EDN Combined With TACE/HAIC and Second-Line Immune-Targeted Treatment Versus TACE/HAIC Alone in Locally Advanced HCC With Portal Vein Tumor Thrombosis After First-Line Therapy Failure: A Prospective, Multicenter, Randomized Controlled Trial

September 19, 2025 updated by: Gao-jun Teng, Zhongda Hospital

Evaluating Endervascular Denervation (EDN) Combined With Transarterial Intervention (TACE/HAIC) and Second-Line Immune-Targeted Therapy in Locally Advanced Hepatocellular Carcinoma (HCC) With Portal Vein Tumor Thrombosis After Progression on First-Line Systemic Therapy: A Prospective, Multicenter, Randomized Controlled Study

The goal of this clinical trial is to evaluate the efficacy and safety of combining endovascular denervation (EDN) with transarterial chemoembolization/ hepatic arterial infusion chemotherapy (TACE/HAIC) plus second-line immune-targeted therapy in patients with locally advanced hepatocellular carcinoma (HCC) who have progressed after first-line systemic therapy and present with portal vein tumor thrombus (PVTT).

The main questions this study aims to answer are:

Does the addition of EDN to standard TACE/HAIC and immune-targeted therapy improve intrahepatic progression-free survival (hPFS) based on RECIST 1.1 criteria? What is the safety profile of the combined treatment, including device-related adverse events? Researchers will compare the experimental group (EDN + TACE/HAIC + immune-targeted therapy) with the control group (TACE/HAIC + immune-targeted therapy alone) in a 1:1 randomized design. A total of 62 participants will be enrolled across 8 centers, with an expected enrollment period of 12 months and a 12-month follow-up period.

Participants will:

Undergo screening assessments including imaging (CT/MRI), blood tests, and ECG within specified time windows.

Receive assigned interventions (EDN procedure or control) during the baseline visit (Day 0).

Attend follow-up visits at 1 month (±7 days), 3 months (±14 days), 6 months (±30 days), 9 months (±30 days), and 12 months (±30 days) for repeated imaging, laboratory tests, and safety evaluations.

Have their tumor response, survival outcomes, and adverse events monitored throughout the study.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

62

Phase

  • Phase 2
  • Phase 1

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

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210009
        • Zhongda Hospital Affiliated to Southeast University, Department of Interventional and Vascular Surgery
        • Contact:

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. Aged 18 to 75 years (inclusive), regardless of gender.
  2. Diagnosis of CNLC Stage IIIa HCC with portal vein tumor thrombus (vp type 1-3) confirmed by histopathology, cytology, or imaging.
  3. Progression of disease after first-line systemic therapy.
  4. At least one measurable lesion according to RECIST 1.1 criteria.
  5. Child-Pugh class A or B.
  6. ECOG performance status of 0 to 2.
  7. Scheduled to undergo TACE or HAIC treatment.
  8. Adequate hematological, hepatic, and renal function within 14 days prior to study initiation, defined as:

White blood cell count ≥2.0×10⁹/L AND neutrophil count ≥1.0×10⁹/L. Platelet count ≥60×10⁹/L. Hemoglobin concentration ≥90 g/L. Total bilirubin ≤2.0 × upper limit of normal (ULN). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 × ULN. Albumin ≥2.8 g/dL. International normalized ratio (INR) ≤1.6. Creatinine ≤1.5 × ULN AND calculated creatinine clearance ≥30 mL/min.

Exclusion Criteria:

  1. Preoperative abdominal CT or MR enhanced scan suggests celiac trunk anatomy is unsuitable for EDN procedure.
  2. History of orthostatic hypotension.
  3. Diffuse liver tumors or extensive extrahepatic metastases with an expected survival of <3 months.
  4. Cachexia or multi-organ failure.
  5. Severe hepatic dysfunction (Child-Pugh class C).
  6. Uncorrectable coagulation dysfunction.
  7. Presence of severe concurrent infection.
  8. Accompanied by Vp4 type portal vein tumor thrombus.
  9. Abnormal blood supply to the target lesion that precludes transarterial interventional therapy.
  10. History of bilioenteric anastomosis within the past year.
  11. Severe allergy to known contrast agents or embolization materials.
  12. Pregnant or lactating women, or individuals with childbearing potential planning pregnancy during the trial period.

  13. Clinically significant (e.g., active) cardiovascular disease, including:

    Unstable angina within ≤6 months prior to randomization. New York Heart Association (NYHA) class ≥II congestive heart failure. Poorly controlled arrhythmia despite medication (patients with controlled atrial fibrillation are eligible), or any clinically significant abnormality found on resting ECG.

    ≥Grade 3 peripheral vascular disease (e.g., symptomatic and interfering with activities of daily living, requiring intervention).

    Transient ischemic attack or subarachnoid hemorrhage within 6 months prior to randomization, or participation in other drug or device clinical trials within 3 months.

  14. History of other malignancies within the past 5 years or concurrent other malignancies.
  15. Any other condition deemed by the investigator as unsuitable for participation in this study.

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: Treatment intervention group
Participants randomized to the treatment intervention group will receive the following combination therapy: 1.A single procedure of Endovascular Denervation (EDN): Percutaneous catheter-based ablation of the peri-arterial sympathetic nerves. 2.On-demand Transarterial Interventional Therapy: This consists of either Transarterial Chemoembolization (TACE) or Hepatic Arterial Infusion Chemotherapy (HAIC), administered based on individual patient's disease assessment and treatment response. 3.Second-line Immuno-Targeted Drug Therapy: Standard systemic therapy with a combination of immune checkpoint inhibitors and targeted agents (e.g., anti-PD-1/PD-L1 antibodies plus tyrosine kinase inhibitors or VEGF inhibitors). The specific drugs are not limited by the protocol and are chosen at the investigator's discretion according to local standards of care.
Combination product: EDN combined with TACE/HAIC and Immuno-Targeted Therapy

Experimental Intervention (Treatment Group):

This arm evaluates a novel combination strategy. Participants will undergo a single session of Endovascular Denervation (EDN) in conjunction with standard care. The complete intervention includes:

Endovascular Denervation (EDN): A one-time, catheter-based percutaneous procedure for the ablation of peri-arterial sympathetic nerves surrounding the common hepatic artery and/or proper hepatic artery. The procedure utilizes a multi-electrode radiofrequency ablation system (e.g., Netrod®). Ablation parameters are set to 60°C for 120 seconds per site, with a minimum of 20 ablations performed to ensure adequate denervation.

On-demand Transarterial Intervention: Following EDN, participants will receive either Transarterial Chemoembolization (TACE) or Hepatic Arterial Infusion Chemotherapy (HAIC), as determined by the treating investigator based on individual patient anatomy and tumor characteristics.
Active Comparator: Control group

Participants randomized to the control group will receive the current standard of care for the studied patient population, which consists of:

  1. On-demand Transarterial Interventional Therapy: This consists of either Transarterial Chemoembolization (TACE) or Hepatic Arterial Infusion Chemotherapy (HAIC), administered based on individual patient's disease assessment and treatment response.
  2. Second-line Immuno-Targeted Drug Therapy: Standard systemic therapy with a combination of immune checkpoint inhibitors and targeted agents (e.g., anti-PD-1/PD-L1 antibodies plus tyrosine kinase inhibitors or VEGF inhibitors). The specific drugs are not limited by the protocol and are chosen at the investigator's discretion according to local standards of care.
Combination product: TACE/HAIC plus Immuno-Targeted Therapy
This is the active comparator intervention representing the current standard-of-care regimen for the study population. Participants randomized to the control group will receive a combination of locoregional and systemic therapy, specifically excluding the experimental Endovascular Denervation (EDN) procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
hPFS
Time Frame: From date of randomization until the date of first documented intrahepatic progression or date of death from any cause, whichever comes first, assessed up to 12 months.
Intrahepatic Progression-Free Survival (hPFS) assessed by RECIST 1.1
From date of randomization until the date of first documented intrahepatic progression or date of death from any cause, whichever comes first, assessed up to 12 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ORR
Time Frame: From date of randomization until the first documented objective response (CR or PR), assessed up to 12 months.
Objective Response Rate (ORR) assessed by RECIST 1.1
From date of randomization until the first documented objective response (CR or PR), assessed up to 12 months.
OS
Time Frame: From date of randomization until date of death from any cause, assessed up to 12 months.
Overall Survival (OS)
From date of randomization until date of death from any cause, assessed up to 12 months.
PFS
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 12 months.
Progression-Free Survival (PFS) assessed by RECIST 1.1
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months.
DCR
Time Frame: From date of randomization until the first documented objective response (CR or PR) or stable disease (SD), assessed up to 12 months.
Disease Control Rate (DCR) assessed by RECIST 1.1
From date of randomization until the first documented objective response (CR or PR) or stable disease (SD), assessed up to 12 months.
MAE
Time Frame: From the time of the baseline procedure (ablation surgery) through 30 days post-procedure
Incidence of Device-Related Composite Major Adverse Events (MAE)
From the time of the baseline procedure (ablation surgery) through 30 days post-procedure
SAEs
Time Frame: From date of randomization until the end of study visit at 12 months.
Incidence of All Adverse Events (AEs) and Serious Adverse Events (SAEs)
From date of randomization until the end of study visit at 12 months.

Collaborators and Investigators

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

Sponsor

Zhongda Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Estimated)

September 30, 2025

Primary Completion (Estimated)

September 30, 2026

Study Completion (Estimated)

September 30, 2027

Study Registration Dates

First Submitted

September 19, 2025

First Submitted That Met QC Criteria

September 19, 2025

First Posted (Actual)

September 22, 2025

Study Record Updates

Last Update Posted (Actual)

September 22, 2025

Last Update Submitted That Met QC Criteria

September 19, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2025ZDSYLL382-P01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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