Phase II Study of Dasatinib (BMS-354825) in Patients With Metastatic Adenocarcinoma of the Pancreas

Inclusion Criteria:

- Histologically or cytologically confirmed adenocarcinoma of the pancreas

- Metastatic disease

- Measurable or evaluable/nonmeasurable disease

- No known brain metastases

- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

- Life expectancy > 12 weeks

- Absolute granulocyte count >= 1,500/mm^3

- Platelet count >= 100,000/mm^3

- Hemoglobin > 8.5 g/dL

- Bilirubin =< 1.5 times upper limit of normal (ULN)

- AST and ALT =< 2.5 times ULN

- Creatinine =< 2.0 mg/dL

- Not pregnant or nursing

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to dasatinib

- No QTc prolongation (i.e., QTc interval >= 480 msecs [Fridericia correction]) or
other significant ECG abnormalities

- LVEF normal by MUGA scan

- No condition that impairs ability to swallow and retain dasatinib tablets, including
any of the following:

- Gastrointestinal tract disease resulting in an inability to take oral medication
or a requirement for IV alimentation

- Prior surgical procedures affecting absorption

- Active peptic ulcer disease

- No clinically significant cardiovascular disease, including any of the following:

- Myocardial infarction or ventricular tachyarrhythmia within the past 6 months

- Major conduction abnormality (unless a cardiac pacemaker is present)

- Recovered from all prior therapy

- More than 4 weeks since prior adjuvant chemotherapy (6 weeks for nitrosoureas or
mitomycin C) and/or radiotherapy

- No prior chemotherapy for metastatic disease

- More than 4 weeks since prior EGFR inhibitors (e.g., imatinib mesylate, gefitinib,
erlotinib hydrochloride, or lapatinib ditosylate)

- No prior EGFR inhibitors that target Src kinases

- At least 7 days since prior and no concurrent agents with proarrhythmic potential

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent grapefruit or grapefruit juice

- No other concurrent anticancer agents or therapies

- No concurrent systemic antacids (i.e., H2-receptor antagonists and proton pump
inhibitors) [Locally acting antacids (e.g., Maalox, Mylanta) allowed within either 2
hours before or 2 hours after dasatinib therapy]

- No concurrent uncontrolled illness, including, but not limited to, any of the
following:

- Ongoing or active infection

- History of significant bleeding disorder, including congenital (von Willebrand's
disease) or acquired (anti-factor VIII antibodies) disorders

- Large pleural effusions

- Psychiatric illness or social situation that would preclude study compliance

- More than 7 days since prior and no concurrent CYP3A4 inducers or inhibitors

- No other concurrent investigational agents