Yttrium-90 Radioembolization for Cirrhosis-Associated Thrombocytopenia

This protocol will provide access to TheraSphere® treatment for patients who have refractory
thrombocytopenia secondary to cirrhosis. This protocol will utilize splenic artery-directed
TheraSphere® treatment.

Inclusion Criteria:

- Male or female, 18 years of age or older, of any ethnic or racial group.

- Diagnosis of cirrhosis or portal hypertension with a serum platelet count less than or
equal to 80 × 109/L. [Rationale: platelet count <100 × 109/L triples the rate of
liver-related adverse events (3) and worsens postoperative survival in the setting of
hepatocellular carcinoma (HCC) (4). Initial platelet count of 80 × 109/L can allow the
majority of patients who successfully respond to 90Y-RE (clinical endpoint of 50%
platelet count increase) to exceed the 100 × 109/L threshold.]

Cirrhosis is defined by one of three criteria:

- Liver Biopsy/histology consistent with cirrhotic architectural liver changes

- Portal hypertension (Hepatic venous pressure gradient ≥10 mm Hg)

- Evidence of esophageal and/or gastric varices

- Patients must have evidence of splenomegaly as determined by screening cross-sectional
imaging.

- No evidence of myelosuppression (e.g. lymphopenia) as evidenced by normal hematology
values at Screening

- Adequate baseline organ function(with the exception of cirrhosis) as evidenced by
normal BUN/Cr and electrolytes on screening chemistry.

- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-2

- Patient has a life expectancy of greater than 6 months without intervention.

- Patient is willing to participate in the study and has signed the study informed
consent.

- Women of childbearing potential must have a negative serum pregnancy test within 28
days prior to screening and must not be breastfeeding.

Exclusion Criteria:

- Patients with serum platelet count less than 10 × 109/L.

- History of bleeding disorder attributed to another cause other than cirrhosis (e.g.
Von Willebrand disease)

- Declines or unable to provide informed consent

- History of prior partial splenic embolization (PSE) or splenectomy

- Use of any medication known to increase platelet count 1 month prior to Baseline.

- History of allergy or sensitivity to TheraSphere® or its components.

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

- Contraindications to angiography and selective visceral catheterization such as
bleeding, diathesis or coagulopathy that is not correctable by usual therapy or
hemostatic agents (e.g. closure device)

- Previous randomization in a trial using 90Y RE

- Patient must not have participated or enrolled in a clinical trial with an
investigational device / therapy within 30 days prior to randomization

- Any serious medical condition likely to impede successful completion of the study,
such as certain mental disorders, cardiac arrhythmias, and uncontrolled congestive
heart failure or respiratory disease.

- Patients actively on chemotherapy.