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

NCT00085410 | Terminated Phase 2 Results

• 4 other identifiers: NCI-2009-00046CDR000036971503-0426135
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  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 Outcomes (5)

• Time to Disease Progression

  Up to 1 year

• Overall Survival

  Up to 1 year

• 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)

• 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)

• Correlation of Treatment With Changes in Phenotypic Expression of Molecular Markers

  Duration of study treatment

Study Arms (1)

Arm I

EXPERIMENTAL

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

Drug: bortezomib

Interventions

bortezomib DRUG

Given IV

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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) \[Note: Biliary shunting or stenting allowed to achieve the required bilirubin and transaminase levels\]

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111-2497, United States

Location

Related Publications (1)

• 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.

  PMID: 24512954 RESULT

MeSH Terms

Conditions

Gastrointestinal Neoplasms; Carcinoma, Hepatocellular; Bile Duct Neoplasms; Gallbladder Neoplasms

Interventions

Bortezomib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Liver Diseases; Biliary Tract Neoplasms; Bile Duct Diseases; Biliary Tract Diseases; Gallbladder Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

The trial was discontinued early due to no confirmed partial responses.

Results Point of Contact

• Title: Assistant Professor, Medical Oncology
• Organization: Fox Chase Cancer Center

crystal.denlinger@fccc.edu

215-214-1676

Study Officials

• Steven Cohen

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2004
• First Posted: June 11, 2004
• Study Start: January 1, 2004
• Primary Completion: August 1, 2008
• Study Completion: April 1, 2010
• Last Updated: July 2, 2017
• Results First Posted: June 14, 2017

Record last verified: 2017-06

Locations

US (1)