Binimetinib and Hydroxychloroquine in Treating Patients With KRAS Mutant Metastatic Pancreatic Cancer

Inclusion Criteria

• •Have histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma based on pathology report with radiologically identified metastases that meet Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
• •Be willing and able to provide written informed consent for the trial.
• •Have at least one measurable lesion by RECIST criteria.
• •Have had prior treatment with at least one line of therapy for metastatic disease.
• •Have had tumor mutation profiling from any Clinical Laboratory Improvement Act (CLIA) certified laboratory demonstrating a KRAS mutation. Liquid biopsy demonstrating KRAS mutation will be considered acceptable.
• •Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale.
• •Absolute neutrophil count (ANC) \>= 1500/uL (specimens must be collected within 10 days prior to the start of trial treatment).
• •Platelets \>= 100,000/uL (specimens must be collected within 10 days prior to the start of trial treatment).
• •Hemoglobin \>= 9.0 g/dL (specimens must be collected within 10 days prior to the start of trial treatment).
• •Creatinine OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) =\< 1.5 x upper limit of normal (ULN) OR \>= 50 mL/min for subjects with creatinine level \> 1.5 x ULN (specimens must be collected within 10 days prior to the start of trial treatment).
• •Total bilirubin =\< 1.5 x ULN (specimens must be collected within 10 days prior to the start of trial treatment).
• •Indirect bilirubin =\< ULN (specimens must be collected within 10 days prior to the start of trial treatment).
• •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]), and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN (=\< 5 x ULN for subjects with liver metastases) (specimens must be collected within 10 days prior to the start of trial treatment).
• •Alkaline phosphatase =\< 2.5 x ULN (=\< 5 x ULN for subjects with liver metastases) (specimens must be collected within 10 days prior to the start of trial treatment).
• •Serum albumin \> 3.3 mg/dl (specimens must be collected within 10 days prior to the start of trial treatment).
• •International normalized ratio (INR) OR prothrombin time (PT), activated partial thromboplastin time (aPTT) =\< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants (specimens must be collected within 10 days prior to the start of trial treatment).
• •Female subjects of childbearing potential must have a negative urine or serum pregnancy test prior to the start of treatment.
• •The participant is deemed by the investigator to have the ability to be compliant with scheduled visits, treatment plan, and study procedures.
• •Male and female subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of trial therapy through 30 days after the last dose of trial therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. Acceptable methods of contraception are listed in the protocol text.
• •Has a known history of active TB (Mycobacterium Tuberculosis).
• •Is unable to tolerate a contrast enhanced computed tomography (CT) or magnetic resonance imaging (MRI) for staging/restaging purposes.
• •In the estimation of the treating physician or primary investigator, have had a clinical deterioration of their ECOG performance within the month prior to enrollment. Evidence for such deterioration shall be documented in the patient's medical record.
• •Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. Evidence for such abnormalities/conditions will be documented in the patient's medical record.
• •Has a history of thromboembolic or cerebrovascular events =\< 12 weeks prior to the first dose of study treatment. Examples include transient ischemic attacks, cerebrovascular accidents, hemodynamically significant (i.e. massive or sub-massive) deep vein thrombosis or pulmonary emboli. Note: Patients with either deep vein thrombosis or pulmonary emboli that does not result in hemodynamic instability are allowed to enroll as long as they are on a stable dose of anticoagulants for at least 4 weeks. Also note: Patients with thromboembolic events related to indwelling catheters or other procedures may be enrolled. Finally: patients with stable mesenteric thrombosis that predate study assessment (eg portal vein thrombus) may be enrolled.
• •Has a history of active bleeding requiring transfusion within a 3 month period prior to screening. (Transfusions attributed to chemotherapy related anemia do not meet this exclusion criterion.)
• •Known cases of drug-induced hepatobiliary toxicities (other than a radiological finding of fatty liver).
• •Has had prior treatment with a MEK or ERK inhibitor.
• •Partial or complete bowel obstruction.
• •Impaired gastrointestinal function that may significantly alter the absorption of binimetinib (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption) or baseline diarrhea \>= grade 1.
• •Use of digoxin, mefloquine, cyclosporine, methotrexate, fexofenadine, quinidine, talinolol, vinblastine, coumestrol, daidzein, dantrolene, estrone-3-sulfate, genistein, prazosin, sulfasalazine, or antiepileptics if used for seizures (ok to use the latter if part of a pain regimen). Prior loperamide use for diarrhea is permitted at enrollment but should be changed to diphenoxylate / atropine before initiation of treatment.
• •Has a history of psoriatic arthritis requiring systemic treatment.
• •Has a history of porphyria.
• •(Expansion phase only) Inability to safely undergo tumor biopsies (e.g. requirement for antiplatelet therapy).