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


Phase 2
18 Years
N/A
Not Enrolling
Both
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

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Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Proportion of patients with complete or partial response, evaluated using the international criteria proposed by the RECIST Committee

Outcome Time Frame:

Up to 1 year

Safety Issue:

No

Principal Investigator

Steven Cohen

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fox Chase Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00046

NCT ID:

NCT00085410

Start Date:

January 2004

Completion Date:

Related Keywords:

  • 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
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Liver Neoplasms
  • Gallbladder Neoplasms
  • Bile Duct Neoplasms
  • Gastrointestinal Neoplasms

Name

Location

Fox Chase Cancer CenterPhiladelphia, Pennsylvania  19111