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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 terminated.
(The trial was discontinued early due to no confirmed partial responses.)
Sponsor:
ClinicalTrials.gov Identifier:
NCT00085410
First Posted: June 11, 2004
Last Update Posted: July 2, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
  Purpose
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: None (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:
  • Objective Response Rate [ Time Frame: Up to 1 year ]
    Objective Response Rate (ORR) was determined by best response on radiologic assessment (computed tomography or magnetic resonance imaging) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0.


Secondary Outcome Measures:
  • Time to Disease Progression [ Time Frame: Up to 1 year ]
    Time from initiation of therapy to first progressive disease.

  • Overall Survival [ Time Frame: Up to 1 year ]
    The time from initiation of therapy to death or last follow-up.

  • Correlation of the Degree of Proteasome Inhibition in Peripheral Blood With the Degree of Proteasome Inhibition in Tumor Specimens [ Time Frame: Once in the screening period (within 14 days of starting treatment) ]
    Proteasome inhibition compared between tumor specimens and peripheral blood. Sufficient tissue samples are required for this analysis.

  • Correlation of Phenotypic Expression of NF-kB, p53, and Other Molecular Markers in Biliary Washings and Tumor Biopsies With Clinical Outcomes [ Time Frame: Once in the screening period (within 14 days of starting treatment) ]
    Evaluation of clinical outcomes with expression of molecular markers specified and others. Sufficient amount of biliary washings and tumor biopsies needed for analysis.

  • Correlation of Treatment With Changes in Phenotypic Expression of Molecular Markers [ Time Frame: Duration of study treatment ]
    Phenotypic expression of molecular markers before and after study treatment


Enrollment: 20
Study Start Date: January 2004
Study Completion Date: April 2010
Primary Completion Date: August 2008 (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

Detailed Description:

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00085410


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

Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00085410     History of Changes
Other Study ID Numbers: NCI-2009-00046
NCI-2009-00046 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000369715
03-042
03-042 ( Other Identifier: Fox Chase Cancer Center )
6135 ( Other Identifier: CTEP )
First Submitted: June 10, 2004
First Posted: June 11, 2004
Results First Submitted: July 9, 2013
Results First Posted: June 14, 2017
Last Update Posted: July 2, 2017
Last Verified: June 2017

Additional relevant MeSH terms:
Adenocarcinoma
Liver Neoplasms
Gallbladder Neoplasms
Bile Duct Neoplasms
Cholangiocarcinoma
Gastrointestinal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Biliary Tract Neoplasms
Biliary Tract Diseases
Gallbladder Diseases
Bile Duct Diseases
Gastrointestinal Diseases
Bortezomib
Antineoplastic Agents