At four major centers in Korea, patients with hepatocellular carcinoma (HCC) that exceed the up-to-7 criteria yet remain locally confined will undergo ablative radioembolization using Yttrium-90 glass microspheres, guided by a standardized dosimetry method. Their treatment response, survival outcomes, and adverse events will be monitored for two years following the procedure.
This prospective, multi-center, open-label, single-arm, phase II clinical trial aims to evaluate the efficacy and safety of ablative radioembolization in patients with hepatocellular carcinoma (HCC) that exceeds the up-to-seven (UT7) criteria but is confined to up to five geographically adjacent Couinaud segments. The primary endpoint is the objective response rate, assessed according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). All patients will receive ablative radioembolization using Yttrium-90 glass microspheres with a personalized dosimetry approach targeting a tumor dose of 700 Gy (±50%). In cases of high tumor burden, a second radioembolization within 180 days of the initial procedure will be permitted at the operators' discretion, provided the cumulative lung dose remains below 50 Gy. Follow-up evaluations, including laboratory tests and dynamic imaging, will be performed at 4 weeks post-treatment and every 3 months thereafter for a total of 2 years. Efficacy data-including tumor response and survival-will be collected, with tumor responses evaluated by both site investigators and a blinded independent central review. Adverse events will be documented and graded according to the Common Terminology Criteria for Adverse Events v5.0. In addition, the incidence of radioembolization-induced liver disease and radiation pneumonitis will be monitored for 6 months following the procedure.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
100
The multicompartment MIRD model (a.k.a. partition model) based on diagnostic CT/MRI and 99mTc-MAA SPECT-CT will be used to plan a targeted dose of 700 Gy (± 50%) to the tumor. Given the high tumor burden, a scheduled second radioembolization within 120 days from the initial treatment will be permitted at the discretion of the operators provided the cumulative lung dose remains below 50 Gy. A scheduled second radioembolization may be considered when the largest tumor diameter exceeds 8 cm, or the estimated lung dose reaches 30 Gy while the tumor absorbed dose remains below the target dose of 700 Gy. The radioactive microsphere delivery device used will be glass-based (TheraSphere; Boston Scientific, MA, USA), in which Y90 is an integral constituent of the biocompatible glass matrix. Dosimetry planning will be made by personalized dosimetry software (Simplicit90y; Boston Scientific).
Gangneung Asan Hospital
Gangneung, Gangwon-do, South Korea
RECRUITINGHallym University Sacred Heart Hospital
Anyang-si, Gyeonggi-do, South Korea
RECRUITINGNational Cancer Center
Ilsan, Gyeonggi-do, South Korea
Objective response rate (ORR) according to the mRECIST
The number of patients with partial or complete response accroding to the mRECIST as the best response, divided by the total number of participants (%)
Time frame: Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
ORR according to the RECIST 1.1
The number of patients with partial or complete response according to the RECIST 1.1 as the best response, divided by the total number of participants (%)
Time frame: Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
ORR according to localized mRECIST and RECIST 1.1
The number of patients with partial or complete response as the best response, divided by the total number of participants (%). In the localized mRECIST and RECIST 1.1, the tumor response is assessed only within radioembolization-treated area.
Time frame: Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Duration of response according to mRECIST, localized mRECIST, and RECIST 1.1
The time from the first documentation of partial or complete response to the first occurrence of progressive disease, death from any cause, or receipt of subsequent anticancer treatment, whichever comes first.
Time frame: Time of response up to progression, subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Overall survival rate
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Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, South Korea
RECRUITINGSeoul National University Hospital
Seoul, South Korea
RECRUITINGSeverance Hospital
Seoul, South Korea
RECRUITINGSeoul Asan Hospital
Seoul, South Korea
NOT_YET_RECRUITINGSamsung Medical Center
Seoul, South Korea
RECRUITINGTime frame: Time of treatment up to participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Progression-free survival rates according to mRECIST, localized mRECIST, and RECIST 1.1
Time frame: Time of treatment up to progression, subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Time-to-progression according to mRECIST, localized mRECIST, and RECIST 1.1
Time frame: Time of treatment up to progression, subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled).
Major pathologic response rate (%) after surgical resection or liver transplantation
The number of patients with major pathologic response of the largest tumor after surgical resection or liver transplantation, divided by the total number of participants who received surgical resection or liver transplanation (%). Major pathologic response refers to ≥ 90% of pathologic necrosis of the largest resected tumor
Time frame: Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Curative conversion rate
Curative conversion: resection, liver transplantation, or percutaneous ablation
Time frame: Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Sustainable complete response rate according to mRECIST more than 1 year
Time frame: Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Locoregional treatment unsuitability rate
LRT unsuitability will be determined if any of the following criteria are met. * Lack of objective response after two sessions of intra-arterial treatments * Development of new HCC within the treatment zone * Development of vascular invasion within the treatment zone * Development of extrahepatic spread
Time frame: Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Time to and reason for subsequent HCC treatment
Time frame: Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Threshold tumor absorbed dose (Gy) to predict radiologic complete response and objective response as the best response by localized mRECIST
Time frame: Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Adverse event and serious adverse event according to CTCAE v5.0
Time frame: Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
The presence or absence of radiation pneumonitis diagnosed by chest simple X-ray or CT
Time frame: Time of treatment up to 180 days after the initial treatment or subsequent anticancer treatment, whichever comes first
The presence or absence of radioembolization-induced liver disease
Time frame: Time of treatment up to 180 days after the initial treatment or subsequent anticancer treatment, whichever comes first