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

Not Applicable
Recruiting
Conditions
Hepatic Portal Vein Tumor Invasion
Hepatocellular Carcinoma
Tumor Thrombus
Interventions
Procedure: I-125 Seeds Brachytherapy in PVTT
Procedure: Transcatheter arterial chemoembolization
Registration Number
NCT05984511
Lead Sponsor
Third Affiliated Hospital, Sun Yat-Sen University
Brief Summary

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).

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
234
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
TACE plus Atezolizumab/Bevacizumab and I-125 Seeds Brachytherapy (TACE-AB-I)Atezolizumab plus BevacizumabTACE 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.
TACE and Atezolizumab/Bevacizumab (TACE-AB)Atezolizumab plus BevacizumabTACE 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.
TACE plus Atezolizumab/Bevacizumab and I-125 Seeds Brachytherapy (TACE-AB-I)I-125 Seeds Brachytherapy in PVTTTACE 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.
TACE plus Atezolizumab/Bevacizumab and I-125 Seeds Brachytherapy (TACE-AB-I)Transcatheter arterial chemoembolizationTACE 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.
TACE and Atezolizumab/Bevacizumab (TACE-AB)Transcatheter arterial chemoembolizationTACE 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.
Primary Outcome Measures
NameTimeMethod
Overall survival (OS)2 years

Time from randomization to death from any cause.

Secondary Outcome Measures
NameTimeMethod
Progression free survival (PFS)2 years

Time from randomization to disease progression (mRECIST) or death from any cause, whichever occurred first.

Objective response rate (ORR)2 years

The percentage of patients who had a best overall tumor response rating of CR and PR (mRECIST).

Duration of portal patency2 years

The time from randomization until the date that complete portal vein occlusion was confirmed (if the portal vein is patent at diagnosis).

Adverse events (AEs)2 years

Number of patients with AE, treatment-related AE (TRAE), AE of special interest (AESI), serious adverse event (SAE), assessed by NCI CTCAE v5.0.

Trial Locations

Locations (1)

The Third Affiliated Hospital of Sun Yat-Sen University

🇨🇳

Guangzhou, Guangzhou, China

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