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