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

NCT07187284 | Not Yet Recruiting Phase 1

• 1 other identifier: 2025ZDSYLL382-P01
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HCC - Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• hPFS

  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 Outcomes (6)

• ORR

  From date of randomization until the first documented objective response (CR or PR), assessed up to 12 months.

• OS

  From date of randomization until date of death from any cause, assessed up to 12 months.

• PFS

  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

  From date of randomization until the first documented objective response (CR or PR) or stable disease (SD), assessed up to 12 months.

• MAE

  From the time of the baseline procedure (ablation surgery) through 30 days post-procedure

Study Arms (2)

Treatment intervention group

EXPERIMENTAL

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

Control group

ACTIVE COMPARATOR

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

Interventions

EDN combined with TACE/HAIC and Immuno-Targeted Therapy COMBINATION_PRODUCT

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.

Treatment intervention group

TACE/HAIC plus Immuno-Targeted Therapy COMBINATION_PRODUCT

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.

Control group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 75 years (inclusive), regardless of gender.
• Diagnosis of CNLC Stage IIIa HCC with portal vein tumor thrombus (vp type 1-3) confirmed by histopathology, cytology, or imaging.
• Progression of disease after first-line systemic therapy.
• At least one measurable lesion according to RECIST 1.1 criteria.
• Child-Pugh class A or B.
• ECOG performance status of 0 to 2.
• Scheduled to undergo TACE or HAIC treatment.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Zhongda Hospital: lead

Study Sites (1)

Zhongda Hospital Affiliated to Southeast University, Department of Interventional and Vascular Surgery

Nanjing, Jiangsu, 210009, China

Location

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MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Central Study Contacts

Tao Pan

CONTACT

+8615850651223; 15850651223@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Teng was elected as an Academician of the Chinese Academy of Sciences in 2021 and as a Fellow of the Chinese Academy of Medical Sciences in 2022.

Study Record Dates

• First Submitted: September 19, 2025
• First Posted: September 22, 2025
• Study Start: September 30, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2027
• Last Updated: September 22, 2025

Record last verified: 2025-09

Locations

CN (1)