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

Phase 2
Recruiting
Conditions
Hepatocellular Carcinoma
Interventions
Procedure: Ablative radioembolization
Registration Number
NCT06166576
Lead Sponsor
Seoul National University Hospital
Brief Summary

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
30
Inclusion Criteria
  1. Adults aged 18 and over

  2. Patients diagnosed with unilobar hepatocellular carcinoma, either histologically and/or radiologically (LI-RADS 4 or 5)

  3. Patients with at least one measurable lesion greater than 10 mm on dynamic contrast-enhanced CT or MRI

  4. Patients with localized portal vein invasion limited in one lobe (Vp1-3) on dynamic contrast-enhanced CT or MRI

  5. Patients with no extrahepatic metastasis on lung CT and contrast-enhanced abdominal CT or MRI

  6. Patients with no prior treatment for liver cancer

  7. Child-Pugh class A

  8. Eastern Cooperative Oncology Group (ECOG) performance status of 1 or less

  9. Patients without serious dysfunction of major organs, as indicated by blood tests conducted 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 (transfusions allowed to meet this criterion)
    4. Total bilirubin ≤ 3.0 mg/dL
    5. Platelets ≥ 50,000/µL
    6. For patients not on anticoagulants, INR ≤ 2.0
    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 fully understood the clinical trial and given written consent

  12. Female patients of childbearing age confirmed not to be pregnant

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

    1. 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.
    2. Cases with severe hepatic artery-portal vein shunting leading to expected irradiation of the non-tumorous opposite lobe.
  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 with hepatic vein or bile duct invasion as seen on dynamic contrast-enhanced CT or MRI.

  4. Patients scheduled to use immunotherapy regardless of the response to radioembolization.

  5. Patients who had active cancer within two years prior to joining the clinical trial.

  6. Patients who have undergone surgery or procedures related to the bile duct.

  7. Pregnant or breastfeeding women.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
RadioembolizationAblative radioembolizationHepatocellular carcinoma with localized portal vein tumor thrombosis (Vp1-Vp3) will be treated by ablative radioembolization using TheraSphere (Boston Scientific) glass microspheres
Primary Outcome Measures
NameTimeMethod
Overall survivalTime 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
NameTimeMethod
Objective response rate according to mRECISTTime 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 mRECISTTime 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 mRECISTTime 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 mRECISTTime 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)
Progression-free survivalTime 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 survivalTime 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 mRECISTTime 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 mRECISTTime 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 mRECISTTime 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 mRECISTTime 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 treatmentTime 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 mRECISTTime 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

Time to progression according to localized mRECIST and mRECISTTime 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 survivalTime of treatment up to participant's death, opposition to data collection, lost to follow-up, or 24 months the initial treatment
Rate for conversion to curative resection and liver transplantationTime 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 ALBI (albumin-bilirubin) gradeBaseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first
Changes in ECOG (Eastern Cooperative Oncology Group) performance status scaleBaseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first

0 (fully active) to 5 (dead)

Time to subsequent HCC treatmentTime 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 classBaseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first
Objective response rate according to localized mRECISTTime 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

Pathological necrosis rate (%) after curative resection or liver transplantationTime 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 eventTime 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) scoreBaseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first

Trial Locations

Locations (4)

National Cancer Center

🇰🇷

Ilsan, Gyeonggi-do, Korea, Republic of

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

Severance Hospital

🇰🇷

Seoul, Korea, Republic of

Samsung Medical Center

🇰🇷

Seoul, Korea, Republic of

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