• Radiographic Response [ Time Frame: Within 21 days of starting study drug ]
  Radiographic response to FOLFIRINOX and SBRT will be done by comparing IV contrast CT scans before and after therapy.
• Rates of Recurrence [ Time Frame: Up to 3 years ]
  Rates of recurrence (local only, systemic only, and both local and systemic) will be monitored for up to 3 years depending on time when the initiation of treatment begins.
• Rates of grade 3 or greater gastrointestinal toxicity [ Time Frame: Up to 3 months post treatment ]
  Grade 3 or greater gastrointestinal toxicities will be monitored including acute toxicities occurring within 3 months of treatment, and late toxicities occurring over 3 months after completion of radiation.
• Overall Survival [ Time Frame: Up to 3 years ]
  Patients will be monitored for overall survival for up to 3 years depending on time when the initiation of treatment begins.

The Primary and Secondary are listed below.

Primary Objective:

- To evaluate progression free survival after modified FOLFIRINOX and SBRT in borderline resectable and locally advanced pancreatic cancer.

Secondary Objective:

• To evaluate the radiographic response to FOLFIRINOX and SBRT by comparing IV contrast CT scans before and after therapy.
• To determine rates of recurrence (local only, systemic only, and both local and systemic), and overall survival.
• To determine rates of grade 3 or greater gastrointestinal toxicity, including acute toxicities occurring within 3 months of treatment, and late toxicities occurring over 3 months after completion of radiation.

• Drug: mFOLFIRINOX
  Patients will receive 6-12 cycles of mFOLFIRINOX every 2 weeks
• Radiation: Stereotactic body radiotherapy (SBRT)
  Stereotactic body radiotherapy (SBRT) will be delivered to the primary tumor and any adjacent involved lymph nodes to 33 Gy in 5 fractions over the course of 2 weeks, and within 4 weeks of chemotherapy.

Inclusion Criteria:

• Histologically confirmed pancreatic adenocarcinoma
• Borderline resectable pancreatic adenocarcinoma or locally advanced pancreatic adenocarcinoma
• No evidence of extrapancreatic disease on diagnostic imaging
• No evidence of invasion into the duodenum or stomach, as determined by EGD/EUS
• No prior treatment (chemotherapy, biological therapy, or radiotherapy) for pancreatic cancer
• No prior treatment with oxaliplatin, irinotecan, fluorouracil, or capecitabine
• ECOG Performance Status of 0-1
• No other malignancy within past five years (exceptions include basal cell carcinoma of the skin, cervical carcinoma in situ, and non-metastatic prostate cancer)
• No evidence of second malignancy at the time of study entry
• No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
• No > grade 2 sensory peripheral neuropathy
• No uncontrolled seizure disorder, active neurological disease, or known CNS disease
• No significant cardiac disease, including the following: unstable angina, New York Heart Association class II-IV congestive heart failure, myocardial infarction within six months prior to study enrollment
• Not pregnant and not nursing
• No other medical condition or reason that, in the opinion of the investigator, would preclude study participation

• Laboratory parameters as follows:

  • Absolute neutrophil count ≥1,500/uL,
  • Platelet count ≥75,000/uL,
  • Hemoglobin ≥9 g,/dL,
  • Creatinine <1.5 X ULN or estimated GFR >30 ml/min,
  • Bilirubin <1.5 X ULN,
  • AST and ALT <3 X ULN,
  • Negative pregnancy test in women of childbearing potential
• Able to be treated with SBRT only at the Smilow New Haven campus
• Able to have fiducials placed in the pancreas

Exclusion Criteria:

• Failing to meet any of the Inclusion Criteria