Comparing Two Treatment Combinations, Gemcitabine and Nab-Paclitaxel With 5-Fluorouracil, Leucovorin, and Liposomal Irinotecan for Older Patients With Pancreatic Cancer That Has Spread

Inclusion Criteria:

   - Newly diagnosed untreated metastatic adenocarcinoma of the pancreas. However, previous
   surgery, adjuvant chemotherapy and/or radiation therapy will be allowed, provided
   radiation therapy is completed at least 2 weeks prior to registration and adjuvant
   therapy was administered more than 6 months prior to registration. Patients with the
   following histology are excluded: acinar cell; adenosquamous carcinoma

   - Eastern Cooperative Oncology Group (ECOG) performance status 0-2

   - Patient is an English speaker with the ability to understand and complete the informed
   consent and questionnaires

   - Leukocytes >= 3,000/mcL (obtained within 4 weeks of registration)

   - Absolute neutrophil count >= 1,500/mcL (obtained within 4 weeks of registration)

   - Platelets >= 100,000/mcL (obtained within 4 weeks of registration)

   - Total bilirubin =< institutional upper limit of normal (ULN) (obtained within 4 weeks
   of registration)

   - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
   [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
   =< 2.5 x institutional ULN (obtained within 4 weeks of registration)

   - Creatinine =< institutional ULN unless data exists supporting safe use at lower kidney
   function values, no lower than 30 mL/min/1.73 m^2 (obtained within 4 weeks of
   registration)

   - Glomerular filtration rate (GFR) >= 40 mL/min/1.73 m^2 unless data exists supporting
   safe use at lower kidney function values, no lower than 30 mL/min/1.73 m^2 (obtained
   within 4 weeks of registration)

   - Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
   therapy with undetectable viral load within 6 months of registration are eligible for
   this protocol. HIV positive (+) patients who are on ritonavir or/and cobicistat-based
   regimen must be switched to alternative anti-retroviral therapy (ART)

   - For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
   load must be undetectable on suppressive therapy, if indicated

   - Patients with a history of hepatitis C virus (HCV) infection must have been treated
   and cured. For patients with HCV infection who are currently on treatment, they are
   eligible if they have an undetectable HCV viral load

   - Male patients must agree not to father children while on study

   - Patients with known history or current symptoms of cardiac disease, or history of
   treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
   function using the New York Heart Association functional classification. To be
   eligible for this protocol, patients should be class 2B or better

   - Patients must have measurable disease and scans must be done within 4 weeks of
   registration

   - Patients classified to have mild-moderate abnormalities in any of the domains
   evaluated in the screening geriatric assessment and are classified as "vulnerable" are
   eligible. Patients classified without any abnormalities ("fit") or with severe
   cognitive/functional impairment or high co-morbidity score ("frail") on the screening
   geriatric assessment are ineligible

   - Patients must agree not to take any medications or substances that are strong
   inhibitors or inducers of CYP3A4. Those who are randomized to liposomal irinotecan
   treatment arm should avoid drugs that are UGT1A1 inhibitors