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

PRIMARY OBJECTIVE: I. Overall survival. SECONDARY OBJECTIVES: I. Progression-free survival. II. Objective tumor response. III. Comprehensive Geriatric Assessment (CGA)/quality of life (QOL) related objectives: IIIa. Hypothesize that lower scores in functional status assessment tool - instrumental activities of daily living (IADL) will correlate with higher rates of grade 3 or higher chemotherapy toxicity. IV. CGA/QOL related exploratory objectives: IVa. Evaluation of other pre-treatment CGA domains including co-morbidities, depression, nutrition and cognition as predictors of chemotherapy tolerance. IVb. Evaluation of the association between change in functional status during treatment course (comparison between activities of daily living \[ADL\] and IADL score pre-treatment and at time of disease evaluation) as predictors of chemotherapy tolerance. IVc. Evaluation of the correlation between CGA domains and overall survival by treatment arm. IVd. Evaluation of the difference in QOL scores (Functional Assessment of Cancer Therapy - Hepatitis \[FACT-Hep\] version 4) between baseline measures and assessment during treatment course between by treatment arms. V. Focused evaluation of toxicities that are of interest for older patients including: peripheral neuropathy, fatigue, falls, emergency room visits, hospitalization, treatment modification and discontinuation. VI. Imaging correlative study objectives: VIa. Evaluate the association between baseline and change during treatment of skeletal muscle index (SMI) and intermuscular adipose tissue (IMAT) and rates of grade 3 or higher chemotherapy toxicity experienced on treatment. VIb. Evaluate the association between baseline and change during treatment of skeletal muscle index (SMI) and intermuscular adipose tissue (IMAT) and overall survival among older patients with metastatic pancreatic cancer. VIc. Evaluate the association between baseline and change during treatment of skeletal muscle index (SMI) and intermuscular adipose tissue (IMAT) and geriatric assessment scores evaluating functional status. VII. Laboratory correlative study objectives: VIIa. Evaluation of the correlation between base line levels of biomarkers of aging (CRP and IL-6) and rates of grade 3 or higher chemotherapy toxicity during therapy. VIIb. Evaluation of the correlation between changes in levels of CRP and IL-6 during therapy and rates of grade 3 chemotherapy toxicity. VIIc. Evaluation of the correlation between baseline levels of biomarkers of aging (CRP and IL-6) and overall survival among older patients with metastatic pancreatic cancer. VIId. Evaluation of the correlation between levels of baseline biomarkers of aging (CRP and IL-6) and geriatric assessments scores evaluation functional status. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive gemcitabine intravenously (IV) over 30 minutes and nab-paclitaxel IV over 30 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive fluorouracil IV over 46 hours starting on day 1. Patients also receive leucovorin IV over 90-120 minutes and liposomal irinotecan IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years.