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

NCT ID: NCT00085410

Last Updated: 2017-07-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-01-31
• Study Completion Date: 2010-04-30

Brief 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.

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11.

Group Type: EXPERIMENTAL

bortezomib

Intervention Type: DRUG

Given IV

Interventions

bortezomib

Given IV

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven Cohen

Role: PRINCIPAL_INVESTIGATOR

Fox Chase Cancer Center

Locations

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Countries

United States

References

Denlinger CS, Meropol NJ, Li T, Lewis NL, Engstrom PF, Weiner LM, Cheng JD, Alpaugh RK, Cooper H, Wright JJ, Cohen SJ. A phase II trial of the proteasome inhibitor bortezomib in patients with advanced biliary tract cancers. Clin Colorectal Cancer. 2014 Jun;13(2):81-6. doi: 10.1016/j.clcc.2013.12.005. Epub 2014 Jan 4.

Reference Type: RESULT

PMID: 24512954 (View on PubMed)

Other Identifiers

NCI-2009-00046

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000369715

Identifier Type: -

Identifier Source: secondary_id

03-042

Identifier Type: -

Identifier Source: secondary_id

03-042

Identifier Type: OTHER

Identifier Source: secondary_id

6135

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2009-00046

Identifier Type: -

Identifier Source: org_study_id