Lenvatinib Plus I-125 Seed Brachytherapy vs. Lenvatinib for TACE-refractory HCC

Study Overview
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Brief Summary
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This study is conducted to evaluate the efficacy and safety of lenvatinib plus iodine-125 seed brachytherapy (Len-I) compared with lenvatinib (Len) alone for patients with hepatocellular carcinoma (HCC) refractory to transarterial chemoembolization (TACE).

Detailed Description
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This is a single-center, prospective and randomized controlled trial to evaluate the efficacy and safety of Len-I versus Len alone for patients with TACE-refractory HCC. 187 patients with TACE-refractory HCC will be enrolled in this study. The patients will receive either Len-I or Len alone using an 2:1 randomization scheme. Lenvatinib (body weight ≥ 60 kg, 12mg P.O. QD; body weight < 60 kg, 8mg P.O. QD) will be administered to the patients 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 Len-I arm, iodion-125 seeds will be implanted into the the target lesions (viable intrahepatic tumor and/or vascular tumor thrombus) under CT guidance according to the pre-operative planning within 7 days after lenvatinib administration. Iodion-125 seeds implantation can be repeated on demand during follow-up based on the evaluation of laboratory and imaging examination. The primary end point of this study is overall survival (OS). The secondary endpoints are progression-free survival (PFS), time to progression (TTP), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs).

Official Title
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Lenvatinib Plus Iodine-125 Seed Brachytherapy Compared With Lenvatinib Alone for TACE-refractory Hepatocellular Carcinoma: a Single Center, Prospective, Randomized Control Trail

Conditions
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Hepatocellular Carcinoma Non-resectable

Intervention / Treatment
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* Procedure: Lenvatinib Plus I-125 Seed Brachytherapy
* Drug: Lenvatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HCC confirmed by histopathology and/or cytology, or diagnosed clinically Diagnosis of HCC with TACE refractoriness according to the criteria proposed by Japan Society of Hepatology (2021) Patients who have Tumor recurrence after surgical resection or ablation are allowed to be included At least one measurable intrahepatic target lesion Child-Pugh class A/B Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Life expectancy of at least 3 months Exclusion Criteria: Extrahepatic metastasis Tumor thrombus involving main portal vein or both the first left and right branch of portal vein Vena cava invasion Patients who received prior systemic therapy, immunotherapy, hepatic arterial infusion chemotherapy (HAIC) or radiotherapy for HCC History of organ and cell transplantation History of bleeding from esophagogastric varices History of hepatic encephalopathy Hematologic examination: platelets <50×10^9/L Prothrombin time prolongation ≥ 4s Severe organ (heart, lung, kidney) dysfunction History of malignancy other than HCC

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: Len-I<br> | Procedure: Lenvatinib Plus I-125 Seed Brachytherapy<br>* Lenvatinib (body weight ≥ 60 kg, 12mg P.O. QD; body weight < 60 kg, 8mg P.O. QD) will be administered to the patients. Iodion-125 seeds will be implanted into the the target lesions (viable intrahepatic tumor and/or vascular tumor thrombus) under CT guidance according to the pre-operative planning within 7 days after lenvatinib administration. Iodion-125 seeds implantation can be repeated on demand during follow-up based on the evaluation of laboratory and imaging examination.<br>|
| Active Comparator: Len<br> | Drug: Lenvatinib<br>* Lenvatinib (body weight ≥ 60 kg, 12mg P.O. QD; body weight < 60 kg, 8mg P.O. QD) will be administered to the patients.<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. | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | The time from date of randomization until the first occurrence of disease progression (according to mRECIST) or death due to any cause, whichever occurs first. | 4 years | 
| Time to Progression (TTP) | The time from date of randomization until the first occurrence of disease progression (according to mRECIST). | 4 years | 
| Objective response rate (ORR) | The proportion of patients with the best response of complete response (CR) or partial response (PR) according to mRECIST. | 4 years | 
| Disease control rate (DCR) | The proportion of patients with the best response of CR, PR, or stable disease (SD) according to mRECIST. | 4 years | 
| Adverse Events (AEs) | Number of patients with AEs assessed by Common Terminology Criteria for Adverse Events v5.0. | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular Carcinoma, Lenvatinib, iodion-125 seed