Comparison of SBRT and SIRT With Combination IO for Locally-advanced, Unresectable HCCs (BIIRTH)

Sponsor
Tuen Mun Hospital
Study ID
NCT07293468
Phase
PHASE2/PHASE3
Status
Recruiting
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Conditions

  • Hepatocellular Carcinoma (HCC)

Eligibility Criteria

Sex
ALL
Age
18 Years - 80 Years
Healthy Volunteers
Not accepted

Interventions

  • Transarterial chemoembolization (TACE) — PROCEDURE
    One dose of TACE would be performed as per standardized procedure at 21-35 days preceding SBRT. Celiac and superior mesenteric arterial and porto-venogram would be performed to exclude main portal vein occlusion and to delineate the size(s) and number(s) of tumour nodule(s). Supra-selective cannulation of the supplying tumour artery would follow. The 1:1 lipiodol-cisplatin emulsion prepared by pumping would be slowly injected under fluoroscopic guidance according to the tumour size and arterial blood flow.
  • Stereotactic Body Radiation Therapy (SBRT) — RADIATION
    Patients are immobilized with customized device and abdominal compression or active breathing control. Four-dimensional computed tomography (4D-CT) was phase-sorted into 10 image-sets. A radiation dose of 27.5-50.0 Gy in five fractions, delivered in alternate days, is allowed. The prescription dose is individualized based on normal tissue constraints. This should be based on delivering a maximal tumoricidal dose while respecting the tolerance dose of neighbouring organs-at-risk. SBRT is delivered by dynamic conformal arc therapy, intensity-modulated RT, or volumetric modulated arc RT.
  • SIRT Yttrium-90 — RADIATION
    Patients undergo intrahepatic arterial Y90-radioembolisation (TheraSphere glass microspheres; MDS Nordion, Ottawa, Canada or SIR-Spheres, Sirtex Medical Pty Limited; St. Leonards, NSW, Australia). The administered activity of Y90-glass microspheres was determined by the nuclear medicine physician, medical physicist, radiologist and clinical oncologist using the artery-specific partition model within the limits of radiation safety, taking into account treatment variables including patient's body surface area, tumour-to-normal liver ratio, and liver tumour size. Where possible, personalized dosimetry using the partition model was the default methodology to facilitate selective administration of Y90-radioembolisation avoiding toxicities to the normal liver parenchyma.
  • Atezolizumab & Bevacizumab — DRUG
    Patients will start Atezolizumab-bevacizumab 14days upon completion of SBRT or SIRT. Atezolizumab, if given, is administered via IV infusion at a fixed dose of 1200mg, together with Bevacizumab (start 28days after SBRT/SIRT) via IV infusion at a fixed dose of 15mg/kg, on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator, or after curative surgical intervention is performed with no evidence of residual disease. Patients who transiently or permanently discontinued either atezolizumab or bevacizumab due to an adverse event are allowed to continue with single-agent therapy provided there is ongoing clinical benefit as determined by the investigator.

Study Details

The goal of this clinical trial is to compare the safety and efficacy of sequential Transarterial Chemoembolization (TACE) and Stereotactic body radiation therapy (SBRT) versus Y90-radioembolisation (SIRT), followed by systemic therapy in patients with large, locally advanced, unresectable Hepatocellular carcinoma (HCC). The main question it aims to answer is whether Sequential TACE-SBRT potentially gives longer Progression-free survival (PFS) benefit with similar toxicities as compared with Y90 SIRT. Participants will be recruited via multidisciplinary meetings (MDTs) with hepatobiliary surgeons, medical hepatologists and radiologists with consistent, strict considerations on eligibility and treatment alternatives. Eligible patients will be randomized in 1:1 ratio to received one of the two treatment arms.

Key Dates

Start date
Apr 1, 2024
Status verified
Apr 2026
Primary completion
Mar 31, 2034
Completion
Dec 31, 2034

Study Design

Enrollment
106 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: TACE-SBRT arm
    Combination TACE and SBRT followed by immunotherapy
  • Active Comparator: Y90 SIRT arm
    Combination Y90 SIRT followed by immunotherapy

Primary Outcome Measure

Progression-free survival (PFS) [ Time Frame: defined as the period from the date of starting TACE or Y90-radioembolisation to the time of local, in-field disease progression, or the time of patient death, whichever occurring first; up to 10 years ]

Central Contacts

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