Inclusion Criteria:

- Histologically or cytologically confirmed adenocarcinoma of the pancreas (ductal or
undifferentiated); Note: If primary previously biopsied, tissue for diagnosis from
metastasis is not required and clinical staging is permitted

- Metastatic pancreatic cancer with metastases amenable to biopsy

- Measurable disease; NOTE: For patients having lesions measuring at least 1 cm to less
than 2 cm must use spiral computed tomography (CT) imaging for both pre- and
post-treatment tumor assessments

- Willingness to provide tissue and blood samples for research purposes

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

- Absolute neutrophil count (ANC) >= 1500 cell/uL

- Platelet (PLT) >= 100,000 cells/uL

- Total bilirubin < 1.5 x upper normal limit (UNL) (patients may be stented)

- Serum glutamic oxaloacetic transaminase (SGOT)(aspartate aminotransferase [AST]) =< 3
x UNL

- Creatinine < 1.5 x UNL

- Negative serum pregnancy test done =< 7 days prior to registration, for women of
childbearing potential only

- Life expectancy > 12 weeks

- Provide informed written consent

- Willing to return to Mayo Clinic enrolling institution for follow-up

- Agrees to use a reliable method of birth control, as determined by the patient and
his or her health-care team, during the study and for 3 months following the last
dose of study treatment; NOTE: This applies to both male and female patients of
reproductive potential

Exclusion Criteria:

- History of islet cell, acinar cell, or cystadenocarcinomas

- Prior cytotoxic chemotherapy for metastatic disease; exceptions:

- For Cohort I, prior leucovorin calcium, fluorouracil, irinotecan hydrochloride,
and oxaliplatin (FOLFIRINOX) is allowed

- For Cohort II, prior gemcitabine is allowed

- Any of the following prior treatments:

- Prior adjuvant chemotherapy for completely resected disease or chemoradiotherapy
for locally advanced disease =< 180 days prior to registration; Note:
Treatment-related toxicities must be resolved

- Gemcitabine or 5-fluorouracil used as either a radiosensitizer or as maintenance
therapy =< 180 days prior to registration; Note: Treatment-related toxicities
must be resolved

- Radiation therapy < 28 days prior to registration

- Immunotherapy < 28 days prior to registration

- Biologic therapy < 28 days prior to study registration

- Major surgery =< 28 days prior to registration

- Any of the following because this study involves an investigational agent whose
genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are
unknown:

- Pregnant women

- Nursing women

- Men or women of childbearing potential who are unwilling to employ adequate
contraception

- Co-morbid systemic illnesses or other severe concurrent disease which, in the
judgment of the investigator, would make the patient inappropriate for entry into
this study or interfere significantly with the proper assessment of safety and
toxicity of the prescribed regimens

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, or psychiatric illness/social situations that would limit compliance with
study requirements

- Cardiac issues consisting of either symptomatic congestive heart failure (New York
Heart Association class II or higher) unstable angina pectoris, and/or myocardial
infarction =<180 days prior to registration; cardiac arrhythmia (which is symptomatic
or requires treatment) including the following cardiac conduction abnormalities: QTc
prolongation > 450 msec on screening electrocardiogram (ECG), congenital long-
QT-syndrome, or left bundle branch block (LBBB), previous history of QTc prolongation
with another medication that required discontinuation or any concomitant medication
that may cause QTc prolongation, or induce Torsades de Pointes

- Systolic blood pressure >= 140 mm Hg, and diastolic blood pressure >= 90 mm Hg that
is not controlled by medical therapy

- Immunocompromised patients (other than that related to the use of corticosteroids)
including patients receiving HAART (highly active anti-retroviral therapy) treatment

- Currently receiving any other investigational agent which would be considered as
treatment for cancer

- Receiving treatment with an experimental agent for non-cancer indications that has
not received regulatory approval for any indication =< 28 days prior to study entry