The main research objective is to work out the optimal doses of the novel combination of gemcitabine, oxaliplatin and imatinib mesylate (glivec) in patients with advanced pancreatic cancer that has progressed during or after treatment with first-line gemcitabine.

Using the phase I study design, the dose of gemcitabine will be escalated in several steps to identify the highest tolerable dose that can be given safely. Based on pre-defined dose-limiting toxicity, the maximum tolerated dose of the combination will be identified and a safer dose for further evaluation of this regimen in pancreatic cancer selected. The primary objectives are therefore based around safety of the drug combination.

Inclusion Criteria:

• age > 18 years
• gemcitabine-refractory, histologically confirmed pancreatic cancer (progression during or within 6 months of first-line treatment)
• locally advanced or metastatic disease with measurable or non-measurable disease
• life expectancy of greater than 10 weeks
• prior treatment with investigational therapies including EGFR and VEGF antagonists is allowed when administered>4 weeks prior to start of therapy

Exclusion Criteria:

• any serious uncontrolled medical condition
• prior radiation treatment is not allowed
• no prior chemotherapy within the previous 4 weeks
• known peripheral neuropathy > CTCAE v 3.0 grade 1; absence of the deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible
• known brain metastases
• lack of physical integrity of the upper GI tract, malabsorption syndrome, or inability to take oral medication
• fertile women (<2 years after last menstruation) and men of childbearing potential not willing to use effective contraception
• pregnancy or breast feeding