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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Procedure: Ablative radioembolization using Yttrium-90 resin microspheres


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged 18 and over. Patients diagnosed with hepatocellular carcinoma histologically and/or radiologically (LI-RADS 4 or 5). Patients with no more than five lesions in dynamic contrast-enhanced CT or MRI, and the largest tumor diameter exceeding 8 cm. Patients without vascular invasion and bile duct invasion in dynamic contrast-enhanced CT or MRI. Patients with no extrahepatic metastasis in lung CT and contrast-enhanced abdominal CT or MRI. Patients with no prior treatment for liver cancer. Child-Pugh class A. ECOG performance status of 1 or less. Patients with no major organ dysfunction according to blood tests performed within one month of study enrollment. A. Leukocytes ≥ 2,500/µL and ≤ 12,000/µL B. Absolute neutrophil count ≥ 1,500 /mm^3 C. Hemoglobin ≥ 8.0 g/dL (transfusion allowed to meet this criterion) D. Total bilirubin ≤ 3.0 mg/dL E. Platelet ≥ 50,000/µL F. INR ≤ 2.0 for patients not taking anticoagulants G. AST ≤ 200 IU/L (i.e., ≤ 5X upper normal limit) H. ALT ≤ 200 IU/L (i.e., ≤ 5X upper normal limit) I. ALP ≤ 575 IU/L (i.e., ≤ 5X upper normal limit) J. Creatinine ≤ 2.0 mg/dL Patients with a life expectancy of more than 3 months. Patients who have adequately understood the clinical trial and consented in writing. Non-pregnant women of childbearing potential. Exclusion Criteria: - 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. A. 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. B. Cases with severe hepatic artery-portal vein shunting that might lead to irradiation of the non-tumorous liver segments. Patients whose volume of non-tumorous liver not included in the treatment area is less than 30% of the total non-tumorous liver volume. Patients scheduled to use immunotherapy irrespective of the response to radioembolization. Patients who have had active cancer within the last two years prior to the clinical trial participation. Patients who have undergone surgery or procedures related to the bile duct. Women who are pregnant or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label, prospective, single-arm, single-center trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ablative radioembolization for large HCC<br>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<br>* 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.<br>|

What is the study measuring?
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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 |
| --- | --- | --- |
| 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) | 
| 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) | 
| 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) | 
| 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 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 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular Carcinoma, Radioembolization