Radiation Major Hepatectomy to Selectively Treat Large Unifocal Hepatocellular Carcinoma (RESCUE)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Procedure: Ablative radioembolization using Yttrium-90 resin microspheres

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 Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jin Woo Choi, MD, PhD; Phone Number: +82-220722584; Email: jwchoi.med@snu.ac.kr

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
    • Contact: Jin Woo Choi, MD, PhD
    • Contact: Jin Woo Choi, MD, PhD; Phone Number: +82-220722584; Email: jwchoi.med@snu.ac.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

Procedure: Ablative radioembolization using Yttrium-90 resin microspheres; Based on 99mTc-MAA mapping, a partition model (multi-compartment MIRD) is employed to plan for a radiation dose of 400 (± 30%) to the tumor. If delivering this dose to the tumor is challenging due to lung dose limitations, the maximum feasible dose is administered to the tumor while maintaining the estimated lung dose below 15 Gy. While treating the entire tumor with a single high-dose radioembolization session is preferred, if necessary due to considerations like estimated lung dose, the treatment can be divided into two sessions, keeping the cumulative lung dose below 25 Gy. For any methods not covered in this discussion, refer to the SIR-Sphere user manual by Sirtex.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate according to localized mRECIST	The number of patients with partial or complete response as the best local response divided by the total number of participants	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 localized mRECIST	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	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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
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)
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)
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)
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
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)
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)
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)
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)
Adverse event and serious adverse event	Common Terminology Criteria for Adverse Events v5.0	Time of treatment up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first
Changes in Child-Pugh class		Baseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first
Changes in ALBI (albumin-bilirubin) grade		Baseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first
Changes in ECOG (Eastern Cooperative Oncology Group) performance status scale	0 (fully active) to 5 (dead)	Baseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first
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)
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)
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
Changes in health-related quality of life	EORTC QLQ-C30 and HCC18	Baseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first
Changes in regional liver function	99mTc-MAA hepatobiliary scan with SPECT-CT	Baseline up to 180 days after the initial treatment or subsequent anticancer treatment, whichever comes first

Other Outcome Measures

Outcome Measure	Time Frame
Pre-treatment dosimetry based on 99mTc-MAA SPECT-CT	Baseline
Post-treatment dosimetry based on Y90 PET-CT	Within two days after the procedure

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Study Chair: Jin Woo Choi, MD, PhD, Seoul National University Hospital

Publications and helpful links

General Publications

• Levillain H, Bagni O, Deroose CM, Dieudonne A, Gnesin S, Grosser OS, Kappadath SC, Kennedy A, Kokabi N, Liu DM, Madoff DC, Mahvash A, Martinez de la Cuesta A, Ng DCE, Paprottka PM, Pettinato C, Rodriguez-Fraile M, Salem R, Sangro B, Strigari L, Sze DY, de Wit van der Veen BJ, Flamen P. International recommendations for personalised selective internal radiation therapy of primary and metastatic liver diseases with yttrium-90 resin microspheres. Eur J Nucl Med Mol Imaging. 2021 May;48(5):1570-1584. doi: 10.1007/s00259-020-05163-5. Epub 2021 Jan 12.
• Garin E, Tselikas L, Guiu B, Chalaye J, Edeline J, de Baere T, Assenat E, Tacher V, Robert C, Terroir-Cassou-Mounat M, Mariano-Goulart D, Amaddeo G, Palard X, Hollebecque A, Kafrouni M, Regnault H, Boudjema K, Grimaldi S, Fourcade M, Kobeiter H, Vibert E, Le Sourd S, Piron L, Sommacale D, Laffont S, Campillo-Gimenez B, Rolland Y; DOSISPHERE-01 Study Group. Personalised versus standard dosimetry approach of selective internal radiation therapy in patients with locally advanced hepatocellular carcinoma (DOSISPHERE-01): a randomised, multicentre, open-label phase 2 trial. Lancet Gastroenterol Hepatol. 2021 Jan;6(1):17-29. doi: 10.1016/S2468-1253(20)30290-9. Epub 2020 Nov 7.
• Choi JW, Suh M, Paeng JC, Kim JH, Kim HC. Radiation Major Hepatectomy Using Ablative Dose Yttrium-90 Radioembolization in Patients with Hepatocellular Carcinoma 5 cm or Larger. J Vasc Interv Radiol. 2024 Feb;35(2):203-212. doi: 10.1016/j.jvir.2023.10.011. Epub 2023 Oct 21.

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2023
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: November 30, 2023
• First Submitted That Met QC Criteria: December 11, 2023
• First Posted (Actual): December 20, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 5, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Radioembolization
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: D-2306-208-1446; NRF-2023R1A2C1006509 (Other Grant/Funding Number: National Research Fund of Korea)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No