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

This study has been completed.
Information provided by (Responsible Party):
National Cancer Institute (NCI) Identifier:
First received: June 10, 2004
Last updated: January 11, 2013
Last verified: January 2013
This phase II trial is studying how well bortezomib works as first-line systemic therapy in treating patients with unresectable locally advanced or metastatic adenocarcinoma (cancer) of the bile duct or gallbladder. Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for their growth

Condition Intervention Phase
Adenocarcinoma of the Extrahepatic Bile Duct
Adenocarcinoma of the Gallbladder
Advanced Adult Primary Liver Cancer
Gastrointestinal Cancer
Localized Unresectable Adult Primary Liver Cancer
Recurrent Adult Primary Liver Cancer
Recurrent Extrahepatic Bile Duct Cancer
Recurrent Gallbladder Cancer
Unresectable Extrahepatic Bile Duct Cancer
Unresectable Gallbladder Cancer
Drug: bortezomib
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II and Pharmacodynamic Study of PS-341 in Patients With Unresectable or Metastatic Adenocarcinoma of the Bile Duct or Gallbladder

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Proportion of patients with complete or partial response, evaluated using the international criteria proposed by the RECIST Committee [ Time Frame: Up to 1 year ]

Enrollment: 35
Study Start Date: January 2004
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11.
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341

Detailed Description:


I. Determine the objective response rate in patients with unresectable locally advanced or metastatic adenocarcinoma of the bile duct or gallbladder treated with bortezomib.


I. Determine the time to disease progression in patients treated with this drug.

II. Determine the overall survival of patients treated with this drug. III. Correlate the degree of proteasome inhibition in peripheral blood with degree of proteasome inhibition in tumor specimens of patients treated with this drug.

IV. Correlate phenotypic expression of NF-kB, p53, and other molecular markers in biliary washings and tumor biopsies with clinical outcomes in patients treated with this drug.

V. Correlate treatment with this drug with changes in phenotypic expression of molecular markers in these patients.

OUTLINE: This is an open-label, multicenter study.

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
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Please refer to this study by its identifier: NCT00085410

United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111-2497
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Steven Cohen Fox Chase Cancer Center
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI) Identifier: NCT00085410     History of Changes
Other Study ID Numbers: NCI-2009-00046
N02CO12400 ( Other Grant/Funding Number: US NIH Grant/Contract Award Number )
Study First Received: June 10, 2004
Last Updated: January 11, 2013

Additional relevant MeSH terms:
Liver Neoplasms
Gastrointestinal Neoplasms
Bile Duct Neoplasms
Gallbladder Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Gastrointestinal Diseases
Biliary Tract Neoplasms
Bile Duct Diseases
Biliary Tract Diseases
Gallbladder Diseases
Antineoplastic Agents processed this record on May 23, 2017