Gemcitabine and Imatinib Mesylate as First-Line Therapy in Patients With Locally Adv. or Metastatic Pancreatic Cancer

Study Overview
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Brief Summary
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RATIONALE: 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. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine together with imatinib mesylate may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving gemcitabine together with imatinib mesylate works as first-line therapy in treating patients with locally advanced or metastatic pancreatic cancer.

Detailed Description
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OBJECTIVES: Primary Evaluate the time to progression in patients with locally advanced or metastatic pancreatic cancer treated with gemcitabine hydrochloride and imatinib mesylate as first-line therapy. Secondary Assess the response rate in patients treated with this regimen. Assess the percentage of patients treated with this regimen who survive 1 year or more. Assess the toxicity of this regimen in these patients. Assess the overall survival of patients treated with this regimen. OUTLINE: This is a multicenter, nonrandomized, open-label, uncontrolled study. Patients receive gemcitabine hydrochloride IV over 120 minutes on days 3 and 10 and oral imatinib mesylate on days 1-5 and 8-12. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months. PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.

Official Title
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Phase II Study of Imatinib Mesylate and Gemcitabine for First-line Treatment of Metastatic Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: gemcitabine hydrochloride
* Drug: imatinib mesylate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed pancreatic adenocarcinoma or poorly differentiated carcinoma (originating in the pancreas) Locally advanced or metastatic disease Not eligible for curative resection Must have measurable or evaluable disease as defined by RECIST criteria No CA19-9 elevation as only evidence of disease No known brain metastases PATIENT CHARACTERISTICS: ECOG performance status 0-2 Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 125,000/mm³ Bilirubin < 1.5 times upper limit of normal (ULN) AST and ALT ≤ 2.5 times ULN Alkaline phosphatase < 3 times ULN Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective nonhormonal contraception No coexisting medical condition that would preclude study compliance No inability to ingest tablets No active illness (e.g., active or uncontrolled infection, uncontrolled cardiac disease) that would preclude study participation No chronic uncontrolled diarrhea and/or daily emesis No other cancer within the past 5 years except for surgically removed noninvasive nonmelanoma skin cancer or in situ cervical cancer PRIOR CONCURRENT THERAPY: No prior chemotherapy for metastatic disease No prior gemcitabine No prior imatinib mesylate Prior surgical resection and adjuvant fluorouracil chemotherapy allowed provided there was an interval of > 6 months between the last dose of adjuvant chemotherapy and recurrence of pancreatic cancer Prior fluorouracil as a radiosensitizing agent allowed At least 4 weeks since prior radiotherapy and recovered Must have evidence of disease outside the radiation fields OR radiologically confirmed disease progression within the radiation fields after completion of radiotherapy No concurrent therapeutic warfarin Prophylactic warfarin ≤ 1 mg daily allowed for prophylaxis of central venous catheter thrombosis Low molecular weight heparin or heparin allowed for anticoagulation No concurrent chronic systemic corticosteroids No other concurrent agents or therapies, including chemotherapy, immunotherapy, hormonal cancer therapy, radiotherapy, or cancer surgery No other concurrent experimental medications No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gemcitabine and Imatinib<br> | Drug: gemcitabine hydrochloride<br> <br> Drug: imatinib mesylate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression-free survival in months. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | Response rate as defined by a best response of Stable Disease or better. | 5 years | 
| 1-year Survival Rate | Percentage of subjects who survive up to 1 year | 5 years | 
| Overall Survival |  | 5 years | 

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