Bortezomib in Treating Patients With Unresectable Locally Advanced or Metastatic Adenocarcinoma of the Bile Duct or Gallbladder

Inclusion Criteria:

• Absolute neutrophil count >= 1,500/mm3
• No psychiatric illness or social situation that would preclude study compliance
• Chemotherapy administered solely as a radiosensitizer or as adjuvant therapy and investigational or targeted therapies (i.e., inhibitors of the epidermal growth factor receptor) will not count toward the maximum of 2 prior regimens allowed

• Histologically or cytologically confirmed adenocarcinoma of the intrahepatic or extrahepatic bile duct or gallbladder:

  • Locally advanced or metastatic disease
• At least 1 unidimensionally measurable lesion >=20 mm by conventional techniques OR >= 10 mm by spiral CT scan
• Not amenable to curative surgical resection
• No known brain metastases

• Performance status:

  • ECOG 0-2

• Life expectancy:

  • More than 12 weeks
• Platelet count >= 100,000/mm3
• WBC >= 3,000/mm3
• AST and ALT ≤ 2.5 times upper limit of normal (ULN) [Note: Biliary shunting or stenting allowed to achieve the required bilirubin and transaminase levels]
• Bilirubin ≤ 1.5 times ULN [Note: Biliary shunting or stenting allowed to achieve the required bilirubin and transaminase levels]
• Creatinine within ULN OR Creatinine clearance >= 60 mL/min
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No symptomatic cardiac arrhythmia within the past 4 weeks
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No underlying neuropathy >= grade 2
• No history of allergic reaction to boron, mannitol, or bortezomib
• No active or ongoing infection
• No concurrent uncontrolled illness
• No medical or psychiatric condition that would preclude study participation
• No prophylactic granulocyte or platelet growth factors (filgrastim [G-CSF] or sargramostim [GM-CSF])
• Prior chemotherapy as a radiosensitizer (e.g., fluorouracil or gemcitabine) with radiotherapy is allowed as adjuvant therapy after resection for locally advanced disease provided there is evidence of disease progression
• No more than 2 prior chemotherapy regimens for locally advanced or metastatic disease
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer agents or therapies
• No other concurrent investigational agents