Study is being abandoned.

The purpose of this study is to research the effects of delivering full-dose neoadjuvant multi-agent chemotherapy (folfirinox) followed by stereotactic body radiation therapy (SBRT) in patients with resectable pancreatic ductal adenocarcinoma (PDAC) in order to intensify local therapy and improve outcomes.

Primary Objectives:

1. To assess one-year local control rates in patients with operable PDAC who receive neoadjuvant chemotherapy and SBRT

Secondary Objectives:

1. To assess the following disease control endpoints: pathological response, disease-free survival, overall survival, failure pattern (local vs. distant) and time to development of distant metastases
2. To assess safety of the SBRT regimen

Exploratory objectives

1. To obtain exploratory data correlating tumor response grade with changes in circulating tumor DNA levels following chemotherapy, SBRT, and surgery in patients with PDAC
2. To obtain exploratory data correlating circulating tumor DNA (ctDNA) changes with disease control endpoints (overall survival, disease-free survival, failure pattern, and time to development of distant metastases)
3. To obtain exploratory data on positron emission tomography (PET) and magnetic resonance imaging (MRI) findings and correlations with tumor response among patients treated on study.

Inclusion Criteria:

1. Age ≥ 18 years

2. Pathologic confirmation of pancreatic ductal adenocarcinoma

3. Resectable disease (determined by treating surgeon)

4. Patients planning to receive neoadjuvant Folfirinox as part of their standard of care treatment

5. No evidence of distant organ metastatic disease

6. Eastern Cooperative Oncology Group Performance status 0-1

7. Ability to understand and the willingness to sign informed consent document

8. Adequate organ function, defined by the following laboratory values, at the time of study entry:

   1. Hemoglobin ≥ 10 g/dL (transfusions acceptable)
   2. Absolute Neutrophil Count ≥ 0.5 x 109/L
   3. Platelets ≥ 100 x 109/L
   4. Creatinine ≤ 1.5x institutional upper limit of normal (ULN) or creatinine clearance ≥ 50 mL/min
   5. Total bilirubin ≤ 2x institutional ULN
   6. Aspartate aminotransferase test (AST)/ Alanine Aminotransferase Test (ALT) ≤ 3x institutional ULD

Exclusion Criteria:

1. Severe/uncontrolled intercurrent illness that, in the opinion of the patient's treating physicians, would prevent the patient from receiving either multi agent chemotherapy, high-dose radiation, or undergoing resection of the pancreatic tumor
2. Prior therapy for PDAC
3. Prior radiation to the upper abdomen (RT to other sites acceptable)
4. Inability to undergo port or PICC line placement
5. Active gastric or duodenal ulcer
6. Tumor invasion of the intestinal or gastric lumen
7. Active hepatitis B or other active serious infections
8. Pregnant and breastfeeding women are excluded. Women of child-bearing potential must have a negative urine or serum pregnancy test and be willing to use acceptable methods of birth control (hormonal or barrier method of birth control; abstinence) to avoid pregnancy for the duration of the study treatment
9. Life expectancy of < 3 months
10. Patients with contraindications to either PET scan or MRI (e.g., pacemaker/ICD) will NOT be excluded from study participation. Such patients will be treated per protocol but will not be required to undergo PET-MRI.