Clinical trial NCT06166576: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular carcinoma
Radioembolization
Portal vein tumor thrombosis
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2023-12-12
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall survival
timeFrame: 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 outcomes:
measure: Objective response rate according to mRECIST
timeFrame: 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)
measure: Duration of response according to mRECIST
timeFrame: 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)
measure: 2-year restricted mean duration of response according to localized mRECIST and mRECIST
timeFrame: 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
measure: Complete response rate according to localized mRECIST and mRECIST
timeFrame: 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)
measure: Duration of complete response according to localized mRECIST and mRECIST
timeFrame: 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)
measure: 2-year restricted mean DoCR (RMDoCR) according to localized mRECIST and mRECIST
timeFrame: 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
measure: Best response within 2-years according to localized mRECIST and mRECIST
timeFrame: 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)
measure: Time to best response according to localized mRECIST and mRECIST
timeFrame: 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)
measure: Time to progression according to localized mRECIST and mRECIST
timeFrame: 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)
measure: 2-year restricted mean survival time of overall survival
timeFrame: Time of treatment up to participant's death, opposition to data collection, lost to follow-up, or 24 months the initial treatment
measure: Progression-free survival
timeFrame: 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)
measure: Hepatic progression-free survival
timeFrame: 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)
measure: Pathological necrosis rate (%) after curative resection or liver transplantation
timeFrame: 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)
measure: Time to subsequent HCC treatment
timeFrame: 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)
measure: Reason for subsequent HCC treatment
timeFrame: 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)
measure: Rate for conversion to curative resection and liver transplantation
timeFrame: 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)
measure: Adverse event and serious adverse event
timeFrame: Time of treatment up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first
measure: Changes in Child-Pugh class
timeFrame: Baseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first
measure: Changes in ALBI (albumin-bilirubin) grade
timeFrame: Baseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first
measure: Changes in MELD (Model for end-stage liver disease) score
timeFrame: Baseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first
measure: Changes in ECOG (Eastern Cooperative Oncology Group) performance status scale
timeFrame: Baseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first
measure: Objective response rate according to localized mRECIST
timeFrame: 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)
measure: Duration of response according to localized mRECIST
timeFrame: 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)
Other outcomes:
measure: Pre-treatment dosimetry based on 99mTc-MAA SPECT-CT
timeFrame: Baseline
measure: Post-treatment dosimetry based on Y90 PET-CT
timeFrame: Within two days after the procedure
Locations:
city: Ilsan
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Seoul National University Hospital
name: Jin Woo Choi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: