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

Gastrointestinal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00085410
• Other study ID #: NCI-2009-00046
• Secondary ID: 03-042N02CO12400
• Status: Completed
• Phase: Phase 2
• First received: June 10, 2004
• Last updated: January 11, 2013
• Start date: January 2004

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Extrahepatic Bile Duct
• Adenocarcinoma of the Gallbladder
• Advanced Adult Primary Liver Cancer
• Bile Duct Neoplasms
• Cholangiocarcinoma
• Gallbladder Neoplasms
• Gastrointestinal Cancer
• Gastrointestinal Neoplasms
• Liver Neoplasms
• 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

Intervention

Drug:
• bortezomib
Given IV

Locations

Country	Name	City	State
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with complete or partial response, evaluated using the international criteria proposed by the RECIST Committee		Up to 1 year	No