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

Overview

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.

Interventions

• 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 treatm

Primary outcome measures

• Objective response rate according to localized mRECIST [Time frame: 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 [Time frame: 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 (12)

• Objective response rate according to mRECIST. [Time frame: 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 frame: 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 frame: 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 frame: 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 frame: 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 frame: 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 frame: 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 frame: 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 frame: 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 frame: 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 frame: 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 frame: 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)]

Eligibility criteria

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.

• Leukocytes ≥ 2,500/µL and ≤ 12,000/µL
• Absolute neutrophil count ≥ 1,500 /mm\^3
• Hemoglobin ≥ 8.0 g/dL (transfusion allowed to meet this criterion)
• Total bilirubin ≤ 3.0 mg/dL
• Platelet ≥ 50,000/µL
• INR ≤ 2.0 for patients not taking anticoagulants
• AST ≤ 200 IU/L (i.e., ≤ 5X upper normal limit)
• ALT ≤ 200 IU/L (i.e., ≤ 5X upper normal limit)
• ALP ≤ 575 IU/L (i.e., ≤ 5X upper normal limit)
• 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.

• 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.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

South Korea · 1 center

• Seoul National University Hospital — Seoul

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 liv PMID 33433699
• 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 ap PMID 33166497
• 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. PMID 37866475

Identifiers

NCT: NCT06178198 · D-2306-208-1446 · NRF-2023R1A2C1006509

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗