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

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.

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)