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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Hepatocellular Carcinoma, Portal Vein Tumor Thrombus

Intervention / Treatment
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* Procedure: Stent and Iodine-125 seed strand implantation
* Device: Stent
* Device: Iodine-125 seed
* Drug: Epirubicin
* Drug: Ultra-fluid lipiodol
* Other: Gelatin sponge articles


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Endovascular Brachytherapy&Stent&TACE<br>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. | Procedure: Stent and Iodine-125 seed strand implantation<br>* 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.<br>Device: Stent<br>* Bare stent should be placed through a 7-F, 23-cm-long sheath over the wire.<br>Device: Iodine-125 seed<br>* 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.<br>Drug: Epirubicin<br>* Epirubicin is a chemotherapy drug used in transarterial chemoembolization (TACE).Dosage: Epirubicin 30-60 mg per patient,depending on the situation of the patient.<br>Drug: Ultra-fluid lipiodol<br>* Ultra-fluid lipiodol is a kind of embolization material used in TACE. Standard: 38% ultra-fluid lipiodol .<br>* Other names: lipiodol;Other: Gelatin sponge articles<br>* Gelatin sponge articles embolization material used in TACE. Standard: 350-560 um in diameter.<br>|
| Active Comparator: TACE alone<br>Only TACE is performed. Epirubicin, ultra-fluid lipiodol and gelatin sponge articles are used in TACE. | Drug: Epirubicin<br>* Epirubicin is a chemotherapy drug used in transarterial chemoembolization (TACE).Dosage: Epirubicin 30-60 mg per patient,depending on the situation of the patient.<br>Drug: Ultra-fluid lipiodol<br>* Ultra-fluid lipiodol is a kind of embolization material used in TACE. Standard: 38% ultra-fluid lipiodol .<br>* Other names: lipiodol;Other: Gelatin sponge articles<br>* Gelatin sponge articles embolization material used in TACE. Standard: 350-560 um in diameter.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chemoembolization, Hepatocellular carcinoma, main portal vein tumor thrombus, endovascular brachytherapy, stent