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

Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05984511
• Other study ID #: II2023-162-02
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 1, 2023
• Est. completion date: August 1, 2029

Study information

• Verified date: August 2023
• Source: Third Affiliated Hospital, Sun Yat-Sen University
• Contact: Mingsheng Huang, M.D. & Ph.D.
• Phone: +86-02085253416
• Email: huangmsh[@]mail.sysu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 234
• Est. completion date: August 1, 2029
• Est. primary completion date: August 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Hepatic Portal Vein Tumor Invasion
• Hepatocellular Carcinoma
• Tumor Thrombus

Intervention

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.
• Transcatheter arterial chemoembolization
TACE: cTACE (conventional TACE) or dTACE (drug-eluting beads TACE).

Drug:
• Atezolizumab plus Bevacizumab
Atezolizumab/bevacizumab (1,200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks) .

Locations

Country	Name	City	State
n/a

Sponsors (6)

Lead Sponsor	Collaborator
Third Affiliated Hospital, Sun Yat-Sen University	Fifth Affiliated Hospital, Sun Yat-Sen University, Maoming People's Hospital, Second Affiliated Hospital of Guangzhou Medical University, Shandong Provincial Third Hospital, Sun Yat-sen University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival (OS)	Time from randomization to death from any cause.	2 years
Secondary	Progression free survival (PFS)	Time from randomization to disease progression (mRECIST) or death from any cause, whichever occurred first.	2 years
Secondary	Objective response rate (ORR)	The percentage of patients who had a best overall tumor response rating of CR and PR (mRECIST).	2 years
Secondary	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
Secondary	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