MEK162, Phase I-II Study of MEK 162 for Children with Low-Grade Gliomas and Other Ras/Raf/ERK Pathway Activated Tumors

Phase I * Patients with recurrent, refractory, or progressive non-hematologic malignancies (central nervous system (CNS) or solid tumors) associated with activation of the RAS/RAF/ERK (guanosine triphosphatase protein/murine leukemia viral oncogene homolog/extracellular regulated signal kinase) pathway, including any low-grade glioma (LGG), any tumor in a patient with neurofibromatosis type 1 (NF1), or any tumor with a documented activating BRAF (B-Raf proto-oncogene serine/threonine-protein kinase), NRAS (neuroblastoma RAS viral (v-ras) oncogene homolog), or KRAS (kirsten rat sarcoma viral oncogene homolog) mutation, will be eligible. LGG is defined as any World Health Organization (WHO) grade I or II (or equivalent) astrocytic, oligodendroglial, and/or glioneuronal tumor. Phase II * Patients with recurrent or progressive disease as defined in the following three strata below, will be eligible: * Stratum 1: patients with low-grade gliomas with a BRAF truncated fusion that is measurable in at least two dimensions on imaging. * Stratum 2: patients with NF1 and LGG that is measurable in at least two dimensions on imaging. * Stratum 3: Pediatric patients with recurrent or progressive tumors thought to involve the Ras/Raf/ERK pathway but not included in strata 1 or 2 that is measurable in at least two dimensions on imaging. This includes any LGG not included in strata 1 or 2 (i.e., any LGG without a BRAF truncated fusion in a patient without NF1), any tumor other than LGG in a patient with NF1, and any other tumor with a documented activating BRAF, NRAS, or KRAS mutation. * Stratum 4 (surgical arm, target validation): Patients who meet criteria for stratum 1, 2, or 3) for whom tumor biopsy and/or resection is clinically indicated. * Tumor tissue for correlative studies must be available for all patients except those with NF1 and LGG (stratum 2) or any patient with optic pathway glioma (stratum 2 or 3), for whom tumor tissue is optional. * Patients must have received at least one prior chemotherapy or radiation regimen prior to progression. The remaining criteria apply for all phases: * Patients must be >= 1 year and < 18 years old. * Performance Score using the Karnofsky Performance Scale (patients > 12 years old) or Lansky Play-Performance Scale (patients <= 12 years old) must be >= 60 assessed within two weeks prior to enrollment. * Participants must have normal organ and marrow function as defined below within two weeks prior to enrollment: * Absolute neutrophil count >= 1,000/mcL. * Platelets >= 75,000/mcL and > 7 days since last platelet transfusion. Hemoglobin >= 9gm/dL and > 7 days since last red blood cell transfusion. * Not refractory to red cell or platelet transfusions. * Hepatic: Total bilirubin <= 1.5 times the upper limit of normal; serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase - ALT) and serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase - AST) <= 3 times the institutional upper limit of normal. * Renal: Serum creatinine which is less than 1.5 time the upper limit of institutional normal for age or glomerular filtration rate (GFR) > 70 ml/min/1.73m2. * QTc interval <= 450ms. * Left ventricular ejection fraction (LVEF) >= 50% as determined by a echocardiogram. * Female patients of childbearing potential must have negative serum or urine pregnancy test within 72 hours of the first dose of MEK162. Patient must not be pregnant or breastfeeding. Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study and for 30 days following cessation of treatment. * Patient must be able to take oral/enteral medication. * Patient, parent, or legal guardian must be able to understand and willing to provide informed consent. * Patients must have recovered from the effects of prior therapy.