Patient description: The patient is a 57-year-old man with abdominal pain and vomiting. The pain started gradually about 20 hours ago in the epigastric and periumbilical regions, radiating to his back. He drinks around 60 units of alcohol per week and smokes 22 cigarettes per day. He is healthy with no history of allergies or using any medications. His family history is positive for type 2 diabetes (his father and sister). He lives alone and has no children. The abdomen is tender and soft. His bowel sounds are normal. His heart rate is 115/min and blood pressure 110/75 mmHg. The lab results are remarkable for leukocytosis (19.5), urea of 8.5, high CRP (145), high amylase (1200) and Glc level of 15. Cross-sectional imaging was negative for obstructive pancreatitis.

Clinical trial eligibility criteria: eligible ages (years): 18.0-999.0,  KRAS NP_004976.2:p.G12R Stage III Pancreatic Cancer AJCC v6 and v7 Stage IV Pancreatic Cancer AJCC v6 and v7 Patients must have histologically confirmed locally advanced or metastatic pancreas cancer Patients must have received at least 6 months fluorouracil (5-FU) or gemcitabine-based treatments for pancreas cancer (fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin [FOLFIRINOX], fluorouracil, leucovorin calcium and oxaliplatin [FOLFOX], 5-FU+ nal-IRI [MM-398; nanoliposomal irinotecan], or 5-FU [including capecitabine], gemcitabine-based gemcitabine plus abraxane, gemcitabine monotherapy among others) 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 for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) with conventional techniques or as >= 10 mm (>= 1 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam Patients must have Clinical Laboratory Improvement Act (CLIA) confirmed somatic Kirsten rat sarcoma (KRAS) G12R mutation as determined by sequence analysis of matched normal deoxyribonucleic acid (DNA) from any specimen obtained from the individual; patients must provide tumor sample for KRAS analysis or be willing to undergo mandatory screening biopsy Patients must not have had chemotherapy, molecular therapy with erlotinib, radiation therapy, or experimental biological or molecular therapy for at least 4 weeks prior to starting study medication; patients who received must be 6 weeks from the last administration of therapy; patients must have recovered from any acute toxicity related to prior therapy or surgery, to a grade 1 or less unless specified Eastern Cooperative Oncology Group (ECOG) performance status =< 1 or Karnofsky >= 70% Leukocytes >= 3,000/mcL Absolute neutrophil count >= 1,500/mcL Platelets >= 75,000/mcL  Patients who have received prior treatment with tyrosine kinase inhibitors (e.g. erlotinib), or anti-Epidermal growth factor receptor (EGFR) agents (e.g. cetuximab, panitumumab) Patients currently receiving any medication known to induce central serous chorioretinopathy which in the opinion of the principal investigator, would make the administration of study drug hazardous Patients with active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Any underlying medical condition which, in the opinion of the principal investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events Patients who are receiving any other investigational agents Patients with known brain metastases should be excluded from this clinical trial; no additional workup is needed to brain metastases if the patient is asymptomatic or has no history of brain metastases History of allergic reactions attributed to compounds of similar chemical or biologic composition to Selumetinib (AZD6244) or other agents used in study Previous Mitogen-activated protein kinase kinase (MEK), RAS, or Rapidly Accelerated Fibrosarcoma (RAF) inhibitor use Patients with the following cardiac conditions are excluded