Clinical trial NCT00085410: Bortezomib in Treating Patients With Unresectable Locally Advanced or Metastatic Adenocarcinoma of the Bile Duct or Gallbladder
Official title: Phase II and Pharmacodynamic Study of PS-341 in Patients With Unresectable or Metastatic Adenocarcinoma of the Bile Duct or Gallbladder
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-06-11
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Objective Response Rate
timeFrame: Up to 1 year
Secondary outcomes:
measure: Time to Disease Progression
timeFrame: Up to 1 year
measure: Overall Survival
timeFrame: Up to 1 year
measure: Correlation of the Degree of Proteasome Inhibition in Peripheral Blood With the Degree of Proteasome Inhibition in Tumor Specimens
timeFrame: Once in the screening period (within 14 days of starting treatment)
measure: Correlation of Phenotypic Expression of NF-kB, p53, and Other Molecular Markers in Biliary Washings and Tumor Biopsies With Clinical Outcomes
timeFrame: Once in the screening period (within 14 days of starting treatment)
measure: Correlation of Treatment With Changes in Phenotypic Expression of Molecular Markers
timeFrame: Duration of study treatment
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
Study officials:
affiliation: Fox Chase Cancer Center
name: Steven Cohen
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.