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

Sponsor

Second Affiliated Hospital of Guangzhou Medical University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05608213

Collaborator

(none)

187

Enrollment

Location

Arms

Anticipated Duration (Months)

3.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma Non-resectable	Procedure: Lenvatinib Plus I-125 Seed Brachytherapy Drug: Lenvatinib	Phase 3

Detailed Description

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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

187 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 2, 2022

Anticipated Primary Completion Date :

Oct 31, 2026

Anticipated Study Completion Date :

Dec 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Len-I	Procedure: Lenvatinib Plus I-125 Seed Brachytherapy 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.
Active Comparator: Len	Drug: Lenvatinib Lenvatinib (body weight ≥ 60 kg, 12mg P.O. QD; body weight < 60 kg, 8mg P.O. QD) will be administered to the patients.

Arm

Intervention/Treatment

Experimental: Len-I

Procedure: Lenvatinib Plus I-125 Seed Brachytherapy

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.

Active Comparator: Len

Drug: Lenvatinib

Lenvatinib (body weight ≥ 60 kg, 12mg P.O. QD; body weight < 60 kg, 8mg P.O. QD) will be administered to the patients.

Outcome Measures

Primary Outcome Measures

Overall survival (OS) [4 years]
The time from date of randomization to death due to any cause.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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