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
NCT ID: NCT07187284
Last Updated: 2025-09-22
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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NOT_YET_RECRUITING
PHASE1/PHASE2
62 participants
INTERVENTIONAL
2025-09-30
2027-09-30
Brief Summary
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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.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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.
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.
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.
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.
Interventions
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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.
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.
Eligibility Criteria
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Inclusion Criteria
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
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.
18 Years
75 Years
ALL
No
Sponsors
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Zhongda Hospital
OTHER
Responsible Party
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Gao-jun Teng
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.
Locations
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Zhongda Hospital Affiliated to Southeast University, Department of Interventional and Vascular Surgery
Nanjing, Jiangsu, China
Countries
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Central Contacts
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Facility Contacts
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References
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Shi DD, Guo JA, Hoffman HI, Su J, Mino-Kenudson M, Barth JL, Schenkel JM, Loeffler JS, Shih HA, Hong TS, Wo JY, Aguirre AJ, Jacks T, Zheng L, Wen PY, Wang TC, Hwang WL. Therapeutic avenues for cancer neuroscience: translational frontiers and clinical opportunities. Lancet Oncol. 2022 Feb;23(2):e62-e74. doi: 10.1016/S1470-2045(21)00596-9.
Chang A, Botteri E, Gillis RD, Lofling L, Le CP, Ziegler AI, Chung NC, Rowe MC, Fabb SA, Hartley BJ, Nowell CJ, Kurozumi S, Gandini S, Munzone E, Montagna E, Eikelis N, Phillips SE, Honda C, Masuda K, Katayama A, Oyama T, Cole SW, Lambert GW, Walker AK, Sloan EK. Beta-blockade enhances anthracycline control of metastasis in triple-negative breast cancer. Sci Transl Med. 2023 Apr 26;15(693):eadf1147. doi: 10.1126/scitranslmed.adf1147. Epub 2023 Apr 26.
Mancusi R, Monje M. The neuroscience of cancer. Nature. 2023 Jun;618(7965):467-479. doi: 10.1038/s41586-023-05968-y. Epub 2023 Jun 14.
Silverman DA, Martinez VK, Dougherty PM, Myers JN, Calin GA, Amit M. Cancer-Associated Neurogenesis and Nerve-Cancer Cross-talk. Cancer Res. 2021 Mar 15;81(6):1431-1440. doi: 10.1158/0008-5472.CAN-20-2793. Epub 2020 Dec 17.
Miller BM, Oderberg IM, Goessling W. Hepatic Nervous System in Development, Regeneration, and Disease. Hepatology. 2021 Dec;74(6):3513-3522. doi: 10.1002/hep.32055. Epub 2021 Aug 15.
Fu Y, Shen K, Wang H, Wang S, Wang X, Zhu L, Zheng Y, Zou T, Ci H, Dong Q, Qin LX. Alpha5 nicotine acetylcholine receptor subunit promotes intrahepatic cholangiocarcinoma metastasis. Signal Transduct Target Ther. 2024 Mar 8;9(1):63. doi: 10.1038/s41392-024-01761-z.
Cui Q, Jiang D, Zhang Y, Chen C. The tumor-nerve circuit in breast cancer. Cancer Metastasis Rev. 2023 Jun;42(2):543-574. doi: 10.1007/s10555-023-10095-1. Epub 2023 Mar 31.
Globig AM, Zhao S, Roginsky J, Maltez VI, Guiza J, Avina-Ochoa N, Heeg M, Araujo Hoffmann F, Chaudhary O, Wang J, Senturk G, Chen D, O'Connor C, Pfaff S, Germain RN, Schalper KA, Emu B, Kaech SM. The beta1-adrenergic receptor links sympathetic nerves to T cell exhaustion. Nature. 2023 Oct;622(7982):383-392. doi: 10.1038/s41586-023-06568-6. Epub 2023 Sep 20.
Mohammadpour H, MacDonald CR, McCarthy PL, Abrams SI, Repasky EA. beta2-adrenergic receptor signaling regulates metabolic pathways critical to myeloid-derived suppressor cell function within the TME. Cell Rep. 2021 Oct 26;37(4):109883. doi: 10.1016/j.celrep.2021.109883.
Huang Q, Hu B, Zhang P, Yuan Y, Yue S, Chen X, Liang J, Tang Z, Zhang B. Neuroscience of cancer: unraveling the complex interplay between the nervous system, the tumor and the tumor immune microenvironment. Mol Cancer. 2025 Jan 17;24(1):24. doi: 10.1186/s12943-024-02219-0.
Vermeer PD, Restaino AC, Barr JL, Yaniv D, Amit M. Nerves at Play: The Peripheral Nervous System in Extracranial Malignancies. Cancer Discov. 2025 Jan 13;15(1):52-68. doi: 10.1158/2159-8290.CD-23-0397.
Zahalka AH, Frenette PS. Nerves in cancer. Nat Rev Cancer. 2020 Mar;20(3):143-157. doi: 10.1038/s41568-019-0237-2. Epub 2020 Jan 23.
Zhang Y, Liao Q, Wen X, Fan J, Yuan T, Tong X, Jia R, Chai P, Fan X. Hijacking of the nervous system in cancer: mechanism and therapeutic targets. Mol Cancer. 2025 Feb 6;24(1):44. doi: 10.1186/s12943-025-02246-5.
Winkler F, Venkatesh HS, Amit M, Batchelor T, Demir IE, Deneen B, Gutmann DH, Hervey-Jumper S, Kuner T, Mabbott D, Platten M, Rolls A, Sloan EK, Wang TC, Wick W, Venkataramani V, Monje M. Cancer neuroscience: State of the field, emerging directions. Cell. 2023 Apr 13;186(8):1689-1707. doi: 10.1016/j.cell.2023.02.002.
Other Identifiers
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2025ZDSYLL382-P01
Identifier Type: -
Identifier Source: org_study_id
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