In this clinical trial, if the doctor knows or suspects that a growth in the pancreas is cancer (adenocarcinoma), then a sample of the growth is tested (the test is called molecular profiling). The results of the test are used by the doctor to recommend therapy (chemotherapy and radiation therapy) that the patient will receive before having surgery to remove the adenocarcinoma. When the patient goes to surgery, the adenocarcinoma that is removed is tested again. The results of that test are used to guide the choice of therapy after surgery.

The chemotherapy drugs and the radiation therapy used in this clinical trial are already approved for treatment of pancreas cancer. This trial is intended to establish which treatment is best for a specific patient, based on test results from that patient's actual adenocarcinoma. In the past, the decision as to which treatment the patient will receive was not based on testing of the actual adenocarcinoma.

See treatment pathways at http://www.mcw.edu/surgery/patientinfo/Pancreatic-Cancer-Trial.htm.

Hypothesis: Resectability rate, overall survival rate and progression-free survival in subjects with adenocarcinoma of the pancreas will be superior for who receive targeted "personalized" therapy.

Inclusion criteria:

• 18 years of age or older
• Able to understand and provide written informed consent
• Diagnosis of adenocarcinoma of the pancreas or high suspicion of adenocarcinoma of the pancreas based on CT and MRI findings as detailed below by "Definition of...."

Treatment Eligibility Criteria:

• Have an Eastern Cooperative Oncology Group performance status less than or equal to 2

• Have biopsy-proven resectable or borderline resectable adenocarcinoma of the pancreas

• Have adequate organ and bone marrow function as defined by:

  • total leukocytes greater than or equal to 3 x1000/μL
  • absolute neutrophil count (ANC) > or equal to 1.5x 1000/μL
  • hemoglobin > or equal to 9 g/dL
  • platelets > or equal to 100 x 1000/μL
  • creatinine clearance >60 mL/min or creatinine < or equal to 1.5 mg/dL
  • bilirubin < or equal to 2 mg/dL or >2 and declining as described in the protocol
  • aspartate transaminases (AST/SGOT) < or equal to3 x upper limit of normal (ULN)
  • alanine transaminases (ALT/SGPT) < or equal to 3 x ULN

• Female patients must be post menopausal for > 1 year, surgically sterile, or have a negative pregnancy test and used at least one form of contraception for 4 weeks prior to Day 1 of the study, during study treatment and during the first 4 months after study treatment is discontinued. Male patients must be surgically sterile or use barrier contraception during the study and for 4 months after the last dose of any study drug.

Definition of Resectable Pancreatic Cancer includes:

• No evidence of extra-pancreatic disease
• No evidence of tumor-arterial abutment (celiac, superior mesenteric artery or hepatic artery)
• If tumor induced narrowing of the superior mesenteric vein, portal vein or superior mesenteric-portal vein confluence is present it must be <50% of the diameter of the vessel
• Ca19-9 <5000, when bilirubin is <2 (or >2 and declining as described in the protocol)

Definition of Borderline Resectable Pancreatic Cancer to include at least one of the following:

• Tumor abutment < or equal to 180 degrees of the superior mesenteric artery or celiac axis
• Tumor abutment or encasement (>180 degrees) of a short segment of the hepatic artery
• Tumor induced narrowing of superior mesenteric vein, portal vein or superior mesenteric-portal vein of >50% of the diameter of the vessel.
• Short segment occlusion of the superior mesenteric vein, portal vein or superior mesenteric-portal vein confluence with a suitable portal vein above and superior mesenteric vein below, for reconstruction
• CT or MRI findings suspicious for, but not diagnostic of, metastatic disease (based on multidisciplinary assessment at the Medical College of Wisconsin weekly pancreatic cancer conference)
• Biopsy proven N1 disease (regional lymph nodes involved) from pre-referral biopsy or endoscopic ultrasound-guided fine needle aspirate
• Resectable tumor and cancer antigen 19-9 (CA19-9) >5000

Exclusion Criteria:

Any patient with one or more of the following will be excluded:

• Have received chemotherapy or chemoradiation within 5 years prior of study enrollment
• Have any previous history of another malignancy (other than cured basal or squamous cell carcinoma of the skin or cured in-situ carcinoma of the cervix) within 5 years of study enrollment
• Uncontrolled comorbidities including, but not limited to, ongoing or active serious infection, symptomatic congestive heart failure, unstable angina, unstable cardiac arrhythmias, psychiatric illness, excessive obesity, or situations that would limit compliance with the study requirements or the ability to willingly give written informed consent
• Known human immunodeficiency virus, hepatitis B virus, or hepatitis C virus infection
• Pregnant or breast-feeding patients or any patient with child-bearing potential not using contraception 4 weeks prior to, during and 4 months after study treatment is discontinued