AzTrials
AzTrials

HCC - Hepatocellular CarcinomaPhase 1/2NCT07187284

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

A Phase 1/2 study testing EDN combined with TACE/HAIC and Immuno-Targeted Therapy and TACE/HAIC plus Immuno-Targeted Therapy in people with HCC - Hepatocellular Carcinoma, run by Zhongda Hospital at 1 site in China.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
HCC - Hepatocellular Carcinoma
What is being tested?
EDN combined with TACE/HAIC and Immuno-Targeted Therapy and TACE/HAIC plus Immuno-Targeted Therapy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
1 siteChina
Study dates
30 Sep 2025to 30 Sep 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 9Show fewer
  • 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.

Who cannot join

  • 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.
Show all 18Show fewer
  • 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).
  • Transient ischemic attack or subarachnoid hemorrhage within 6 months prior to randomization, or participation in other drug or device clinical trials within 3 months.
  • History of other malignancies within the past 5 years or concurrent other malignancies.
  • Any other condition deemed by the investigator as unsuitable for participation in this study.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Tao Pan contact

+8615850651223

15850651223@126.com

China1 site

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

    Nanjing, Jiangsu, 210009

    Pan, +8615850651223, 15850651223@126.com

Other trials in China

About this study

Official title: 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:

Read more

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.

Being tested
EDN combined with TACE/HAIC and Immuno-Targeted Therapy, TACE/HAIC plus Immuno-Targeted Therapy
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EDN combined with TACE/HAIC and Immuno-Targeted TherapyCombination 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.

  • TACE/HAIC plus Immuno-Targeted TherapyCombination 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.

Study groups in NCT07187284
Study groupRoleWhat they receive
Treatment intervention groupExperimentalParticipants 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.
Receives: Combination Product: EDN combined with TACE/HAIC and Immuno-Targeted Therapy
Control groupActive comparatorParticipants 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.
Receives: Combination Product: TACE/HAIC plus Immuno-Targeted Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. hPFS

    Intrahepatic Progression-Free Survival (hPFS) assessed by RECIST 1.1

    Measured: 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)

  1. ORR

    Objective Response Rate (ORR) assessed by RECIST 1.1

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

  2. OS

    Overall Survival (OS)

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

  3. PFS

    Progression-Free Survival (PFS) assessed by RECIST 1.1

    Measured: 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.

  4. DCR

    Disease Control Rate (DCR) assessed by RECIST 1.1

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

  5. MAE

    Incidence of Device-Related Composite Major Adverse Events (MAE)

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

  6. SAEs

    Incidence of All Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Measured: From date of randomization until the end of study visit at 12 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Sep 2025
  2. Study start30 Sep 2025 (estimated)
  3. Primary completion30 Sep 2026 (estimated)
  4. Study completion30 Sep 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
62 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07187284
Sponsor's protocol ID
2025ZDSYLL382-P01
Status last verified
Sep 2025
First submitted
19 Sep 2025
Last updated
22 Sep 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 35114133

  • 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.

    PubMed 37099632

  • 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.

    PubMed 37316719

  • 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.

    PubMed 33334813

  • 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.

    PubMed 34256416

  • 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.

    PubMed 38453934

  • 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.

    PubMed 36997828

  • 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.

    PubMed 37731001

  • 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.

    PubMed 34706232

  • 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.

    PubMed 39825376

  • 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.

    PubMed 39801235

  • 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.

    PubMed 31974491

  • 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.

    PubMed 39915765

  • 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.

    PubMed 37059069

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing EDN combined with TACE/HAIC and Immuno-Targeted Therapy and TACE/HAIC plus Immuno-Targeted Therapy in people with HCC - Hepatocellular Carcinoma, run by Zhongda Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 22 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Tao Pan (+8615850651223, 15850651223@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07187284, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in