TACE Plus Atezolizumab/Bevacizumab and I-125 Seeds Brachytherapy for HCC With Branch PVTT

TACE Plus Atezolizumab/Bevacizumab and I-125 Seeds Brachytherapy for HCC With Branch PVTT: A Phase III, Randomized Clinical Trial

The present study aimed to assess the effectiveness of the combination treatment of Atezolizumab/Bevacizumab, transcatheter arterial chemoembolization (TACE) and I-125 Seeds Brachytherapy (TACE-AB-I) in patients with advanced hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT). The investigators confirmed that the combination therapy yielded better survival data than the combined administration of Atezolizumab/Bevacizumab and TACE (TACE-AB) in patients with advanced HCC and Type I/II PVTT (Based on Cheng's PVTT classification).

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma; Hepatic Portal Vein Tumor Invasion; Tumor Thrombus
• Intervention / Treatment: Procedure: I-125 Seeds Brachytherapy in PVTT; Procedure: Transcatheter arterial chemoembolization; Drug: Atezolizumab plus Bevacizumab

Detailed Description

This is a multicenter, open-label trial, randomized controlled to evaluate the efficacy and safety of TACE-AB-I compared with TACE-AB for the treatment of HCC with branch PVTT. 234 HCC patients with branch PVTT will be enrolled in this study. The Patients will be treated with TACE-AB-I or TACE-AB using a 1:1 randomization scheme. TACE will be performed for the patients after randomization. Atezolizumab/bevacizumab (1,200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks) will be started at 3-7 days after the first TACE and I-125 Seeds Brachytherapy 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-AB-I arm, iodion-125 seeds will be implanted into the PVTT (according to the pre-operative planning) under CT guidance within 3-7 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.

• Study Type: Interventional
• Enrollment (Estimated): 234
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mingsheng Huang, M.D. & Ph.D.; Phone Number: +86-02085253416; Email: huangmsh@mail.sysu.edu.cn
• Study Contact Backup: Name: Luwen Mu, M.D.; Phone Number: +86-13660534361; Email: mulw@mail.sysu.edu.cn

Study Locations

• China
  • Guangzhou
    • Guangzhou, Guangzhou, China, 510630
      • Recruiting
      • The Third Affiliated Hospital of Sun Yat-Sen University
      • Contact: Mingsheng Huang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age between18 and 75 years;
• Has a diagnosis of HCC confirmed by radiology, histology, or cytology;
• Type I PVTT or type II PVTT;
• Child-Pugh class A;
• Eastern Cooperative Group performance status (ECOG) score of 0-1;
• No prior systemic therapy for HCC.
• Adequate hematologic and end-organ function;
• At least one measurable intrahepatic target lesion.

Exclusion Criteria:

• Diffuse HCC;
• Cholangiocarcinoma, fibrolamellar, sarcomatoid hepatocellular carcinoma, and mixed hepatocellular/cholangiocarcinoma subtypes (confirmed by histology, or pathology) are not eligible;
• Evidence of extrahepatic spread (EHS);
• Any condition representing a contraindication to TACE or I-125 seeds brachytherapy as determined by the investigators;
• Evidence or history of bleeding diathesis or any hemorrhage or bleeding event >CTCAE grade 3 within 4 weeks prior to randomization;
• Active or history of autoimmune disease or immune deficiency;
• Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding;
• A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment;
• Evidence of bleeding diathesis or significant coagulopathy;
• Pregnant or breastfeeding females;
• Significant cardiovascular disease;
• Severe infection, such as active tuberculosis;
• Serious medical comorbidities;
• History of organ or cells transplantation;
• History of other uncurable malignancies.

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: TACE plus Atezolizumab/Bevacizumab and I-125 Seeds Brachytherapy (TACE-AB-I); TACE will be performed for the patients after randomization. Iodion-125 seeds will be implanted into the PVTT under CT guidance within 3-7 days after the first TACE. Atezolizumab/bevacizumab (1,200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks) will be started at 3-7 days after the first TACE and I-125 Seeds Brachytherapy. TACE and iodion-125 seeds implantation can be repeated on demand during follow-up based on the evaluation of laboratory and imaging examination.	Procedure: I-125 Seeds Brachytherapy in PVTT; Iodine125 seed implantation into the PVTT was conducted 3-7 days after TACE when the results of the liver function tests were comparable to those obtained before TACE. Pre-procedural planning was conducted using a three-dimensional conformal radiation therapy treatment planning system (TPS) to determine the number of Iodine125 seeds required, the target location for implantation, the best percutaneous puncture site and the access route. The targeted zone for implantation was the tumour thrombosis in the segmental portal vein, left/right portal vein. Implantation was guided by CT, and the Iodine125 seeds were implanted into the PVTT using 18 G needles and the implantation gun that housed the Iodine125 seeds in the cartridge chamber.; Other Names: Iodine-125 Seeds Implantation; Procedure: Transcatheter arterial chemoembolization; TACE: cTACE (conventional TACE) or dTACE (drug-eluting beads TACE).; Other Names: TACE; Drug: Atezolizumab plus Bevacizumab; Atezolizumab/bevacizumab (1,200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks) .; Other Names: atezolizumab-bevacizumab; Atez/Bev treatment
Active Comparator: TACE and Atezolizumab/Bevacizumab (TACE-AB); TACE will be performed for the patients after randomization. Atezolizumab/bevacizumab (1,200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks) will be started at 3-7 days after the first TACE. TACE can be repeated on demand during follow-up based on the evaluation of laboratory and imaging examination.	Procedure: Transcatheter arterial chemoembolization; TACE: cTACE (conventional TACE) or dTACE (drug-eluting beads TACE).; Other Names: TACE; Drug: Atezolizumab plus Bevacizumab; Atezolizumab/bevacizumab (1,200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks) .; Other Names: atezolizumab-bevacizumab; Atez/Bev treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Time from randomization to death from any cause.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	Time from randomization to disease progression (mRECIST) or death from any cause, whichever occurred first.	2 years
Objective response rate (ORR)	The percentage of patients who had a best overall tumor response rating of CR and PR (mRECIST).	2 years
Duration of portal patency	The time from randomization until the date that complete portal vein occlusion was confirmed (if the portal vein is patent at diagnosis).	2 years
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

Collaborators and Investigators

• Sponsor: Third Affiliated Hospital, Sun Yat-Sen University
• Collaborators: Fifth Affiliated Hospital, Sun Yat-Sen University; Second Affiliated Hospital of Guangzhou Medical University; Maoming People's Hospital; Shandong Province Third hospital; Sun Yat-sen University Cancer Center (SUSUCC)
• Investigators: Principal Investigator: Mingsheng Huang, M.D. & Ph.D., Department of Interventional Radiology, The Third Affiliated Hospital of Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2023
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: July 26, 2023
• First Submitted That Met QC Criteria: August 8, 2023
• First Posted (Actual): August 9, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 7, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma (HCC); Atezolizumab plus Bevacizumab; Portal vein tumor thrombosis (PVTT); Transcatheter arterial chemoembolization (TACE); I-125 Seeds Brachytherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab; Atezolizumab; Antibodies, Monoclonal
• Other Study ID Numbers: II2023-162-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Plan to share IPD with collaborators.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No