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

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

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.

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.

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.