Cyberknife Radiosurgery Boost for Hilar Cholangiocarcinoma (Klatskin Tumor)

This is a dose escalation study which will escalate the dose of Cyberknife radiosurgery
boost after external beam radiation of 45 Gy with concurrent capecitabine. The three dose
levels are 4 Gy x5, 5 Gy x5 and 6 Gy x 5, with 3 patients at each dose level. Dose-limiting
toxicity (DLT) is defined as acute grade 3 liver or intestinal toxicity or any acute grade 4
toxicity. If one patient experienced a DLT at a particular dose level, the cohort should be
expanded to 6 patients. The maximum tolerated dose (MTD) is defined as the dose level below
that which results in DLT in 2 or more of the 6 patients in each cohort. At least 5 patients
should be enrolled in the cohort of 6 Gy x 5 even if none of the first 3 experienced DLT, as
a means of added verification of dose tolerance, at this upper limit of dose for this study.

The patient population includes any patients who have unresectable hilar cholangiocarcinoma
without any prior history of radiation. We anticipate accruing 1 patient every 2 months;
therefore, we estimate that it will require approximately 22 months to accrue 11 patients if
no DLT is experienced by any patients requiring expansion of the cohorts.

Inclusion Criteria:

- Age eighteen years or older

- Histological defined unresectable cholangiocarcinoma of hilar region of the liver

- Patients should have evaluable disease on one or more imaging modalities (CT scan,
MRI, and/or PET) since this will be necessary for radiation treatment planning.
However, because the borders of these tumors are sometimes difficult to define
precisely, measurable disease is not required (see Section 9.1 for definitions of
evaluable and measurable disease).

- The maximum tumor dimension should be less than 6 cm.

- Patients with pathologically enlarged perihepatic regional lymph nodes are allowed.

- Prior surgical resection is allowed if there is gross disease remaining

- Adjuvant chemotherapy is allowed at least 1 month after completion of radiation
therapy if any grade 3 or higher toxicity has resolved

- Percutaneous biliary drains and biliary stents are allowed

- Performance status of ECOG 0-1 (see Appendix I)

- Life expectancy greater than 6 months

- Subject must have normal organ and marrow functions as defined below

- leukocytes >3,000/mcL

- absolute neutrophil count >1,500/mcL

- platelets >100,000/mcL

- total bilirubin <2.5 X institutional upper limit of normal

- AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal

- creatinine within normal institutional limits OR

- creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels
above institutional normal.

- PT/PTT within normal institutional limits

- Gold marker seeds (1 to 3) are required to be placed in or around the primary tumor
by an interventional radiologist

- Ability to give written informed consent and willingness to comply with the
requirements of the protocol

- Women of child-bearing potential must agree to use an effective method of birth
control during treatment and for six months after receiving their last dose of
treatment

Exclusion Criteria:

- Patients who have had prior chemotherapy

- Patients who have had external beam radiation to the region of liver hilar
previously.

- Patients receiving any other investigational agents

- Patients with known metastases

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to capecitabine.

- 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.

- Patients who are not candidates for gold marker seeds placement due to position of
the tumor or co-existing medical condition.

- Pregnant or lactating women and women of child-bearing potential who are not using an
effective method of birth control

- Any condition that compromises compliance with the objectives and procedures of this
protocol, as judged by the principal investigator