Brief Summary: This phase Ib/II trial studies the side effects and best dose of pan fibroblast growth factor receptor (FGFR) kinase inhibitor BGJ398 when given together with fluorouracil, irinotecan hydrochloride and oxaliplatin (combination chemotherapy) in treating patients with untreated pancreatic cancer that has spread to another place in the body. Pan FGFR kinase inhibitor BGJ398 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil, irinotecan hydrochloride and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pan FGFR kinase inhibitor BGJ398 together with fluorouracil, irinotecan hydrochloride and oxaliplatin may be a better treatment for pancreatic cancer.

Detailed Description: PRIMARY OBJECTIVES: I. To determine dose-limiting toxicity, the maximum tolerated dose and recommended phase II dose of BGJ398 (pan FGFR kinase inhibitor BGJ398) administered in combination with modified (m)FOLFIRINOX (fluorouracil, irinotecan hydrochloride and oxaliplatin) in patients with advanced pancreatic and colorectal cancer patients. (Phase Ib) II. To determine the 6-month overall survival rate of patients with treatment-naïve metastatic pancreatic ductal adenocarcinoma treated with BGJ398 plus mFOLFIRINOX. (Phase II) SECONDARY OBJECTIVES: I. To determine the pharmacokinetic profile of BGJ398, fluorouracil, oxaliplatin, irinotecan (irinotecan hydrochloride) and their metabolites when administered in combination and explore for drug-drug interactions. (Phase Ib) II. To determine the 1-year overall survival rate, response rate, progression free survival and cancer antigen (CA)19-9 changes in treatment-naïve metastatic pancreatic cancer patients treated with BGJ398 plus mFOLFIRINOX. (Phase II) III. To determine the safety and tolerability of BGJ398 in combination with mFOLFIRINOX in the study population. IV. To explore plasma and tumor biomarkers associated with efficacy to the study combination. OUTLINE: This is a phase Ib, dose-escalation study of pan FGFR kinase inhibitor BGJ398 followed by a phase II study. Patients receive oxaliplatin intravenously (IV) over 2 hours, irinotecan hydrochloride IV over 90 minutes, and fluorouracil IV continuously over 46 hours on days 1 and 15. Patients also receive pan FGFR kinase inhibitor BGJ398 orally (PO) once daily (QD) on days 8-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 28 days and then every 4 months for up to 2 years.