Radiation Major Hepatectomy to Selectively Treat Large Unifocal Hepatocellular Carcinoma

Phase 2

Recruiting

• Conditions: Hepatocellular Carcinoma
• Interventions: Procedure: Ablative radioembolization using Yttrium-90 resin microspheres

• Registration Number: NCT06178198
• Lead Sponsor: Seoul National University Hospital

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.

Study Timeline

• Study Start: 2023-11-08
• Study First Submitted: 2023-11-30
• Study First Submitted QC: 2023-12-11
• Study First Posted: 2023-12-20
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-05
• Last Update Posted: 2025-01-07
• Primary Completion: 2026-11-30
• Study Completion: 2026-11-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ablative radioembolization for large HCC	Ablative radioembolization using Yttrium-90 resin microspheres	Yttrium-90 resin microspheres (SIR-Sphere, SIRTEX) will be administered to cover the main tumor, satellite nodules, and margin.

Primary Outcome Measures

Name	Time	Method
Objective response rate according to localized mRECIST	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 number of patients with partial or complete response as the best local response divided by the total number of participants
Duration of response according to localized mRECIST	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)	The time from first documentation of partial or complete response to the first documentation of progressive disease, death due to any cause, or receipt of subsequent anticancer treatment, whichever comes first

Secondary Outcome Measures

Name	Time	Method
Duration of complete response according to localized mRECIST and mRECIST	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)
2-year restricted mean DoCR (RMDoCR) according to localized mRECIST and mRECIST	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
Objective response rate according to mRECIST.	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	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)
2-year restricted mean duration of response according to localized mRECIST and mRECIST	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
Complete response rate according to localized mRECIST and mRECIST	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)
Overall survival	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 subsequent HCC treatment	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)
Hepatic progression-free survival (HPFS)	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)
Pathological necrosis rate (%) after curative resection or liver transplantation	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)
Changes in ECOG (Eastern Cooperative Oncology Group) performance status scale	Baseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first	0 (fully active) to 5 (dead)
Time to progression according to localized mRECIST and mRECIST	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)
2-year restricted mean survival time of overall survival	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
Changes in ALBI (albumin-bilirubin) grade	Baseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first
Best response within 2-years according to localized mRECIST and mRECIST	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 best response according to localized mRECIST and mRECIST	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)
Reason for subsequent HCC treatment	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)
Rate for conversion to curative resection and liver transplantation	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)
Changes in Child-Pugh class	Baseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first
Changes in health-related quality of life	Baseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first	EORTC QLQ-C30 and HCC18
Changes in regional liver function	Baseline up to 180 days after the initial treatment or subsequent anticancer treatment, whichever comes first	99mTc-MAA hepatobiliary scan with SPECT-CT
Progression-free survival	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	Time of treatment up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first	Common Terminology Criteria for Adverse Events v5.0
Changes in MELD (model for end-stage liver disease) score	Baseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first

Trial Locations

Locations (1)

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of