Efficacy Evaluation of TheraSphere to Treat Inoperable Liver Cancer With Blockage of the Portal Vein

The objective of this phase III, prospective randomized trial is to determine whether
TheraSphere provides a meaningful benefit in survival in comparison with the standard of care
(sorafenib) in patients with good hepatic function and advanced hepatocellular carcinoma
(HCC) associated with portal vein thrombosis (PVT).

This is an open-label prospective, multi-center, randomized, controlled clinical trial that
will evaluate the use of TheraSphere compared to standard-of-care sorafenib alone.

Inclusion Criteria:

- Patients over 18 years of age, regardless of race of gender

- Advanced unresectable hepatocellular carcinoma with branch portal vein thrombosis
(confirmed by non-invasive criteria EASL/AASLD, mandatory by histology in
non-cirrhotic patients); can be naive or recurrent HCC after curative treatment (> 6
months before randomization)

- Unilobar disease

- Child Pugh A

- Tumor volume ≤ 70% of liver volume (determined by visual estimation)

- At least one uni-dimensional HCC target lesion assessable by CT or MRI according to
RECIST 1.1

- ECOG Performance Status 0-1

- Platelets ≥ 50 X 10³/µL

- WBC ≥ 1.5 X10³/µL

- AST/ALT ≤ 5 X upper limit of normal

- Creatinine ≤ 2.0 mg/dL

- Life expectancy > 3 months

- Signed informed consent

Exclusion Criteria:

- Confirmed extra hepatic metastases. Patients with indeterminate hepatic hilar lymph
nodes up to 2.5 cm in greatest dimension, or with indeterminate lung nodules (single
lesion between 1-1.5 cm, or multiple smaller lesions with a total diameter ≤ 2 cm) may
be included if metastatic disease is deemed unlikely

- Known contraindication to standard-of-care sorafenib including allergic reaction, pill
swallowing difficulty, uncontrolled hypertension or history of cardiac disease,
significant GI bleed within 30 days, renal failure including dialysis

- Evidence of hepatic vein invasion or caval thrombosis

- Evidence of chronic obstructive pulmonary disease

- Indication for any possible curative treatment after multidisciplinary assessment
(surgery, ablation, transplantation)

- Previous treatment with sorafenib for more than 4 weeks during the previous 2 months;
prior sorafenib-related toxicity

- Initiation of anti-tumor therapy including chemotherapy or investigational drug
treatment within 30 days before beginning study

- Prior TACE < 6 months prior to screening phase in case of patients progressing from an
intermediate to an advanced stage due to occurrence of PVT

- Patients cannot be on a transplant list

- History of organ allograft

- Contraindications to angiography or selective visceral catheterization

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

- Prior external beam radiation therapy to the liver

- Evidence of continuing adverse effect of prior therapy

- Active GI bleeding and any bleeding diathesis or coagulopathy that is not correctable
by usual therapy or hemostatic agents

- Evidence of any disease or condition that would place the patient at undue risk and
preclude safe use of TheraSphere treatment

- Females of child-bearing potential must have a negative serum test Participation in
concurrent clinical trials