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