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

Southeast University

Status and phase: Not yet enrolling; Phase 2; Phase 1

Conditions: HCC - Hepatocellular Carcinoma

Treatments: Combination Product: EDN combined with TACE/HAIC and Immuno-Targeted Therapy; Combination Product: TACE/HAIC plus Immuno-Targeted Therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT07187284

2025ZDSYLL382-P01

Details and patient eligibility

About

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.

Enrollment: 62 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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62 participants in 2 patient groups

Treatment intervention group

Experimental group

Description:

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.

Treatment:

Combination Product: EDN combined with TACE/HAIC and Immuno-Targeted Therapy

Control group

Active Comparator group

Description:

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.

Treatment:

Combination Product: TACE/HAIC plus Immuno-Targeted Therapy