversial due to altered hepatic hemodynamics, which may increase the risk of liver toxicity and compromise treatment safety and efficacy. Preliminary retrospective data suggest that DEB-TACE, which uses calibrated drug-eluting microspheres, may offer a safer and more effective alternative to cTACE in this specific patient population by providing more controlled drug delivery and potentially reducing systemic and hepatic toxicity. The primary objective of this study is to determine whether DEB-TACE improves Overall Survival (OS) compared to cTACE in patients with beyond-Milan HCC after TIPS. Secondary objectives include comparing the safety profile, Progression-Free Survival (PFS), Objective Response Rate (ORR), Disease Control Rate (DCR), and Quality of Life (QoL) between the two treatment arms. The study aims to enroll 206 participants who will be randomly assigned in a 1:1 ratio to receive either DEB-TACE or cTACE. The trial will include a 24-month recruitment period and a 24-month treatment and follow-up phase, with a total study duration of 48 months. By directly comparing these two TACE approaches in a prospectively defined and randomized setting, this study seeks to provide high-level evidence to guide the optimal locoregional treatment strategy for HCC patients with a history of TIPS placement.
• histologically or clinically confirmed primary hepatocellular carcinoma, beyond Milan criteria (single lesion \>5 cm OR ≥3 lesions with at least one ≥3 cm). At least one intrahepatic measurable lesion with tumor burden ≤50%, no distant metastasis. No prior antitumor therapy within 12 months before enrollment.
• underwent TIPS procedure for secondary prevention of variceal bleeding or refractory ascites. Confirmed patent TIPS at 1-month follow-up with portosystemic blood flow visible throughout the shunt and Doppler velocity \> 60 cm/s.
• child-Pugh class A or B.
• estimated survival ≥3 months.
• adequate organ function:Neutrophils ≥1.5 × 10⁹/L; Platelets ≥50 × 10⁹/L; Hemoglobin ≥90 g/L; Serum albumin ≥30 g/L; Bilirubin ≤50 μmol/L; AST/ALT ≤5 × upper limit of normal (ULN), ALP ≤4 × ULN; INR ≤2.3; Creatinine ≤1.5 × ULN.