PRIMARY OBJECTIVES:

      I. To evaluate and estimate 18 months overall survival (OS) rate of patients with borderline
      resectable pancreatic ductal adenocarcinoma (PDAC) receiving neoadjuvant therapy.

      SECONDARY OBJECTIVES:

      I. To evaluate and estimate the R0 resection rates in patients receiving each of the two
      multimodality treatment regimens.

      II. To evaluate and estimate the event-free survival in patients receiving each of the two
      multimodality treatment regimens.

      III. To evaluate and estimate the pathologic compete response (pCR) rates in patients
      receiving each of the two multimodality treatment regimens.

      IV. To assess the adverse events (AE) profile and safety of each treatment arm.

      TERTIARY OBJECTIVES:

      I. To test the effect of the rs2853564 vitamin D receptor (VDR) variant on OS rate and
      discover novel candidate genes associated with OS and severe toxicity of chemotherapy by
      using genome-wide genotyping approaches.

      II. To evaluate risk classification previously developed by Koay et al using normalized area
      under the enhancement curve (NAUC).

      III. To access prognostic value of NAUC ratio defined as post-neoadjuvant NAUC divided by
      pre-neoadjuvant therapy NAUC.

      IV. To evaluate risk classification previously developed by Koay et al using delta measure.

      OUTLINE: Patients are randomized to 1 of 2 treatment arms.

      ARM A: Patients receive oxaliplatin intravenously (IV) over 2 hours, irinotecan IV over 90
      minutes, and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil
      IV continuously over 46-48 hours on days 1-2. Treatment repeats every 14 days for 8 courses
      in the absence of disease progression or unacceptable toxicity.

      ARM B: Patients receive oxaliplatin intravenously (IV) over 2 hours, irinotecan IV over 90
      minutes, and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil
      IV continuously over 46-48 hours on days 1-2. Treatment repeats every 14 days for 7 courses
      in the absence of disease progression or unacceptable toxicity. Patients receive either
      stereotactic body radiation therapy (SBRT) or hypofractionated image guided radiation therapy
      (HIGRT) on days 1-5 of course 8.

      SURGERY Within 4 to 8 weeks after the last dose of chemotherapy (arm A) or of radiation (arm
      B), patients considered surgical candidates for resection (after central review) will undergo
      surgery at the registering institution.

      ADJUVANT CHEMOTHERAPY Within 4-12 weeks from the date of surgery, patients will receive
      oxaliplatin IV over 2 hours and leucovorin IV over 2 hours on day 1. Patients also receive
      fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 14 days
      for 4 courses in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 16 weeks for 2 years,
      then every 6 months for 5 years.