Eryaspase and Modified FOLFIRINOX for the Treatment of Locally Advanced, Metastatic, or Unresectable Pancreatic Cancer

Inclusion Criteria

• Patient must be able to understand and willing to sign an Institutional Review Board (IRB) approved written informed consent document
• Patient must have histologically or cytologically confirmed pancreatic adenocarcinoma, which is locally advanced, unresectable, or metastatic
• Patient must have received no previous surgery, chemotherapy, radiotherapy or investigational therapy for the treatment of locally advanced or metastatic disease
• If a patient has had adjuvant/neoadjuvant therapy for localized disease, tumor recurrence or disease progression must have occurred no sooner than 6 months after completing the last dose of the aforementioned therapies
• Patient must have radiographically measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Patient must be > 18 years of age
• Patient must have a life expectancy of >= 3 months
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 1
• Absolute neutrophil count >= 1,500/mcl
• Platelets >= 100,000/mcl
• Hemoglobin >= 9.0 g/dL
• Serum Albumin >= 3.0 g/dL
• Creatinine should be below the upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal (using the Cockcroft-Gault formula)
• Plasma antithrombin III >= 70%
• Fibrinogen >= 150 mg/dL (1.5 g/L)
• International normalized ratio (INR) =< 1.5
• Partial thromboplastin time (PTT) =< institutional upper limit of normal (ULN)
• Total bilirubin =< 1.5 x institutional ULN
• Patients who have had a stent placed for biliary obstruction can be included in the study
• Female subject of childbearing potential must have a negative urine or serum pregnancy test
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately
• Male subjects with a female partner of childbearing potential must agree to use two adequate methods or a barrier method plus a method of contraception

Exclusion Criteria

• Patient must not have evidence of neuroendocrine tumor, duodenal adenocarcinoma, or ampullary adenocarcinoma
• Patient must not have a history of other malignancy =< 3 years ago, with the exception of basal cell or squamous cell carcinoma of the skin, which were treated with local resection only or carcinoma in situ of the cervix of ductal carcinoma in situ
• Patient must not be receiving any other investigational agents 28 days prior to the screening process
• Patient must not have brain metastases. Such patients must 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
• Patient must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to asparaginase, 5FU, oxaliplatin, or irinotecan
• Patient must not have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection , symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, any clinically active malabsorption syndrome, inflammatory bowel disease, any condition that increases the risk of severe irinotecan gastrointestinal toxicity, or psychiatric illness/social situations that would limit compliance with study requirements
• Has an active autoimmune disease, or a documented history of autoimmune disease or syndrome that requires steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule
• History of abdominal fistula, gastrointestinal perforation, peptic ulcer, or intraabdominal abscess within 6 months prior to randomization
• Has had an allogeneic tissue/solid organ transplant
• Has received or will receive a live vaccine within 30 days prior to the first administration of study medication. Seasonal flu vaccines that do not contain live virus are permitted
• Has known active hepatitis B or C
• Patient must not be pregnant and/or breastfeeding
• Patient must not be known to be human immunodeficiency virus (HIV)-positive on combination antiretroviral