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
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- hPFS
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
- •Creatinine ≤1.5 × ULN AND calculated creatinine clearance ≥30 mL/min.
排除标准
- •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).
- •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.
研究组 & 干预措施
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.
干预措施: EDN combined with TACE/HAIC and Immuno-Targeted Therapy (Combination Product)
Control group
Participants randomized to the control group will receive the current standard of care for the studied patient population, which consists of:
- 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.
- 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.
干预措施: TACE/HAIC plus Immuno-Targeted Therapy (Combination Product)
结局指标
主要结局
hPFS
时间窗: 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
次要结局
- 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)
- SAEs(From date of randomization until the end of study visit at 12 months.)
研究者
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.
Zhongda Hospital