Bevacizumab and Erlotinib Hydrochloride in Treating Patients With Metastatic or Unresectable Biliary Tumors

PRIMARY OBJECTIVES:

I. Evaluate the objective response rate in patients with metastatic or unresectable cholangiocarcinoma treated with bevacizumab and erlotinib hydrochloride.

SECONDARY OBJECTIVES:

I. Evaluate time to progression in these patients.

II. Evaluate overall and progression-free survival of these patients.

III. Evaluate the adverse events associated with this regimen. OUTLINE: This is an open-label, multicenter study.

Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.

After completion of study therapy, patients are followed periodically for up to 3 years.

Criteria:

• Absolute neutrophil count >= 1,500/mm3
• Histologically or cytologically confirmed cholangiocarcinoma or gallbladder carcinoma:

• Metastatic or surgically unresectable disease
• Measurable disease, defined as >= 1 lesion whose longest diameter can be accurately measured as >= 2.0 cm with conventional techniques or as > 1.0 cm with spiral CT scan:

• Spiral CT scan imaging must be used for pre- and post-treatment tumor measurements of lesions measuring >= 1.0 cm to < 2.0 cm
• Clinical lesions will only be considered measurable when they are superficial

• Lesions on chest x-ray are acceptable as measurable lesions when they are clearly defined and surrounded by aerated lung
• No ampulla of Vater tumors
• No evidence of CNS disease
• Life expectancy >= 3 months
• ECOG performance status 0-2
• Platelet count >= 75,000/mm3
• Total bilirubin =< 2 times ULN
• ALT and AST =< 2.5 times ULN
• Creatinine =< 2 mg/dL
• Albumin >= 2.5 g/dL
• Alkaline phosphatase =< 5 times ULN
• Urine protein:creatinine ratio < 1.0 OR 24-hour urine protein < 1000 mg
• No concurrent illness or medical condition, including any of the following:

• Impairment of gastrointestinal (GI) function or disease that may significantly alter the absorption of erlotinib hydrochloride
• Requirement for IV alimentation
• No concurrent illness or medical condition, including any of the following:

• Active peptic ulcer disease;
• Serious or nonhealing wound, ulcer, or bone fracture;
• GI bleed that required procedural intervention within the past 3 months
• No concurrent illness or medical condition, including any of the following:

• Abdominal fistula, GI perforation, or intra-abdominal abscess within the past 28 days
• Ongoing or active infection
• Symptomatic congestive heart failure
• Psychiatric illness or social situation that would limit study compliance
• No other malignancy within the past 3 years
• No abnormalities of the cornea
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No clinically significant cardiovascular disease
• More than 4 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
• No significant traumatic injury within the past 28 days
• No prior systemic anticancer therapy for metastatic gallbladder or bile duct cancer
• More than 28 days since prior major surgery [Note: Insertion of a vascular access device is not considered major/minor surgery]
• More than 2 weeks since prior minor surgery [Note: Insertion of a vascular access device is not considered major/minor surgery]
• More than 7 days since prior core biopsy
• No concurrent major surgery
• No other concurrent chemotherapy, immunotherapy, radiotherapy, or any other therapy or supportive care considered investigational
• No concurrent enzyme-inducing antiepileptic drugs or any other CYP3A4 inducer, such as rifampin or Hypericum perforatum
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents or other concurrent anticancer therapies
• No concurrent prophylactic hematopoietic colony-stimulating factors
• Concurrent full-dose anticoagulants allowed provided PT/INR is > 1.5 and both of the following criteria are met:

• In-range INR on a stable dose of oral anticoagulant OR on a stable dose of low molecular weight heparin
• AND (continued from above) No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels, gastrointestinal ulcerations, or known varices)