Bevacizumab and Erlotinib Hydrochloride in Treating Patients With Metastatic or Unresectable Biliary Tumors
Condition: Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Gastrointestinal Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer
MeSH terms: Cholangiocarcinoma; Gastrointestinal Neoplasms; Gallbladder Neoplasms; Bile Duct Neoplasms; Recurrence
Intervention: erlotinib hydrochloride; bevacizumab
Intervention description: Given orally, 150 mg, once daily.; Given IV, 5mg/kg on days 1 and 15 every cycle
Intervention MeSH terms: Bevacizumab; Antineoplastic Agents, Immunological; Erlotinib Hydrochloride; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 56.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving bevacizumab together with erlotinib
      hydrochloride works in treating patients with metastatic or unresectable biliary tumors.
      Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some
      block the ability of tumor cells to grow and spread. Others find tumor cells and help kill
      them or carry tumor-killing substances to them. Erlotinib hydrochloride may stop the growth
      of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab and
      erlotinib hydrochloride may also stop the growth of tumor cells by blocking blood flow to the
      tumor. Giving bevacizumab together with erlotinib hydrochloride may kill more tumor cells.
    

Eligibility criteria:

        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)