Imatinib Mesylate and Gemcitabine in Treating Patients With Locally Advanced, Metastatic, or Recurrent Pancreatic Cancer

This study has been terminated.
(Closed to accrual to allow enrollment on another more promising trial.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Northwestern University
ClinicalTrials.gov Identifier:
NCT00281996
First received: January 24, 2006
Last updated: August 24, 2011
Last verified: August 2011
  Purpose

RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving imatinib mesylate together with gemcitabine may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of giving imatinib mesylate together with gemcitabine and to see how well they work in treating patients with locally advanced, metastatic, or recurrent pancreatic cancer.


Condition Intervention Phase
Pancreatic Cancer
Drug: Gemcitabine
Drug: Imatinib mesylate
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Gleevec (Imatinib Mesylate, Formerly Known as STI571) and Gemcitabine for Advanced Pancreas Cancer

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Determine maximum tolerated dose according to toxicity [ Time Frame: After 1 cycle of therapy (1 cycle = 21 days) ] [ Designated as safety issue: Yes ]
  • Clinical response rate [ Time Frame: After every 2 cycles of study therapy (1 cycle = 21 days) ] [ Designated as safety issue: No ]
  • Overall survival at 6 months [ Time Frame: After 6 months of study treatment ] [ Designated as safety issue: No ]

Enrollment: 19
Study Start Date: March 2005
Study Completion Date: October 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Gemcitabine
    Administered intravenously over 30 minutes on days 1 and 8 of a 21-day cycle starting at a dose of 700 mg/m2 and increasing to 1000mg/m2 by cohorts
    Drug: Imatinib mesylate
    Administered orally once daily with 8 ounces of water at a starting dose of 300 mg/day and increased to 600 mg/day according to cohort.
    Other Name: Gleevec
Detailed Description:

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose of imatinib mesylate and gemcitabine hydrochloride in patients with locally advanced, metastatic, or recurrent pancreatic cancer.
  • Determine the clinical response rate in patients treated with this regimen.
  • Determine the 6-month and overall survival of patients treated with this regimen.

Secondary

  • Determine the toxicity profile of this regimen in these patients.
  • Correlate response with expression of platelet-derived growth factor (PDGF) and PDGF receptor in tumor tissue from patients treated with this regimen.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

  • Phase I: Patients receive oral imatinib mesylate once daily on days 1-14 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8*. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-5 patients receive escalating doses of imatinib mesylate and gemcitabine hydrochloride until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 5 or 3 of 5 patients experience dose-limiting toxicity.

NOTE: *The first cohort receives gemcitabine hydrochloride on days 1, 8, and 15

  • Phase II: Patients receive imatinib mesylate and gemcitabine hydrochloride at the MTD determined in phase I in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed pancreatic cancer

    • Locally advanced, metastatic, or recurrent disease
  • Measurable or evaluable disease by physical exam, plain radiographs, CT scan, or MRI
  • No brain metastases

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy of 12 weeks or greater
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST ≤ 2.5 times ULN (5 times ULN if liver metastases are present)
  • No chronic liver disease (i.e., chronic active hepatitis or cirrhosis)
  • Creatinine ≤ 2.0 mg/dL
  • No chronic renal disease
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier-method contraception during and for ≥ 3 months after completion of study treatment
  • No other malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix
  • No uncontrolled diabetes
  • No active uncontrolled infection
  • No other severe and/or uncontrolled medical disease
  • HIV negative

PRIOR CONCURRENT THERAPY:

  • No prior therapy for metastatic disease

    • Prior fluorouracil as a radiosensitizer for adjuvant therapy after surgery or for locally advanced disease is permitted if local disease has recurred or progressed ≥ 3 months after completion of therapy or disease is present outside the radiation field
  • At least 2 weeks since prior major surgery
  • No concurrent grapefruit or grapefruit juice
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00281996

Locations
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
Investigators
Principal Investigator: Mary Mulcahy, MD Robert H. Lurie Cancer Center
  More Information

No publications provided

Responsible Party: Northwestern University
ClinicalTrials.gov Identifier: NCT00281996     History of Changes
Other Study ID Numbers: NU 02I8, NU-02I8, NU-0948-003
Study First Received: January 24, 2006
Last Updated: August 24, 2011
Health Authority: United States: Federal Government

Keywords provided by Northwestern University:
recurrent pancreatic cancer
stage III pancreatic cancer
stage IV pancreatic cancer

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Imatinib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014