Sorafenib Tosylate and Erlotinib Hydrochloride in Treating Patients With Locally Advanced, Unresectable, or Metastatic Gallbladder Cancer 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