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

June 13, 2017 updated by: National Cancer Institute (NCI)

Phase II and Pharmacodynamic Study of PS-341 in Patients With Unresectable or Metastatic Adenocarcinoma of the Bile Duct or Gallbladder

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111-2497
        • Fox Chase Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Arm I
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11.
Drug: bortezomib
Given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Disease Progression
Time Frame: Up to 1 year
Time from initiation of therapy to first progressive disease.
Up to 1 year
Overall Survival
Time Frame: Up to 1 year
The time from initiation of therapy to death or last follow-up.
Up to 1 year
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.
Once in the screening period (within 14 days of starting treatment)
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.
Once in the screening period (within 14 days of starting treatment)
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
Duration of study treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Steven Cohen, Fox Chase Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2004

Primary Completion (ACTUAL)

August 1, 2008

Study Completion (ACTUAL)

April 1, 2010

Study Registration Dates

First Submitted

June 10, 2004

First Submitted That Met QC Criteria

June 10, 2004

First Posted (ESTIMATE)

June 11, 2004

Study Record Updates

Last Update Posted (ACTUAL)

July 2, 2017

Last Update Submitted That Met QC Criteria

June 13, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2009-00046 (REGISTRY: CTRP (Clinical Trial Reporting Program))
  • CDR0000369715
  • 03-042 (Fox Chase Cancer Center)
  • 6135 (OTHER: CTEP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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