The main purpose of this study is to see how pancrelipase affects the body mass index (BMI) in people with metastatic PDAC. BMI is a measure based on a person's height and weight. Other study goals are to explore two different dosing schedules of pancrelipase and to evaluate pancrelipase in people who do not have symptoms of EPI.

Inclusion Criteria:

• Histopathologic or cytologic diagnosis of pancreatic adenocarcinoma, or adenosquamous cancer, or any non-neuroendocrine primary pancreas variant, including acinar cancer.
• De novo or recurrent diagnosis of previously untreated stage IV PDAC with intent to receive FOLFIRINOX/mFOLFIRINOX.
• ECOG 0-2.
• No use of pancreatic enzyme replacement therapy within prior 2 weeks.
• Patients with biliary obstruction are eligible provided biliary stenting has or will occur before treatment with FOLFIRINOX.
• Ability to understand and the willingness to sign an informed consent document.
• Ability to swallow capsules.
• Age ≥18 years.
• Anticipated life expectancy of at least 6 months.

Exclusion Criteria:

• Chronic illness associated with malabsorption (celiac disease, cystic fibrosis, chronic pancreatitis, Crohn's disease).
• Fibrosing colonopathy.
• Prior history of surgical resection of the pancreas or gastric bypass.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Pancrelipase.
• Patients cannot receive radiation, IRE, or other localized therapy directed to the pancreas while on study.

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.