Liposomal Irinotecan in Combination With Oxaliplatin, Leucovorin, and 5-fluorouracil for Patients With Locally Advanced Pancreatic Carcinoma:

Inclusion Criteria:

* Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
* Age ≥ 18 years at the time of consent.
* ECOG Performance Status of 0-1 within 28 days prior to registration.
* Histological or cytological confirmation of pancreatic carcinoma.
* Measurable disease according to RECIST v1.1 within 28 days prior to registration.
* Previously untreated pancreatic carcinoma considered as locally advanced unresectable according to NCCN guidelines.
* Demonstrate adequate organ function as defined in the table below; All screening labs to be obtained within 14 days prior to initiation of study treatment.

  * Hematological

    * Absolute Neutrophil Count (ANC): \>/=1500/uL
    * Hemoglobin (Hgb): \>/=8 g/dL with blood transfusion permitted
    * Platelet (Plt): \>/=100,000/uL
  * Renal

    * Serum creatinine: \</=1.5 x upper limit of normal (ULN) OR
    * Calculated creatinine clearance using the Cockcroft-Gualt formula: \>/=50 mL/min for subjects with creatinine levels \>1.5 ULN
  * Hepatic

    * Total bilirubin: \</=1.5 x ULN (biliary drainage is allowed for biliary obstruction). Patients with Gilbert's syndrome with a total bilirubin \</=3.0 x ULN and direct bilirubin within normal limits are permitted
    * Aspartate aminotransferase (AST): \</=2.5 x ULN
    * Alanine aminotransferase (ALT): \</=2.5 x ULN
    * Albumin: \>/=3.0 g/dL
  * Coagulation ---International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT): \</=1.5 x ULN unless subject is receiving anticoagulant therapy, as long as PT, INR or PTT is within therapeutic range of intended use of anticoagulants
* Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days of study registration and within 72 hours of Cycle 1 Day 1. NOTE: Female subjects are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
* Female subjects of childbearing potential and males must be willing to abstain from behaviors that could lead to pregnancy (heterosexual activity, sperm donation, in vitro fertilization, etc.) or to use 2 forms of effective methods of contraception from the time of informed consent until 9 months (females) or 6 months (males) after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method.
* As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study. The subject should be able to understand the purpose and risks of the study and provide a signed and dated informed consent form.

Exclusion Criteria:

* Known hypersensitivity to irinotecan liposome, other liposomal products, oxaliplatin, 5-fluorouracil, leucovorin, or any ingredients in those preparations.
* Pre-existing peripheral neuropathy (Grade 3 or 4) during screening.
* Major surgery within 4 weeks of starting treatment.
* Active uncontrolled cardiac arrhythmia or congestive heart failure (class 3 or 4 as defined by the New York Heart Association Functional Classification); or history of myocardial infarction, unstable angina; or acute coronary syndrome within 6 months prior to enrollment.
* Known history of human immunodeficiency virus (HIV), or hepatic cirrhosis caused by active infection with hepatitis B virus (HBV, as defined by HBsAg positivity or positive DNA). Testing is not required for study entry if there is no clinical suspicion. Note: hepatic cirrhosis caused by other factors (ex. alcoholic cirrhosis) may be considered on a case-by-case basis if, in the opinion of the treating investigator, the disease is unlikely to compromise the subject's safety or put the study outcomes at unnecessary risk.
* Any medical condition, life-threatening illness, or organ dysfunction, which in the investigator's opinion, can compromise the subject's safety or put the study outcomes at unnecessary risk.
* Uncontrolled active systemic infection.
* Concomitant medications that are prohibited in this study and they cannot be switched to alternative medications.
* Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
* Known additional malignancy that is active and/or progressive requiring treatment within 2 years of screening for this study; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, low-grade prostate cancer, or other cancer for which the subject has been disease-free for at least five years. Additional exceptions could be considered if agreed by sponsor-investigator and site investigator assuming the disease is considered extremely unlikely to confound evaluation of disease status.
* Treatment with any investigational drug within 30 days prior to registration, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior to the first scheduled day of dosing of this study.