Study Of Intrahepatic Arterial Injection of 90-Y Glass Microspheres for Cholangiocarcinoma

The goal of treatment with TheraSphere is to allow a large dose of radiation to be delivered
directly to the tumor with less risk of toxic effects from radiation to other parts of the
body or to healthy liver tissue when compared with currently available treatments.

The standard treatment for cholangiocarcinoma is surgery (if possible), external beam
radiation therapy and/or chemotherapy. External beam radiation therapy to the liver may
reduce symptoms, but only 20% of patients experience significant tumor shrinkage.
Chemotherapy has response rates ranging from 6-19%. More recently, a new approach has been
developed, called TheraSphere. Based on the results of earlier studies with TheraSphere, the
study doctors at Moffitt feel this is a reasonable alternative to the standard treatment for
this disease.

TheraSphere has restricted approval from the United States Food and Drug Administration
(FDA) for the treatment of hepatocellular liver cancer; but it has not yet been approved for
the treatment of cholangiocarcinoma. TheraSphere is a medical device containing yttrium-90
(Y-90), a radioactive material that has been used previously in the treatment of liver
tumors. Y-90 is incorporated into very tiny glass beads called microspheres and is injected
into the liver through the blood vessels supplying the liver.

Inclusion Criteria:

- Patients must have newly diagnosed or recurrent (post surgery) histologically or
cytologically proven cholangiocarcinoma.

- Patients can have solitary, multifocal unilobar, or bilobar disease without evidence
of extrahepatic involvement. Patients must have measurable disease, defined as at
least one lesion that can be accurately measured in at least one dimension (longest
diameter to be recorded) as >10 mm with spiral computed tomography (CT) scan or
magnetic resonance imaging (MRI).

- Age >18 years

- Life expectancy of greater than 3 months based on physician judgment

- Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to
2 (Karnofsky 50%)

- No prior chemotherapy or radiation treatment for cholangiocarcinoma

- Childs-Pugh score A or Childs-Pugh score B without portal vein thrombus

- Lung shunting that predicts lung dose to be <30 Gy in a single treatment

- The effects of TheraSpheres on the developing human fetus at the recommended
therapeutic dose are unknown. For this reason and because radioactive spheres are
known to be teratogenic, women of child-bearing potential and men must agree to use
adequate contraception (hormonal or barrier method of birth control; abstinence)
prior to study entry and for the duration of study participation. Should a woman
become pregnant or suspect she is pregnant while participating in this study, she
should inform her treating physician immediately.

- Ability to understand and the willingness to sign a written informed consent document

- Adequate baseline hematopoietic function:

- total white blood cell count equal to or greater than 3,000/mm³

- absolute granulocyte count greater than 1,500/mm³

- platelet count equal to or greater than 100,000/mm³

- Hemoglobin >8.0

Exclusion Criteria:

- Patients receiving any other investigational agents

- Patients with extrahepatic disease

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Pregnant women are excluded from this study because TheraSpheres are radioactive and
radiation is a known agent with the potential for teratogenic or abortifacient
effects. Because there is an unknown but potential risk for adverse events in nursing
infants secondary to treatment of the mother with TheraSpheres, breastfeeding should
be discontinued if the mother is treated with TheraSpheres.

- Patients with immune deficiency are at increased risk of lethal infections when
treated with marrow-suppressive therapy. In addition, antiretrovirals are known
radiation sensitizers and could dramatically increase the risk of fulminant hepatic
failure. Therefore, HIV-positive patients are excluded from the study because of
possible lethal side effects.

- Bulk disease (tumor volume > 70% of the target liver volume, or tumor nodules too
numerous to count)

- Aspartic transaminase (AST) or alanine transaminase (ALT) > 5 times upper limit of
normal (ULN)

- Bilirubin > 2 mg/dL

- Child-Pugh C Liver Cirrhosis

- Tumor volume > 50% combined with an albumin < 3 g/dL

- Complete occlusion of main portal vein causing portal hypertension