Endovascular Brachytherapy Combined With Stent Placement and TACE for HCC With Main Portal Vein Tumor Thrombus

Endovascular Brachytherapy Combined With Stent Placement and Transcatheter Arterial Chemoembolization (TACE) for Treatment of HCC With Main Portal Vein Tumor Thrombus Versus TACE Alone: a Prospective Randomized Controlled Multicentre Trial

It is a prospective and multi-center clinical research in China to compare the efficacy, safety and related impact factors between TACE alone and endovascular brachytherapy combined with stent placement and TACE for HCC with main portal vein tumor thrombus.

Study Overview

• Status: Unknown
• Conditions: Hepatocellular Carcinoma; Portal Vein Tumor Thrombus
• Intervention / Treatment: Drug: Ultra-fluid lipiodol; Other: Gelatin sponge articles; Procedure: Stent and Iodine-125 seed strand implantation; Device: Stent; Device: Iodine-125 seed; Drug: Epirubicin

Detailed Description

It is an open random prospective phase III clinical trial conducted by Principal Investigator Professor Zhi-ping Yan.Investigators in twenty-seven hospitals in China participate in.Patients with unresectable HCC with main portal vein tumor thrombus are enrolled. The investigators propose to recruitment 253 patients who are randomly assigned into the combined group (treated with endovascular brachytherapy combined with stent placement and TACE) and the control group (treated with TACE alone).There are 127 patients in combined group and 126 patients in control group. The criteria of inclusion and exclusion, and the methods of lab tests, imaging modality and treatment procedures are the same.

• Study Type: Interventional
• Enrollment (Anticipated): 253
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Zihan Zhang, MD; Phone Number: +8615901785843; Email: zhangzihan0217@126.com
• Study Contact Backup: Name: Wen Zhang, MD; Phone Number: +8613774267409; Email: wenzhangxiao@126.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Department of Interventional Radiology, Zhongshan Hospital, Fudan University
      • Contact: Jianjun Luo, MD; Email: zhangzihan0217@126.com
      • Principal Investigator: Zhinping Yan, MD
      • Sub-Investigator: Jianjun Luo, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• (1) Hepatocellular carcinoma(HCC) diagnosis confirmed by needle biopsy or by two coincidental imaging techniques associated with increased α-fetoprotein according to the American Association for the Study of Liver Diseases (AASLD) guidelines;
• (2) According to the Barcelona Clinic Liver Cancer staging classification, HCC was unsuitable for resection, liver transplantation or percutaneous radiofrequency ablation;
• (3) Tumor thrombus, a low-attenuation intraluminal filling defect extending from intrahepatic portal vein branches adjacent to primary tumor into main portal vein, was confirmed by contrast-enhanced abdominal computer tomography (CT) or magnetic resonance imaging (MRI)
• (4) At least the first-order branch of the intrahepatic portal vein was patent in one lobe;
• (5) Child-Pugh classification grade A or B;
• (6) Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less;

Exclusion Criteria:

• (1) Patients had a history of any therapy for HCC or portal vein tumor thrombus;
• (2) Advanced liver disease (bilirubin levels >3 mg/dL, Aspartate transaminase or Alanine aminotransferase >5 × upper limit of normal)；
• (3) Tumor invade the Inferior Vena Cava, extrahepatic spread;
• (4) Any contraindication to an arterial procedure such as impaired clotting tests (platelet count below 50 × 109/L or prothrombin activity below 50 %);
• (5) Renal failure,cardiac ejection fraction (<50 %) or end-stage disease;
• (6) Patients who were not capable of cooperation during the procedure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Endovascular Brachytherapy&Stent&TACE; Transarterial chemoembolization (TACE) is performed immediately following Iodine-125 seed strand and stent implantation. Epirubicin,ultra-fluid lipiodol and gelatin sponge articles are used in TACE.	Drug: Ultra-fluid lipiodol; Ultra-fluid lipiodol is a kind of embolization material used in TACE. Standard: 38% ultra-fluid lipiodol .; Other Names: lipiodol; Other: Gelatin sponge articles; Gelatin sponge articles embolization material used in TACE. Standard: 350-560 um in diameter.; Procedure: Stent and Iodine-125 seed strand implantation; The patent second-order branch of the intrahepatic portal vein was punctured with a 22-gauge Chiba needle under ultrasound guidance.Stent and Iodine-125 seed strand are implanted by two 0.035-inch,150-cm-long wire.; Device: Stent; Bare stent should be placed through a 7-F, 23-cm-long sheath over the wire.; Device: Iodine-125 seed; The number of Iodine-125 seeds planned to be implanted was calculated by the following formula: N = length of obstructed main portal vein (mm)/4.5 + 4. These seeds were arranged linearly and sealed into a 4-F catheter continuously to construct a Iodine-125 seed strand.; Drug: Epirubicin; Epirubicin is a chemotherapy drug used in transarterial chemoembolization (TACE).Dosage: Epirubicin 30-60 mg per patient,depending on the situation of the patient.
Active Comparator: TACE alone; Only TACE is performed. Epirubicin, ultra-fluid lipiodol and gelatin sponge articles are used in TACE.	Drug: Ultra-fluid lipiodol; Ultra-fluid lipiodol is a kind of embolization material used in TACE. Standard: 38% ultra-fluid lipiodol .; Other Names: lipiodol; Other: Gelatin sponge articles; Gelatin sponge articles embolization material used in TACE. Standard: 350-560 um in diameter.; Drug: Epirubicin; Epirubicin is a chemotherapy drug used in transarterial chemoembolization (TACE).Dosage: Epirubicin 30-60 mg per patient,depending on the situation of the patient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall Survival	From the date of randomization until the date of death from any cause, assessed up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time To Progression	Time to progression follow-up is done at three months interval after lesions defined as stable with treatment of TACE or combined therapy six months after enrollment until lesions are defined as disease progression.	From the date of first procedure of TACE or combined therapy until the time when the disease progresses from an intermediate to an advanced stage as defined by specific events, assessed up to 24 months

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Collaborators: The First Affiliated Hospital with Nanjing Medical University; Changhai Hospital; The First Affiliated Hospital of Anhui Medical University; Zhongshan Hospital Xiamen University; LanZhou University; Cancer Institute and Hospital, Chinese Academy of Medical Sciences; RenJi Hospital; Hunan Cancer Hospital; Second Affiliated Hospital, School of Medicine, Zhejiang University; Ruijin Hospital; First Affiliated Hospital of Zhejiang University; The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Zhengzhou University; Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University; Wuhan Union Hospital, China; Fujian Medical University Union Hospital; Zhejiang University; First Hospital of China Medical University; The First Affiliated Hospital of Shanxi Medical University; Harbin Medical University; Fujian Provincial Hospital; Tengzhou Central People's Hospital; ZhuHai Hospital; Lishui Country People's Hospital; The Second People's Hospital of Yibin; Yancheng Third People's Hospital; Changzhou Wujin People's Hospital
• Investigators: Study Director: Jianjun Luo, MD, Department of Interventional Radiology, Zhongshan Hospital, Fudan University; Principal Investigator: Zhiping Yan, MD, Department of Interventional Radiology, Zhongshan Hospital, Fudan University

Publications and helpful links

General Publications

• Luo J, Yan Z, Liu Q, Qu X, Wang J. Endovascular placement of iodine-125 seed strand and stent combined with chemoembolization for treatment of hepatocellular carcinoma with tumor thrombus in main portal vein. J Vasc Interv Radiol. 2011 Apr;22(4):479-89. doi: 10.1016/j.jvir.2010.11.029.
• Luo JJ, Zhang ZH, Liu QX, Zhang W, Wang JH, Yan ZP. Endovascular brachytherapy combined with stent placement and TACE for treatment of HCC with main portal vein tumor thrombus. Hepatol Int. 2016 Jan;10(1):185-95. doi: 10.1007/s12072-015-9663-8. Epub 2015 Sep 4.
• Yang M, Fang Z, Yan Z, Luo J, Liu L, Zhang W, Wu L, Ma J, Yang Q, Liu Q. Transarterial chemoembolisation (TACE) combined with endovascular implantation of an iodine-125 seed strand for the treatment of hepatocellular carcinoma with portal vein tumour thrombosis versus TACE alone: a two-arm, randomised clinical trial. J Cancer Res Clin Oncol. 2014 Feb;140(2):211-9. doi: 10.1007/s00432-013-1568-0. Epub 2013 Dec 28. Erratum In: J Cancer Res Clin Oncol. 2014 Apr;140(4):687-8.

Study record dates

Study Major Dates

• Study Start: January 1, 2017
• Primary Completion (Anticipated): October 1, 2020
• Study Completion (Anticipated): November 1, 2020

Study Registration Dates

• First Submitted: November 20, 2016
• First Submitted That Met QC Criteria: November 20, 2016
• First Posted (Estimate): November 22, 2016

Study Record Updates

• Last Update Posted (Actual): June 11, 2020
• Last Update Submitted That Met QC Criteria: June 9, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: stent; chemoembolization; Hepatocellular carcinoma; main portal vein tumor thrombus; endovascular brachytherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Embolism and Thrombosis; Liver Neoplasms; Carcinoma, Hepatocellular; Thrombosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents, Local; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Trace Elements; Micronutrients; Antibiotics, Antineoplastic; Epirubicin; Iodine; Cadexomer iodine; Ethiodized Oil
• Other Study ID Numbers: ZS-IR-2016