Dasatinib and Gemcitabine Hydrochloride or Gemcitabine Hydrochloride Alone in Treating Patients With Pancreatic Cancer Previously Treated With Surgery

PRIMARY OBJECTIVES: I. To compare disease-free survival at 18 months between
dasatinib-gemcitabine combination therapy and single-agent gemcitabine. SECONDARY OBJECTIVES:
I. To evaluate effects on disease-free survival of the dasatinib-gemcitabine combination
therapy compared with gemcitabine alone for adjuvant treatment of resected pancreatic
adenocarcinoma. II. To evaluate effects on overall survival of dasatinib-gemcitabine
combination therapy compared with gemcitabine alone for adjuvant treatment of resected
pancreatic adenocarcinoma. III. To evaluate tolerability and safety of the two arms. IV. To
identify potential biological correlates associated with clinical benefit to
dasatinib-gemcitabine combination therapy compared with gemcitabine alone. OUTLINE: Patients
are randomized to 1 of 2 treatment arms. ARM I: Patients receive gemcitabine hydrochloride IV
on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease
progression or unacceptable toxicity. ARM II: Patients receive gemcitabine hydrochloride IV
on days 1, 8, and 15 and oral dasatinib once daily on days 1-28. Treatment repeats every 28
days for 6 courses* in the absence of disease progression or unacceptable toxicity. NOTE: *
Courses with dasatinib repeat every 28 days for 1 year in the absence of disease progression
or unacceptable toxicity. After completion of study treatment, patients are followed up every
3 months for 2 years.

Inclusion Criteria:

- Written informed consent before beginning any protocol specified procedures

- Histologically proven pancreatic adenocarcinoma

- Any T, any N, M0 disease that has had all gross disease resected (R0 or R1 resection)

- ECOG Performance status index 0 or 1

- Absolute Neutrophils >= 1.5 x 10^9/L

- Platelets >= 100 x 10^9/L

- Hemoglobin >= 10 g/dL

- Total bilirubin =< 2.0 x UNL; subjects with Gilbert's syndrome, confirmed by
genotyping or invader UGTIA1 molecular assay before study entry must have total
bilirubin < 3 x UNL

- ASAT (SGOT) and ALAT (SGPT) =< 2.5 x UNL

- Alkaline Phosphatase =< 5 x UNL

- Creatinine < 1.5 x UNL

- Serum Na, K+, Magnesium, Phosphate and Calcium >= LNL

- First study treatment must be given within 60 days after surgery and within 7 days
after randomization

- Patients must be accessible for treatment and follow-up and compliant with study
procedures

- Negative pregnancy test (urine or serum) within 7 days before first study treatment
for all women of childbearing potential, whom also must implement adequate
non-hormonal contraceptive measures during study treatment and for at least 3 months
after the last dose of study therapy

- Ability to take oral medication (dasatinib must be swallowed whole)

Exclusion Criteria:

- Prior or concurrent systemic anticancer therapy (immunotherapy, hormonal therapy,
biological therapy, or chemotherapy) for pancreatic cancer

- Prior or concurrent radiation therapy for pancreatic cancer

- Pregnant or lactating patients

- M1 pancreatic cancer

- Concurrent congestive heart failure, unstable angina pectoris, or M1 within the 6
months before first study treatment

- Uncontrolled hypertension or high-risk uncontrolled arrhythmias

- Any history of clinically significant ventricular arrhythmias (such as ventricular
tachycardia, ventricular fibrillation, or torsades de pointes)

- Diagnosed or suspected congenital long QT syndrome

- Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec)

- History of significant neurologic or psychiatric disorders including psychotic
disorders, dementia or seizures that would prohibit the understanding and giving of
informed consent

- Past or current history of neoplasm other than pancreatic adenocarcinoma, except for:
curatively treated non-melanoma skin cancer; in situ carcinoma of the cervix; other
cancer curatively treated and with no evidences of disease for at least 1 year

- Concurrent treatment with other experimental drugs or treatment with investigational
drugs within 30 days of first study treatment

- Currently receiving drugs with known significant CYP 3A4 inhibitory effects (such as
ketoconazole, itraconazole, troleandomycin, erythromycin, diltiazem, verapamil,
ritonavir, indinavir)

- Concurrent administration with inducers of CYP 3A4 may result in a lower exposure to
dasatinib and are therefore not allowed (e.g., phenytoin, carbamazepine, rifampicin,
phenobarbital, pentobarbital, or St John's Wort)

- Known allergy reactions to dasatinib or gemcitabine or excipients used in the study

- History of significant bleeding disorders unrelated to cancer, including: diagnosed
congenital bleeding disorders (e.g., Von Willebrand's disease); diagnosed acquired
bleeding disorder within 1 year (e.g., acquired anti-factor VIII antibodies); ongoing
or recent (=< 3 months) significant gastrointestinal bleeding

- Patients currently taking drugs that are generally accepted to have a risk of causing
Torsades De Pointes including: quinidine, procainamide, disopyramide; amiodarone,
sotalol, ibutilide, dofetilide; erythromycins, clarithromycin; chlorpromazine,
haloperidol, mesoridazine, thioridazine, pimozide; cisapride, bepridil, droperidol,
methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine,
sparfloxacin, lidoflazine

- Concurrent treatment with intravenous bisphosphonates; prior treatment should be
stopped at least 2 weeks before first dose of study treatment

- Concurrent medical condition which may increase the risk of toxicity, including
pleural or pericardial effusion or any grade

- Active uncontrolled infection requiring parenteral antimicrobials