Clinical trial NCT05984511: TACE Plus Atezolizumab/Bevacizumab and I-125 Seeds Brachytherapy for HCC With Branch PVTT
Official title: TACE Plus Atezolizumab/Bevacizumab and I-125 Seeds Brachytherapy for HCC With Branch PVTT: A Phase III, Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Hepatocellular Carcinoma
Hepatic Portal Vein Tumor Invasion
Tumor Thrombus
Keywords: Hepatocellular Carcinoma (HCC)
Portal vein tumor thrombosis (PVTT)
Transcatheter arterial chemoembolization (TACE)
I-125 Seeds Brachytherapy
Atezolizumab plus Bevacizumab
Lead sponsor: Third Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
Collaborators: name: Sun Yat-sen University Cancer Center (SUSUCC)
name: Fifth Affiliated Hospital, Sun Yat-Sen University
name: Second Affiliated Hospital of Guangzhou Medical University
name: Maoming People's Hospital
name: Shandong Province Third hospital
First posted: 2023-08-09
Enrollment: 234
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a multicenter, open-label trial, randomized controlled trial to evaluate the efficacy and safety of TACE-AB-I compared with TACE-AB for the treatment of HCC with branch PVTT.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall survival (OS)
timeFrame: 2 years
Secondary outcomes:
measure: Progression free survival (PFS)
timeFrame: 2 years
measure: Objective response rate (ORR)
timeFrame: 2 years
measure: Duration of portal patency
timeFrame: 2 years
measure: Adverse events (AEs)
timeFrame: 2 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Sun Yat-Sen University
state: Guangzhou
Study officials:
affiliation: Department of Interventional Radiology, The Third Affiliated Hospital of Sun Yat-sen University
name: Mingsheng Huang, M.D. & Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: