Phase II Study of Proton Beam Irradiation for the Treatment of Unresectable Hepatocellular Cancer and Cholangiocarcinoma

Inclusion Criteria:

- Biopsy proven unresectable or locally recurrent hepatocellular cancer or intrahepatic
cholangiocarcinoma. Patients with a single lesion must be 12cm or less in greatest
dimension. For patients with two lesions, no lesion may be greater than 10cm in
greatest dimension. For patients with three lesions, no lesion may be greater than
6cm in greatest dimension. Patients may have single or multinodular tumors (up to
3). There must be no evidence of extrahepatic tumor. Portal vein involvement or
thrombosis is allowed.

- Participants 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
20mm or greater with conventional techniques or as 10mm or greater with spiral CT
scan.

- Patients may have had prior chemotherapy, targeted biological therapy, surgery,
transarterial chemoembolization (TACE), radiofrequency ablation, or cryosurgery for
their disease as long as it is greater than 4 weeks from first protocol radiation
treatment (6 weeks for nitrosoureas or mitomycin C). Patients may not have had prior
radiation to the affected area.

- 18 years of age or older

- Expected survival must be greater than three months

- ECOG Performance Status of 0, 1 or 2

- Normal organ and marrow function as outlined in the protocol

- If patient has underlying cirrhosis, only Child-Pugh classification Group A or Group
B patients should be included in this study.

- Patients must be either surgically sterile or post-menopausal. Male and female
patients of child-bearing potential must agree to use adequate contraception prior to
study entry and for the duration of the study participation.

- Individuals with a history of other malignancies are eligible if they have been
disease-free for at least 5 years and are deemed by the investigator to be at low
risk for recurrence of that malignancy. Individuals with the following cancers are
eligible if diagnosed and treated within the past 5 years: cervical cancer in situ,
and basal cell or squamous cell carcinoma of the skin

Exclusion Criteria:

- Women who are pregnant or lactating

- Patients with evidence of non-hepatic metastatic disease

- Local conditions or systemic illnesses which would reduce the local tolerance to
radiation treatment, such as serious local injuries, active collagen vascular
disease, etc.

- Prior liver directed radiation treatment

- Patients may have no serious medical illness, which may limit survival to less than 3
months

- Patients may have no serious psychiatric illness/social situations which would limit
compliance with study requirements

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier

- Patients may not be receiving any other study agents

- Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia.