Radioembolization as a Spearhead Treatment of Hepatocellular Carcinoma With Localized Portal Vein Tumor Thrombosis

Official title

An Open-label, Prospective, Multi-center Clinical Trial to Evaluate the Efficacy and Safety of Ablative Radioembolization Using Yttrium-90 Glass Microspheres in Patients With Locally-advanced Hepatocellular Carcinoma

Overview

The RESOLVE trial, an open-label, single-arm, multi-center study, aims to assess the efficacy and safety of ablative radioembolization using TheraSphere Yttrium-90 microspheres. This trial specifically targets patients diagnosed with hepatocellular carcinoma accompanied by localized portal vein tumor thrombosis (Vp1-Vp3) and who maintain good liver function.

Detailed description

Patients diagnosed with unilobar hepatocellular carcinoma and localized portal vein tumor thrombosis (Vp1-Vp3), who also exhibit good liver function, will undergo ablative radioembolization with a dose exceeding 205 Gy to the tumor using TheraSphere glass microspheres. These patients will be monitored over a two-year period to evaluate their clinical course, treatment outcomes, and safety.

Interventions

• Procedure Ablative radioembolization
  The interventional radiologist utilizes a pre-test with 99mTc-MAA SPECT-CT and cone-beam CT for procedural planning. For tumors confined to a single segment, the treatment area is planned to receive a radiation dose of over 400 Gy using the single-compartment MIRD technique. For tumors extending beyond a single segment, the multi-compartment MIRD technique is used to plan a radiation dose of 700 Gy (± 20%) to the tumor. The upper limit for the estimated lung dose is set at 25 Gy, and the upper l

Primary outcome measures

• Overall survival [Time frame: Time of treatment up to 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)]
• 2-year restricted mean survival time of overall survival [Time frame: Time of treatment up to 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)]
• Hepatic 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 unilobar hepatocellular carcinoma, either histologically and/or radiologically (LI-RADS 4 or 5)
• Patients with at least one measurable lesion greater than 10 mm on dynamic contrast-enhanced CT or MRI
• Patients with localized portal vein invasion limited in one lobe (Vp1-3) on dynamic contrast-enhanced CT or MRI
• Patients with no extrahepatic metastasis on lung CT and contrast-enhanced abdominal CT or MRI
• Patients with no prior treatment for liver cancer
• Child-Pugh class A
• Eastern Cooperative Oncology Group (ECOG) performance status of 1 or less
• Patients without serious dysfunction of major organs, as indicated by blood tests conducted 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 (transfusions allowed to meet this criterion)
• Total bilirubin ≤ 3.0 mg/dL
• Platelets ≥ 50,000/µL
• For patients not on anticoagulants, INR ≤ 2.0
• 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 fully understood the clinical trial and given written consent
• Female patients of childbearing age confirmed not to be pregnant

Exclusion criteria

• Patients unsuitable for ablative radioembolization as per the pre-test with macro-aggregated albumin labeled with technetium-99 (99mTc-MAA) for radioembolization.

• Cases where, according to multi-compartment Medical Internal Radiation Dose method, delivering 205 Gy of radiation to the tumor exceeds an estimated lung dose of 25 Gy.
• Cases with severe hepatic artery-portal vein shunting leading to expected irradiation of the non-tumorous opposite lobe.
• 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 with hepatic vein or bile duct invasion as seen on dynamic contrast-enhanced CT or MRI.
• Patients scheduled to use immunotherapy regardless of the response to radioembolization.
• Patients who had active cancer within two years prior to joining the clinical trial.
• Patients who have undergone surgery or procedures related to the bile duct.
• Pregnant or breastfeeding women.

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 · 4 centers

• National Cancer Center — Ilsan
• Seoul National University Hospital — Seoul
• Severance Hospital — Seoul
• Samsung Medical Center — Seoul

Publications

• Choi JW, Kim GM, Hyun D, Jang MJ, Kim HC. Radioembolization as a Spearhead Treatment of Hepatocellular Carcinoma with Localized Portal Vein Tumor Thrombosis (RESOLVE): Protocol for an Open-label, Multi-center, Single-arm Trial. Cardiovasc Intervent Radiol. 2025 Mar;48(3):398-404. doi: 10.1007/s00270-024-03935-2. Epub 2025 Feb 13. PMID 39948248

Identifiers

NCT: NCT06166576 · D-2306-207-1446

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗