Phase II Study of Sorafenib (NSC-724772) and Erlotinib (NSC-718781) in Patients With Advanced Gallbladder Carcinoma or Cholangiocarcinoma

Inclusion Criteria:

- Cytologically or pathologically confirmed gallbladder carcinoma or cholangiocarcinoma

- No ampullary carcinoma

- Locally advanced unresectable or distant metastatic disease

- Measurable disease

- Patients with biliary obstruction must have decompression of the biliary tree by ERCP
and stenting or percutaneous drainage

- No prior systemic treatment for metastatic or unresectable locally advanced disease

- No known brain metastases

- Zubrod performance status of 0-1

- Leukocyte count ≥ 3,000/mm^3

- ANC ≥ 1,000/mm^3

- Platelet count ≥100,000/mm^3

- Total serum bilirubin ≤ 1.5 times upper limit of normal (ULN)

- For patient who had decompression of the biliary tree within the past 14 days,
stability of the bilirubin level needs to be confirmed with two measurements
within 5 to 7 days of each other

- Serum albumin ≥ 2.5 g/dL

- AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN for liver metastases)

- Creatinine clearance ≥ 60 mL/min

- Not pregnant or nursing

- Fertile patients must agree to use effective contraception

- No active biliary sepsis

- No bleeding diathesis

- No uncontrolled or clinically significant cardiovascular disease, including any of
the following:

- Myocardial infarction within the past 6 months

- Uncontrolled angina within the past 6 months

- NYHA class II-IV congestive heart failure

- Grade 3 cardiac valve dysfunction

- Cardiac arrhythmia not controlled by medication

- History of stroke or transient ischemic attack within the past 6 months

- History ofarterial thrombotic event of any type in the past 6 months

- No uncontrolled hypertension, as evidenced by systolic BP ≥ 150 mm Hg or diastolic BP
≥ 100 mm Hg, within the past 28 days

- Must be able to swallow and tolerate oral medications

- No gastrointestinal tract disease or prior abdominal surgery that results in an
inability to absorb oral medication

- No other prior malignancy except adequately treated basal cell or squamous cell skin
cancer, in situ cervical cancer, adequately treated stage I or II cancer from which
the patient is currently in complete remission, or any other cancer from which the
patient has been disease-free within the past 3 years

- No concurrent grapefruit or its juice

- At least 6 months since 1 adjuvant or neoadjuvant regimen of chemotherapy, hormonal
therapy, immunotherapy, radiotherapy (to < 25% of bone marrow only), or
chemoradiotherapy before documented recurrence or metastatic disease

- No prior treatment with any antiangiogenic agent or any EGFR inhibitors for any
reason

- Concurrent multiple anti-hypertensive medications allowed

- No plans to receive concurrent chemotherapy, hormonal therapy, radiotherapy,
immunotherapy, or any other therapy, including herbal or alternative medications for
treatment of cancer