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

Phase 2

Terminated

• Conditions: Localized Unresectable Adult Primary Liver Cancer; Advanced Adult Primary Liver Cancer; Gastrointestinal Cancer; Adenocarcinoma of the Extrahepatic Bile Duct; Recurrent Adult Primary Liver Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer; Adenocarcinoma of the Gallbladder; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer
• Interventions: Drug: bortezomib

• Registration Number: NCT00085410
• Lead Sponsor: National Cancer Institute (NCI)

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.

Study Timeline

• Study Start: 2004-01
• Study First Submitted: 2004-06-10
• Study First Submitted QC: 2004-06-10
• Study First Posted: 2004-06-11
• Primary Completion: 2008-08
• Study Completion: 2010-04
• Results First Submitted: 2013-07-09
• Results First Submitted QC: 2017-05-15
• Status Verified: 2017-06
• Last Update Submitted: 2017-06-13
• Results First Posted: 2017-06-14
• Last Update Posted: 2017-07-02

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 20

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

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	bortezomib	Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate	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

Name	Time	Method
Correlation of the Degree of Proteasome Inhibition in Peripheral Blood With the Degree of Proteasome Inhibition in Tumor Specimens	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.
Overall Survival	Up to 1 year	The time from initiation of therapy to death or last follow-up.
Time to Disease Progression	Up to 1 year	Time from initiation of therapy to first progressive disease.
Correlation of Phenotypic Expression of NF-kB, p53, and Other Molecular Markers in Biliary Washings and Tumor Biopsies With Clinical Outcomes	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	Duration of study treatment	Phenotypic expression of molecular markers before and after study treatment

Trial Locations

Locations (1)

Fox Chase Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States