Efficacy Evaluation of TheraSphere in Patients With Inoperable Liver Cancer

Inclusion Criteria:

- Signed informed consent prior to any study-related evaluation

- Male or female patients over 18 years of age

- Unresectable HCC confirmed by histology or by non-invasive AASLD criteria

- Measurable disease defined as at least one uni-dimensional measurable lesion by CT or
MRI according to RECIST 1.1

- Child Pugh score ≤ 7 points

- ECOG Performance Status score of ≤ 1

- Life expectancy of 12 weeks or more

- Eligible to receive standard-of-care sorafenib

- Platelet count of > 50 x 10⁹ or > 50% prothrombin activity

- Hemoglobin ≥ 8.5 g/dL

- Bilirubin ≤ 2.5 mg/dL

- ALT and AST< 5 X upper limit of normal

- Amylase and lipase ≤ 2X upper limit of normal

- Serum creatinine ≤ 1.5 X upper limit of normal

- INR < 2.0

Exclusion Criteria:

- Main portal vein thrombosis

- Eligible for curative treatment (ablation or transplantation)

- History of previous or concurrent cancer other than HCC unless treated curatively 5 or
more years prior to entry

- Confirmed presence of extra-hepatic disease except lung nodules and mesenteric or
portal lymph nodes ≤ 2.0 cm each

- Risk of hepatic or renal failure

- Tumor replacement > 70% of total liver volume based on visual estimation by
investigator OR tumor replacement >50% of total liver volume in the presence of
albumin <3 mg/dL

- History of severe allergy or intolerance to contrast agents, narcotics sedatives or
atropine that cannot be managed medically

- Contraindications to angiography and selective visceral catheterization

- Known contraindications to sorafenib including allergic reaction, pill-swallowing
difficulty, evidence of severe or systemic diseases, uncontrolled hypertension or
history of cardiac arrhythmias (requiring anti-arrhythmic therapy or pace maker),
congestive heart failure . New York Heart Association class 2, myocardial infarct
within 6 months, prolonged QT/QTc >450ms, or laboratory finding that in the view of
the investigator makes it undesirable for the patient to participate in the trial,
significant GI bleed within 30 days, metastatic brain disease, renal failure requiring
dialysis

- Taking any of the following: Rifampicin, St. John's Wort, phenytoin, carbamazepine,
phenobarbital, dexamethasone

- Taking any other systemic anticancer agent (docetaxel, doxorubicin, irinotecan)

- Taking any substrate agents for CYP 2B6 (bupropion, cyclophosphamide, efavirenz,
ifosfamide, methadone, paclitaxel, amodiaquine, repaglinide)

- Taking any UGT 1A1 and UGT 1A9 substrates (e.g. irinotecan)

- Taking P-Gp substrates (e.g. Digoxin)

- Prior liver resection must have taken >2 months prior to randomization

- Treatment with other locoregional therapies (other than study treatment) has not been
planned for the duration of the clinical study period

- Prior external beam radiation treatment to the liver or abdomen

- Prior yttrium-90 microsphere treatment to the liver

- Prior treatment with transarterial chemoembolization (TACE) or bland embolization >2
months prior to randomization and must have been applied to a treatment field and/or
lobe not targeted for treatment under this protocol

- Anti-cancer therapy or any treatment with an investigational agent within 30 days
prior to randomization

- Adverse effects due to prior therapy unresolved at randomization

- Prior systemic treatment for the treatment of HCC, including sorafenib

- Evidence of pulmonary insufficiency or clinically evident chronic obstructive
pulmonary disease

- Intervention for, or compromise of, the Ampulla of Vater

- Clinically evident ascites (trace ascites on imaging is acceptable)

- Pregnancy or breast feeding

- Women of child-bearing potential must have a negative serum pregnancy test within 14
days prior to randomization

- Disease or condition that would preclude safe use of TheraSphere, including concurrent
dialysis treatment, or unresolved serious infections including patients who are known
HIV positive

- Participation in concurrent clinical trials evaluating treatment intervention(s)