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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00085410
First received: June 10, 2004
Last updated: January 11, 2013
Last verified: January 2013
  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: Endpoint Classification: Efficacy Study
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 ] [ Designated as safety issue: No ]

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
  • VELCADE

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00085410

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

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00085410     History of Changes
Other Study ID Numbers: NCI-2009-00046, 03-042, N02CO12400
Study First Received: June 10, 2004
Last Updated: January 11, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Liver Neoplasms
Adenocarcinoma
Gallbladder Neoplasms
Bile Duct Neoplasms
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
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014