Trametinib and Hydroxychloroquine in Treating Patients With Pancreatic Cancer

Inclusion Criteria: * Male or female subject aged ≥ 18 years. * Subject with histologically confirmed metastatic or locally advanced, unresectable pancreatic carcinoma * Subject is willing to provide a baseline biopsy. * EXPANSION COHORT ONLY: Subject must have progressed during or after two standard of care lines of treatment or refused standard of care options. * Subject must have computed tomography (CT) measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria * Subject must be able and willing to undergo disease assessment while on study and afterwards, if removed for reason other than progression * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 * Adequate organ function as defined as: * Hematologic: * Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L * Platelet count \>= 100 x 10\^9/L * Hemoglobin \>= 9 g/dL * Hepatic: * Total bilirubin level =\< 1.5 x the upper limit of normal (ULN) range * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels =\< 3 x ULN. Patients with liver metastases will be allowed to enroll with AST and ALT levels =\< 5 x ULN * Renal: * Estimated creatinine clearance \>= 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method) * Negative serum or urine pregnancy test at screening for women of childbearing potential * Highly effective contraception for both male and female subjects throughout the study and fo…