PurIST Classification-Guided Adaptive Neoadjuvant Chemotherapy by RNA Expression Profiling of EUS Aspiration Samples

Inclusion Criteria (for Screening)

1. Have suspicion of pancreas adenocarcinoma and plan for endoscopic biopsy. Agrees toadditional EUS biopsy to be performed at the first-restaging timepoint and tissuecollection from surgical specimen.

2. Have a carbohydrate antigen 19-9 (CA19-9) level greater than 35 mg/dL regardless oftotal bilirubin level.

Inclusion Criteria (for Treatment)

1. Be 18 years of age or older.

2. Be able to understand and provide written informed consent or have a legallyauthorized representative (LAR).

3. Have documentation of histologically confirmed adenocarcinoma. Biopsy must have beencompleted prior to start of treatment Have an Eastern Cooperative Group (ECOG)performance status < 2 (please see the appendix).

4. Have documentation of histologically confirmed adenocarcinoma. Biopsy must have beencompleted prior to start of treatment.

5. Have clinical stage consistent with resectable or borderline resectableadenocarcinoma of the pancreas, based on CT or MRI findings.

6. Have adequate organ and bone marrow function, as defined by

• total leukocytes >3 x103/μL.

• absolute neutrophil count (ANC) >1.5x 103/μL.

• hemoglobin >9 g/dL.

• platelets >100 x 10e3/μL.

• creatinine clearance >60 mL/min or creatinine <1.5 mg/dL.

• bilirubin < 2 mg/dL.

• aspartate transaminases (AST/SGOT) and alanine transaminases (ALT/SGPT) <3 xupper limit of normal (ULN). At two weeks from biliary decompression, if thesubject's serum AST/ALT remains greater 3x ULN, but has demonstrated aprogressive decline, the subject may be enrolled into the trial and appropriatemodification and dose adjustments will be made to the assigned regimen.Eligibility of subjects whose AST/ALT remain elevated 3x ULN, withoutdemonstrating a downward trend, will be determined at the discretion of thetrial PIs.

7. Subjects must be CA19-9 producers as defined by a pretreatment CA 19-9 > 35 U/mL,when total bilirubin <2 mg/dL

8. Female patients must be postmenopausal (absence of menses for > 1 year), surgicallysterile or have a negative pregnancy test and use at least one form of contraceptionfor four weeks prior to Day 1 of the study, during study treatment and during thefirst four months after study treatment is discontinued. Male patients must besurgically sterile or use barrier contraception during the study and for four monthsafter the last dose of any study drug.

Exclusion Criteria:

1. Has received chemotherapy and/or radiation within three years prior to studyenrollment.

2. Has any previous history of another malignancy (other than cured basal or squamouscell carcinoma of the skin or cured in situ carcinoma of the cervix or localizedprostate cancer with normal prostate specific antigen) within three years of studyenrollment.

3. Uncontrolled comorbidities including, but not limited to, ongoing or active seriousinfection, symptomatic congestive heart failure, unstable angina, unstable cardiacarrhythmias, psychiatric illness, excessive obesity (BMI >55) or situations thatwould limit compliance with the study requirements or the ability to willingly givewritten informed consent.

4. Known HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

5. Pregnant or breastfeeding patients or any patient with childbearing potential notusing contraception four weeks prior to treatment.