Regorafenib Plus Gemcitabine in Metastatic Pancreatic Cancer

Inclusion Criteria: * Patients must have histologically or cytologically confirmed metastatic pancreatic adenocarcinoma (or any mixed pathology if adenocarcinoma is predominant) * Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \> 20 mm with conventional techniques or as \> 10 mm with spiral computed tomography (CT) scan * Prior Therapies: Patients must have received at least one prior systemic chemotherapy regimen for metastatic pancreatic cancer. They should have experienced disease progression or intolerable toxicity from that regimen. * Patients who have received prior non-gemcitabine-based systemic chemotherapy for metastatic disease at any time 4 weeks prior to enrollment, or those who are beyond 12 months of exposure to gemcitabine-based chemotherapy regimen are allowed. * Prior chemotherapy, radiation therapy, concurrent chemoradiation are allowed if used for treatment of non-metastatic disease. * Any chemotherapy must have been completed 4 weeks prior to enrollment * Any radiotherapy must have been completed 2 weeks prior to enrollment * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Life expectancy of at least 12 weeks (3 months) * Subjects must be able to understand and be willing to sign the written informed consent form; a signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure * All acute toxic effects of any prior treatment have resolved to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version (v)4.0 grade 1 or less at the time of signing the informed consent form (ICF) * Total bilirubin =\< 1.5 x the upper limits of normal (ULN) * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x ULN (=\< 5 x ULN for subjects with liver involvement of their cancer) * Alkaline phosphatase limit =\< 2.5 x ULN (=\< 5 x ULN for subjects with liver involvement of their cancer) * Lipase =\< 1.5 x the ULN * Serum creatinine =\< 1.5 x the ULN * International normalized ratio (INR)/partial thromboplastin time (PTT) 1.5 x ULN; (subjects who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists; close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care) * Platelet count \>= 100000/mm\^3, hemoglobin (Hb) ≥ 9 g/dL, absolute neutrophil count (ANC) ≥ 1500/mm\^3; blood transfusion to meet the inclusion criteria will not be allowed * Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug; post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test * Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the ICF until at least 3 months after the last dose of study drug; the definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate * Subject must be able to swallow and retain oral medication Exclusion Criteria: * Chemotherapy within 4 weeks prior to entering the study, radiotherapy within 2 weeks prior to entering the study or failure to recover from adverse events to grade 1 or less due to agents administered more than 4 weeks earlier * Use of any other investigational agents * Previous assignment to treatment during this study; subjects permanently withdrawn from study participation will not be allowed to re-enter study * Uncontrolled hypertension (systolic pressure \> 140 mm Hg or diastolic pressure \> 90 mm Hg \[NCI-CTCAE v4.0\] on repeated measurement) despite optimal medical management * Active or clinically significant cardiac disease including: * Congestive heart failure - New York Heart Association (NYHA) \> class II * Active coronary artery disease * Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin * Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before randomization, or myocardial infarction within 6 months before randomization * Evidence or history of bleeding diathesis or coagulopathy * Any hemorrhage or bleeding event \>= NCI CTCAE grade 3 within 4 weeks prior to start of study medication * Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) deep vein thrombosis or pulmonary embolism within 6 months of informed consent * Subjects with any previously untreated or concurrent cancer that is distinct in primary site or histology from pancreatic cancer except cervical cancer in-situ, treated basal cell carcinoma, or superficial bladder tumor; subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before randomization are allowed; all cancer treatments must be completed at least 3 years prior to study entry (i.e., signature date of the informed consent form) * Patients with phaeochromocytoma * Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy * Any infection requiring ongoing intravenous antibiotics for management * Symptomatic metastatic brain or meningeal tumors; treated and stable, asymptomatic brain metastases, as long as treatment was greater than 4 weeks prior to informed consent, are allowed * Presence of a non-healing wound, non-healing ulcer, or bone fracture * Renal failure requiring hemo-or peritoneal dialysis * Dehydration grade \>= 1 NCI-CTCAE v4.0 * Patients with seizure disorder requiring medication * Persistent proteinuria \>= grade 3 NCI-CTCAE v4.0 (\> 3.5 g/24 hrs, measured by urine protein:creatinine ratio on a random urine sample) * Interstitial lung disease with ongoing signs and symptoms at the time of informed consent * Pleural effusion or ascites that causes respiratory compromise (\>= NCI-CTCAE version 4.0 grade 2 dyspnea) * History of organ allograft (including corneal transplant) * Known or suspected allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial * Any malabsorption condition * Women who are pregnant or breast-feeding * Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation * Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results