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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase I/II Study of Gleevec (Imatinib Mesylate, Formerly Known as STI571) and Gemcitabine for Advanced Pancreas Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Gemcitabine
* Drug: Imatinib mesylate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|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.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine maximum tolerated dose according to toxicity |  | After 1 cycle of therapy (1 cycle = 21 days) | 
| Clinical response rate |  | After every 2 cycles of study therapy (1 cycle = 21 days) | 
| Overall survival at 6 months |  | After 6 months of study treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent pancreatic cancer, stage III pancreatic cancer, stage IV pancreatic cancer