Inclusion Criteria:

- Histologically or cytologically confirmed pancreatic adenocarcinoma

- T1-3, N0-1, and M0 disease

- Surgically resectable disease confirmed by a surgeon experienced in pancreatic
surgery

- No borderline resectable disease defined as any of the following:

- Tumors with severe unilateral or bilateral SMV/portal involvement
impingement

- Abutment (or) encasement of hepatic artery

- SMA or celiac encasement (or) presence of SMV occlusion by tumor

- No metastatic disease

- ECOG performance status 0-1

- Life expectancy > 6 months

- WBC ≥ 3,000/mm³

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 9 g/dL

- Total bilirubin ≤ 2 mg/dL

- AST and ALT ≤ 2.5 times upper limit of normal

- Creatinine ≤ 2 mg/dL

- Calcium, magnesium, phosphorous, and potassium normal

- Negative pregnancy test

- Not pregnant or nursing

- Fertile patients must use effective barrier-method contraception 4 weeks before,
during, and for ≥ 12 months after completion of treatment

- Able to swallow tablets

- No malabsorption syndrome or other condition that would interfere with intestinal
absorption

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to gamma-secretase inhibitor RO4929097 or other agents used in
the study

- No uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, or
hypokalemia despite adequate electrolyte supplementation

- Grade 1 hyponatremia with sodium ≤ 131 mg/dL is permissible

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

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia other than chronic

- Stable atrial fibrillation

- Psychiatric illness/social situations that would limit compliance with study
requirements

- No baseline QTcF > 450 msec (male) or QTcF > 470 msec (female)

- Patients with a prior cancer with evidence of active cancer are excluded from this
study

- Patients with a prior cancer are permitted to enter this study as long as there
is no documented evidence of active malignancy

- No uncontrolled electrolyte abnormalities including hypocalcemia, hypomagnesemia, and
hypokalemia

- No symptomatic congestive heart failure, unstable angina pectoris, and a history of
torsades de pointes or other significant cardiac arrhythmias

- No requirement for antiarrhythmics or other medications known to prolong QTc

- No other concurrent anticancer agents or therapies

- Recovered to < grade 2 toxicity related to prior therapy

- No prior chemotherapy or radiotherapy for pancreatic cancer

- No other concurrent investigational agents

- No concurrent medications with narrow therapeutic indices that are metabolized by
cytochrome P450 (CYP450), including warfarin sodium (Coumadin®), ketoconazole, or
grapefruit juice

- No concurrent strong inducers or inhibitors of CYP3A4

- No concurrent combination antiretroviral therapy for HIV-positive patients