DEB-TACE vs cTACE in HCC After TIPS (UPGRADE)

April 27, 2026 updated by: Wenzhe Fan, First Affiliated Hospital, Sun Yat-Sen University

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

206

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 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.
  2. 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.
  3. child-Pugh class A or B.
  4. estimated survival ≥3 months.
  5. 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.

Exclusion Criteria:

  1. diffuse hepatic infiltration, unassessable lesions on imaging, or tumor burden >50%.
  2. simultaneous portal vein branch tumor thrombus or main portal vein tumor thrombus.
  3. underwent liver transplantation or antitumor therapy after TIPS placement.
  4. contraindications to TACE (e.g., portosystemic shunt, hepatofugal blood flow, significant atherosclerosis).
  5. presence of brain metastases.
  6. Allergy to contrast agents.
  7. pregnancy, breastfeeding, or planning pregnancy within 2 years.
  8. co-infection with HIV or syphilis.
  9. concurrent other malignancy or history of other malignancy within the past 5 years.
  10. severe cardiac, renal, or other organ dysfunction.
  11. active clinically severe infection > Grade 2 (per NCI-CTC v5.0).
  12. psychiatric/psychological conditions that may impair informed consent.
  13. participation in other drug clinical trials within 12 months prior to enrollment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: DEB-TACE group
Procedure: DEB-TACE
Experienced interventional radiologists perform transarterial chemoembolization using drug-eluting microspheres (100-300 μm or 300-500 μm) loaded with chemotherapeutic agents (e.g., 70 mg epirubicin or doxorubicin). The procedure involves superselective catheterization of tumor-feeding arteries, with embolization endpoint being angiographic stasis of arterial flow. Repeat treatments are based on 6-8 week imaging, if residual active lesions and preserved liver function are present. Treatment is discontinued upon disease progression, non-operable conditions, or persistent liver impairment.
Experimental: cTACE group
Procedure: cTACE
Patients receive conventional transarterial chemoembolization using ethiodized oil loaded with chemotherapeutic agents (e.g., 40 mg epirubicin or doxorubicin) followed by gelatin sponge particle embolization if needed. Procedures are performed by experienced interventional radiologists with superselective catheterization. Repeat treatments are based on 6-8 week imaging, provided liver function is preserved. Treatment stops upon disease progression, vascular inoperability, or sustained liver impairment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 24 months
Time interval from date of randomization until the date of death from any cause, whichever came first, assessed up to 24 months
From date of randomization until the date of death from any cause, whichever came first, assessed up to 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Time interval from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Tumor response
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Defined as the proportion of patients achieving complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) according to mRECIST criteria.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Adverse event
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Defined as the occurrence of ≥ Grade 3 hematological or non-hematological toxicities, graded per CTCAE v5.0 criteria.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

First Affiliated Hospital, Sun Yat-Sen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2025

Primary Completion (Estimated)

December 31, 2029

Study Completion (Estimated)

December 31, 2029

Study Registration Dates

First Submitted

December 4, 2025

First Submitted That Met QC Criteria

December 23, 2025

First Posted (Actual)

January 7, 2026

Study Record Updates

Last Update Posted (Actual)

May 1, 2026

Last Update Submitted That Met QC Criteria

April 27, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • [2025]634

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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