Clinical trial NCT06773845: Building Evidence for Ablative Internal Radiation Therapy in Localized HCC Beyond the Up-To-7 Criteria
Official title: Building Evidence for Ablative Internal Radiation Therapy Using Yttrium-90 Glass Microspheres in Localized Hepatocellular Carcinoma Beyond the Up-To-7 Criteria
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hepatocellular Carcinoma (HCC)
Radioembolization
Keywords: Hepatocellular carcinoma
Radioembolization
SIRT
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: Boston Scientific Corporation
First posted: 2025-01-14
Enrollment: 100
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion criteria

* Adult aged 19 and over
* HCC diagnosed by histology or non-invasive criteria of the American Association for the Study of Liver Disease
* Unresectable HCC beyond the UT7 criteria: the sum of the diameter of the largest tumor (cm) and the number of tumors \> 7
* Localized HCC: all tumors are in the one to five geographically adjacent Couinaud segments
* No current or previous HCC in the untreated liver (i.e., future liver remnant \[FLR\])
* FLR volume \> 30% of total non-tumorous liver volume
* Child-Pugh class A
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
* No major organ dysfunction according to blood test performed within two months of study enrollment:

  * Leukocytes ≥ 2,000/µL and ≤ 15,000/µL
  * Hemoglobin ≥ 8.0 g/dL (transfusion allowed to meet this criterion)
  * Total bilirubin ≤ 2.0 mg/dL
  * Platelet ≥ 40,000/µL
  * International normalized ratio (INR) ≤ 2.0 for patients not taking anticoagulants
  * Aspartate transaminase (AST) ≤ 200 IU/L (i.e., ≤ 5X upper normal limit)
  * Alanine transaminase (ALT) ≤ 200 IU/L (i.e., ≤ 5X upper normal limit)
  * Creatinine ≤ 2.5 mg/dL
* Patients with a life expectancy of more than 3 months
* For women of childbearing age, a negative serum pregnancy test
* Patients who have adequately understood the clinical trial and consented in writing

Exclusion Criteria:

* HCC with vascular invasion and/or bile duct invasion on dynamic computed tomography (CT) or magnetic resonance imaging (MRI)
* HCC with extrahepatic spread on chest CT and abdominal CT or MRI
* Multinodular disseminated HCC: largest tumor size \< 6 cm, or number of tumors \> 10
* Patients who are not suitable for ablative radioembolization as indicated by pre-treatment mapping with 99mTc-macroaggregated albumin (MAA):

  * Cases where the estimated lung dose exceeds 30 Gy when 350 Gy of tumor absorbed dose is administered to the tumor based on the multicompartment Medical Internal Radiation Dose (MIRD) model
  * Cases with severe hepatic artery-portal vein shunting that might lead to irradiation of the non-tumorous liver segments
  * Cases where the operator determines that there is substantial adhesion with the surrounding organs such as the bowel, making ablative radioembolization infeasible
* Cases where the operator judges that the occurrence of even mild radiation pneumonitis could be fatal, based on marked emphysema or interstitial lung disease findings on chest CT
* Patients who have had active cancer within the last two years prior to the study enrollment
* History of severe allergy of intolerance to contrast agents
* Contraindication to angiography or selective visceral catheterization

Primary outcomes:
measure: Objective response rate (ORR) according to the mRECIST
timeFrame: 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)
Secondary outcomes:
measure: ORR according to the RECIST 1.1
timeFrame: 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)
measure: ORR according to localized mRECIST and RECIST 1.1
timeFrame: 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)
measure: Duration of response according to mRECIST, localized mRECIST, and RECIST 1.1
timeFrame: 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)
measure: Overall survival rate
timeFrame: 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)
measure: Progression-free survival rates according to mRECIST, localized mRECIST, and RECIST 1.1
timeFrame: 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)
measure: Time-to-progression according to mRECIST, localized mRECIST, and RECIST 1.1
timeFrame: 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).
measure: Major pathologic response rate (%) after surgical resection or liver transplantation
timeFrame: 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)
measure: Curative conversion rate
timeFrame: 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)
measure: Sustainable complete response rate according to mRECIST more than 1 year
timeFrame: 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)
measure: Locoregional treatment unsuitability rate
timeFrame: 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)
measure: Time to and reason for subsequent HCC treatment
timeFrame: 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)
measure: Threshold tumor absorbed dose (Gy) to predict radiologic complete response and objective response as the best response by localized mRECIST
timeFrame: 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)
measure: Adverse event and serious adverse event according to CTCAE v5.0
timeFrame: 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)
measure: The presence or absence of radiation pneumonitis diagnosed by chest simple X-ray or CT
timeFrame: Time of treatment up to 180 days after the initial treatment or subsequent anticancer treatment, whichever comes first
measure: The presence or absence of radioembolization-induced liver disease
timeFrame: Time of treatment up to 180 days after the initial treatment or subsequent anticancer treatment, whichever comes first
Other outcomes:
Locations:
city: Ilsan
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Seoul National University Hospital
name: Jin Woo Choi, MD, PhD
role: STUDY_CHAIR
References: