Ibrutinib Combined With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Pancreatic Cancer

Inclusion Criteria: * Histologically or cytologically confirmed metastatic pancreatic adenocarcinoma * Stage IV disease (measurable disease NOT required) * Intact primary tumor * CA19-9 greater than 75 units * Eastern Cooperative Oncology Group (ECOG) performance score of 0-1 * At least 18 years of age * Female patients who are not of child-bearing potential, and fertile female patients of child-bearing potential, who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to start of randomization. * Fertile male patients willing to use adequate contraceptive measures. * Adequate bone marrow function: * Absolute neutrophil count (ANC) ≥ 1500/microliter (uL) * platelet count ≥ 100,000/uL * hemoglobin ≥ 9.0 g/dL * Adequate hepatic function: * Total bilirubin ≤ 1.5 X ULN (unless bilirubin rise due to Gilbert's syndrome) * Aspartate amino transferase (AST) (SGOT) ≤ 3.0 X ULN; ≤5.0X ULN if liver metastases are present. * Alanine aminotransferase (ALT) (SGPT) ≤ 3.0 X ULN; ≤0 5.0X ULN if liver metastases are present. * Adequate renal function (defined as serum creatinine ≤ 1.5 X ULN) * Ability to understand the nature of this study protocol, comply with study and/or follow-up procedures, and give written informed consent * Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. Exclusion Criteria: * Any prior systemic or investigational therapy for metastatic pancreatic cancer. Systemic therapy administered alone or in combination with radiation in the adjuvant or neoadjuvant setting is permissible as long as it was completed \> 6 months prior to the time of study registration. * History of other diseases, metabolic dysfunction, physical examination findings, or clinical laboratory findings giving reasonable suspicion of a disease or condition that, in the opinion of the investigator, renders the subject at high risk from treatment complications or might affect the interpretation of the results of the study. * History of previous malignancy (except basal cell) within 5 years. * Life expectancy of \<3 months. * Inability to undergo two sequential Endoscopic Ultrasound (EUS)-directed core biopsies of the primary tumor. * Presence of known central nervous system or brain metastases. * Known human immunodeficiency virus (HIV) infection. * History of stroke or intracranial hemorrhage within 6 months prior to enrollment. * Known bleeding disorders (e.g., von Willebrand's disease or hemophilia). * Patients receiving warfarin or other Vitamin K antagonists. However, if therapeutic anticoagulation is necessary, low molecular weight heparin (LMWH) is the anticoagulant of choice. * Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization. * Current peripheral sensory neuropathy \> Grade 1 * Major surgery within 4 weeks of the start of study treatment (defined as those surgeries that require general anesthesia. Insertion of a vascular access device is NOT considered major surgery. * Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor. * Unable to swallow capsules or has malabsorption syndrome, disease significantly affecting gastrointestinal function or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.