Study of Irinotecan,Oxaliplatin, and S1 in Patients With Advanced Pancreatic Cancer

Inclusion Criteria:

* • Cytologically- or histologically-confirmed pancreatic adenocarcinoma or poorly differentiated pancreatic carcinoma that is metastatic to distant sites.

  * Other histologies such as neuroendocrine and acinar cell carcinoma are excluded.
  * No prior chemotherapy for locally advanced or metastatic pancreatic cancer.
  * Patients are eligible if they received adjuvant treatment after surgical resection
  * Participants are required to have measurable disease (RECIST v1.1), defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \> 20 mm with conventional techniques or as \> 10 mm with spiral CT scan. See section 11 for the evaluation of measurable disease.
  * Participants enrolled must have disease that is accessible for tumor biopsies and must agree to a pre-treatment tumor biopsy.
  * Age ≥ 18 years. Because no dosing or adverse event data are currently available in participants \<18 years of age, children are excluded from this study but will be eligible for future pediatric trials.
  * ECOG performance status ≤2 (see Appendix A)
  * Patients must have completed any major surgery or open biopsy ≥4 weeks from start of treatment.
  * Participants must have adequate organ and marrow function as defined below:

    * Absolute neutrophil count ≥1,500/mcL
    * Platelets ≥100,000/mcL
    * Total bilirubin ≤1.5 × institutional upper limit of normal
    * AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
    * Creatinine ≤1.5 × institutional upper limit of normal OR
    * Creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above 1.5 × upper limit of normal.
  * Negative serum pregnancy test for women of childbearing potential.
  * Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* • Prior chemotherapy or any other investigational agents for the treatment of locally advanced or metastatic pancreatic cancer

  * Concurrent use of any other anti-cancer therapy, including chemotherapy, targeted therapy, immunotherapy, or biological agents.
  * Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Screening for brain metastases with head imaging is not required.
  * History of allergic reactions attributed to compounds of similar chemical or biologic composition to above drugs or other agents used in study.
  * History of prior or current synchronous malignancy, except:

    o Malignancy that was treated with curative intent and for which there has been no known active disease for \>3 years prior to enrollment
  * Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, NYHA class III/IV congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.