TACE Plus Multikinase Inhibitor and I-125 Seeds Brachytherapy for HCC With Branch PVTT

Study Overview
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Brief Summary
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This study is conducted to evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib and iodion-125 seeds brachytherapy (TACE-Len-I) compared with TACE combined with lenvatinib (TACE-Len) for hepatocellular carcinoma (HCC) with portal vein branch tumor thrombus (branch PVTT).

Detailed Description
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This is an single center, randomized controlled trial to evaluate the efficacy and safety of TACE-Len-I compared with TACE-Len for the treatment of HCC with branch PVTT. 171 HCC patients with branch PVTT will be enrolled in this study. The Patients will be treated with TACE-Len-I or TACE-Len using an 2:1 randomization scheme. TACE will be performed for the patients after randomization. Lenvatinib (body weight ≥ 60 kg, 12mg P.O. QD; body weight < 60 kg, 8mg P.O. QD) will be started at 3-7 days after the first TACE and last until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first. For patients in the TACE-Len-I arm, iodion-125 seeds will be implanted into the PVTT (according to the pre-operative planning) under CT guidance within 14 days after the first TACE. TACE and iodion-125 seeds implantation can be repeated on demand during follow-up based on the evaluation of laboratory and imaging examination.

Official Title
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Transarterial Chemoembolization Combined With Lenvatinib and Iodion-125 Seeds Brachytherapy for Hepatocellular Carcinoma With Portal Vein Branch Tumor Thrombus: a Single Center, Prospective, Randomized Control Trail

Conditions
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Hepatocellular Carcinoma Non-resectable

Intervention / Treatment
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* Procedure: TACE combined with lenvatinib and iodion-125 seeds brachytherapy
* Procedure: TACE combined with lenvatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between18 and 75 years. HCC confirmed by histopathology and/or cytology, or diagnosed clinically. Accompanied with tumor thrombus involving unilateral portal vein branch. Child-Pugh class A or B. Eastern Cooperative Group performance status (ECOG) score of 0-2. Serum bilirubin ≤ 51.3 μmol/L, albumin ≥ 28g/L, ALT and AST ≤ 5 times of the upper normal limit, and creatinine ≤ 20g/L. Prothrombin time prolonged for less than 4s or international normalized ratio < 1.7. Neutrophilic granulocyte count ≥ 1.5×10^9/L, platelet count ≥ 50×10^9/L, and hemoglobin level ≥ 85g/L; At least one measurable intrahepatic target lesion. Life expectancy of at least 3 months. Exclusion Criteria: Diffuse HCC. Extrahepatic metastasis. Tumor thrombus involving both the left and right branch of portal vein or main portal vein. Hepatic vein and/or vena cava invasion. History of organ or cells transplantation. Previous treatment with TACE, intra-arterial infusion chemotherapy, radiotherapy or systemic therapy. History of other malignancies. Serious medical comorbidities. Female patients who are pregnancy or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: TACE-Len-I<br>TACE combined with lenvatinib and iodion-125 seeds brachytherapy | Procedure: TACE combined with lenvatinib and iodion-125 seeds brachytherapy<br>* TACE will be performed for the patients after randomization. Lenvatinib (body weight ≥ 60 kg, 12mg P.O. QD; body weight < 60 kg, 8mg P.O. QD) will be started at 3-7 days after the first TACE and last until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first. Iodion-125 seeds will be implanted into the PVTT under CT guidance within 14 days after the first TACE. TACE and iodion-125 seeds implantation can be repeated on demand during follow-up based on the evaluation of laboratory and imaging examination.<br>|
| Active Comparator: TACE-Len<br>TACE combined with lenvatinib | Procedure: TACE combined with lenvatinib<br>* TACE will be performed for the patients after randomization and it can be repeated on demand during follow-up based on the evaluation of laboratory and imaging examination. Lenvatinib (body weight ≥ 60 kg, 12mg P.O. QD; body weight < 60 kg, 8mg P.O. QD) will be started at 3-7 days after the first TACE and last until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | The time from date of randomization to death due to any cause. | 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events (AEs) | Number of patients with AE, treatment-related AE (TRAE), AE of special interest (AESI), serious adverse event (SAE), assessed by NCI CTCAE v5.0. | 2 years. | 
| Progression free survival (PFS) assessed by investigators according to Modified Response Evalutaion Criteria in Solid Tumors (mRECIST) | The time from date of randomization until the first occurrence of disease progression (PD) or death due to any cause, whichever occurs first. | 2 years. | 
| Objective response rate (ORR) assessed by investigators according to mRECIST | The percentage of patients who had a best overall tumor response rating of complete response (CR) or partial response (PR). | 2 years. | 
| Disease control rate (DCR) assessed by investigators according to mRECIST | The percentage of patients who had a tumor response rating of CR, PR, or stable disease (SD). | 2 years. | 
| Duration of portal patency | The time from randomization until the date that complete portal vein occlusion was confirmed. | 2 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular Carcinoma, Transarterial chemoembolization, Tyrosine kinase inhibitor, iodion-125 seed