Selective Internal Radiation Therapy (SIRT) Using SIR-Spheres® Y-90 Resin Microspheres on DoR & ORR in Unresectable Hepatocellular Carcinoma Patients

Prior treatment

• Prior systemic anti-cancer therapy (including immunotherapy and/or targeted therapy), radiotherapy or use of other investigational agents for the treatment of HCC
• Incompetent biliary duct system, prior biliary intervention or a compromised Ampulla of Vater
• Evidence of potential delivery of mean radiation dose \> 30 Gy to the lungs (single treatment)
• Prior liver resection and/or liver transplant, with exception for patients with prior resection who meet inclusion criterion 6a
• Evidence of portal hypertension with ascites as seen on cross-sectional imaging or any history of prior variceal bleeding within 6 months prior to screening
• Patients with drug or alcohol dependency (within 6 months prior to study entry) in the opinion of the investigator

Other illness

• Patients eligible for ablation or resection for their malignancy, in the opinion of the investigator, at the time of screening
• Planned localized cancer treatment to the liver, other than the study treatment, throughout the duration of the study.
• Planned systemic cancer treatment throughout the duration of the study
• Patients with portal vein thrombosis
• Patients with extrahepatic disease
• Evidence that \< 33% of the total liver volume is disease-free and will be spared SIR-Spheres treatment
• Medical history of clotting disorders
• Underlying pulmonary disease requiring chronic oxygen therapy
• Active infection (hepatitis B (HBV) infection with ongoing HBV treatment and successfully treated hepatitis C infection are allowed)
• History of other cancer with current active treatment
• History of severe allergy or intolerance to contrast agents, narcotics, or sedatives
• Any condition that, in the opinion of the investigator, would interfere with safe delivery of the study treatment or with the interpretation of study results

Lab values

• Evidence of any detectable 99m Tc-macroaggregated albumin (99m Tc-MAA) flow outside of the liver in the abdomen, after application of established angiographic techniques to stop or mitigate such flow (e.g., placing catheter distal to gastric vessels or coiling)

Other

• Intrahepatic arteriovenous shunting (arteriovenous shunting resulting from a biopsy is allowed but must be embolized during the pre-treatment mapping procedure)
• Patients with contraindications to angiography and selective visceral catheterization
• Evidence of extrahepatic collateral supply to the tumor
• Female patients who are pregnant, breastfeeding, or premenopausal and unwilling to use an effective method of contraception through the 1-year follow-up; males unwilling to use effective method of contraception for 30 days post-procedure
• Concurrently enrolled in another study unless it is an observational, noninterventional study

• Willing, able, and mentally competent to provide written informed consent
• Age 18 or older at the time of consent
• All tumors must be measurable by CT or MRI according to localized mRECIST
• Life expectancy ≥ 6 months (to allow for adequate completion of study procedures and collection of data)
• Diagnosis of HCC with Liver Imaging Reporting and Data System (LIRADS) 4 or 5 or by histology
• Treatment-naïve patients or patients who have developed a new lesion following one of these prior locoregional treatments:
  • Liver resection with negative pathologic margins, no microvascular invasion, and no recurrence at resection margins for at least 6 months post-treatment and no new lesions within 6 months of liver resection
  • Ablation of a single ≤3cm lesion with no recurrence of the treated lesion for at least 6 months post-treatment
• BCLC stage A, B1, B2, and C with maximal single tumor size of ≤8 cm and sum of the maximal tumor dimensions of ≤12 cm with the entire tumor burden expected to be treatable within the perfused volume
• At least one lesion ≥1 cm in diameter (long axis) measured according to mRECIST criteria by CT or MRI
• Child-Pugh score of A5 or A6 at baseline
• Eastern Cooperative Oncology Group (ECOG) performance score of ≤1 at baseline
• Adequate blood count, liver enzymes, and renal function at baseline
  • Platelet count \>50,000/microliter (patients may not receive a platelet transfusion or growth factors to increase the platelet count so that the patient may be eligible for the study)
  • White Blood Cell (WBC) ≥ 3 x 10\^9/L
  • Hemoglobin \> 8.5 g/dL
  • Aspartate transaminase (AST) \& Alanine transaminase (ALT) \< 5 x upper limit normal
  • Bilirubin ≤ 2.0 mg/dL
  • Albumin \> 3.0 g/dL
  • International normalized ratio (INR) ≤ 2.0
  • Glomerular filtration rate (GFR) \> 50
• Negative serum pregnancy test at baseline
• Life expectancy of \> 3 months without any active treatment