Clinical trial NCT06178198: Radiation Major Hepatectomy to Selectively Treat Large Unifocal Hepatocellular Carcinoma
Official title: An Open-label, Single-arm, Single-center Clinical Trial to Evaluate the Efficacy and Safety of Yttrium-90 Ablative Radioembolization (Radiation Major Hepatectomy) for Unifocal Large Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular Carcinoma
Radioembolization
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2023-12-20
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label, prospective, single-arm, single-center trial
Primary purpose: TREATMENT

Brief summary: The RESCUE trial is a prospective, single-arm clinical study to evaluate the efficacy and safety of ablative radioembolization using Yttrium-90. This treatment is being investigated as a potential curative approach, as well as a bridging or downstaging strategy for surgery, in patients with large hepatocellular carcinoma (greater than 8 cm) who maintain good liver function.

Detailed description: Patients presenting with large hepatocellular carcinoma (greater than 8 cm), whether accompanied by satellite nodules or not, but retaining good liver function, will undergo ablative radioembolization utilizing Yttrium-90 resin microspheres. This approach is designed to deliver an ablative dose to both tumors and the surrounding liver (i.e., margin) with curative intent, while preserving over 30% of the non-tumorous liver volume. The efficacy and safety of this treatment will be evaluated over a period of two years and 90 days, respectively.

Eligibility criteria: Inclusion Criteria:

1. Adults aged 18 and over.
2. Patients diagnosed with hepatocellular carcinoma histologically and/or radiologically (LI-RADS 4 or 5).
3. Patients with no more than five lesions in dynamic contrast-enhanced CT or MRI, and the largest tumor diameter exceeding 8 cm.
4. Patients without vascular invasion and bile duct invasion in dynamic contrast-enhanced CT or MRI.
5. Patients with no extrahepatic metastasis in lung CT and contrast-enhanced abdominal CT or MRI.
6. Patients with no prior treatment for liver cancer.
7. Child-Pugh class A.
8. ECOG performance status of 1 or less.
9. Patients with no major organ dysfunction according to blood tests performed within one month of study enrollment.

   1. Leukocytes ≥ 2,500/µL and ≤ 12,000/µL
   2. Absolute neutrophil count ≥ 1,500 /mm\^3
   3. Hemoglobin ≥ 8.0 g/dL (transfusion allowed to meet this criterion)
   4. Total bilirubin ≤ 3.0 mg/dL
   5. Platelet ≥ 50,000/µL
   6. INR ≤ 2.0 for patients not taking anticoagulants
   7. AST ≤ 200 IU/L (i.e., ≤ 5X upper normal limit)
   8. ALT ≤ 200 IU/L (i.e., ≤ 5X upper normal limit)
   9. ALP ≤ 575 IU/L (i.e., ≤ 5X upper normal limit)
   10. Creatinine ≤ 2.0 mg/dL
10. Patients with a life expectancy of more than 3 months.
11. Patients who have adequately understood the clinical trial and consented in writing.
12. Non-pregnant women of childbearing potential.

Exclusion Criteria:

1. Patients who are not suitable for ablative radioembolization as indicated by pre-treatment testing with macro-aggregated albumin labeled with technetium-99 (99mTc-MAA) for radioembolization.

   1. Cases where the estimated lung dose exceeds 15 Gy when 150 Gy of absorbed dose is administered to the tumor based on the partition method.
   2. Cases with severe hepatic artery-portal vein shunting that might lead to irradiation of the non-tumorous liver segments.
2. Patients whose volume of non-tumorous liver not included in the treatment area is less than 30% of the total non-tumorous liver volume.
3. Patients scheduled to use immunotherapy irrespective of the response to radioembolization.
4. Patients who have had active cancer within the last two years prior to the clinical trial participation.
5. Patients who have undergone surgery or procedures related to the bile duct.
6. Women who are pregnant or breastfeeding.

Primary outcomes:
measure: Objective response rate according to 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: Duration of response according to localized mRECIST
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)
Secondary outcomes:
measure: Objective response rate according to 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: Duration of response according to mRECIST
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: 2-year restricted mean duration of response according to localized mRECIST and mRECIST
timeFrame: Time of response up to progression, subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or 24 months after the initial treatment
measure: Complete response rate according to localized mRECIST and 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: Duration of complete response according to localized mRECIST and 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: 2-year restricted mean DoCR (RMDoCR) according to localized mRECIST and mRECIST
timeFrame: Time of complete response up to progression, subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or 24 months after the initial treatment
measure: Best response within 2-years according to localized mRECIST and 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: Time to best response according to localized mRECIST and 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: Time to progression according to localized mRECIST and 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: Overall survival
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: 2-year restricted mean survival time of overall survival
timeFrame: Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or 24 months the initial treatment
measure: Progression-free survival
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: Hepatic progression-free survival (HPFS)
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: Pathological necrosis rate (%) after curative 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: Time to 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: 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: Rate for conversion to curative resection and 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: Adverse event and serious adverse event
timeFrame: Time of treatment up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first
measure: Changes in Child-Pugh class
timeFrame: Baseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first
measure: Changes in ALBI (albumin-bilirubin) grade
timeFrame: Baseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first
measure: Changes in MELD (model for end-stage liver disease) score
timeFrame: Baseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first
measure: Changes in ECOG (Eastern Cooperative Oncology Group) performance status scale
timeFrame: Baseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first
measure: Changes in health-related quality of life
timeFrame: Baseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first
measure: Changes in regional liver function
timeFrame: Baseline up to 180 days after the initial treatment or subsequent anticancer treatment, whichever comes first
Other outcomes:
measure: Pre-treatment dosimetry based on 99mTc-MAA SPECT-CT
timeFrame: Baseline
measure: Post-treatment dosimetry based on Y90 PET-CT
timeFrame: Within two days after the procedure
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Seoul National University Hospital
name: Jin Woo Choi, MD, PhD
role: STUDY_CHAIR
References:
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