Pediatric Low Grade Glioma - MEKinhibitor TRIal vs Chemotherapy

Inclusion Criteria:

• Age: ≥ 1 month to ≤ 25 years

• Signed written informed consent prior to study participation of the legal representatives and the patient if the patient can understand the impact of clinical trial and to give consent. For patients above 18 years, their written informed consent will be obtained.

• Patient may be under guardianship or curatorship (for patient under legal guardianship, authorization is given by the legal representative of the patient under guardianship. For patient under curatorship, consent will be obtained from the adult assisted by his or her legal curator

• Histologically proven grade 1 glioma/mixed glio-neuronal tumors or pleomorphic xanthoastrocytoma (PXA) confirmed by local referee and the centrally pathology reviewing

• Determination of a negative BRAFv600 mutation by immunohistochemistry and/or molecular methods

• Systematic determination 7q34 duplication status or KIAA1549-BRAF fusion

• Midline tumors without proven histone H3 mutations

• Diffuse glioma without IDH1 mutation

• Collection of fresh frozen tumor tissues and/or paraffin-embedded samples for further molecular biomarker testing

• Sus-tentorial, optic pathway, midline and spine locations allowed

• Karnofsky or Lansky ≥ 50%

• Criteria for post-surgical treatment: severe visual or neurological symptoms at diagnosis, clinical deterioration of visual or neurological symptoms or radiological progression. The radiological progression is defined as an increase of solid part of the tumor of more than 25% compared to the pre-baseline MRI-imaging over a time period of at least 3 months or the occurrence of new metastatic lesions.

• Infants below one year of age with chiasmatic and/or hypothalamic tumor will be treated immediately after surgery, independently from neurological and/or visual evolution

• Females of child-bearing potential must be willing to practice highly effective contraception during all treatment and until 6 months after the last dose of study drugs' administration. Additionally, females of child-bearing potential must have a negative serum pregnancy test within 7 days prior to start of study drugs. Boys with reproductive potential must be willing to use condom and consider contraception for partner women of childbearing potential during treatment and until 4 months after the last study drugs' administration.

• Patients must have adequate bone marrow function defined as: absolute neutrophil count (ANC) ≥ 1500/µL; platelets ≥ 100,000/µL and hemoglobin ≥ 9.0 g/dl

• Patients must have adequate liver function within 7 days prior to screening: bilirubin (sum of unconjugated and conjugated) ≤ 1.5 ULN for age, ALT and AST ≤ 2.5 x upper limit of normal, alkaline phosphatase ≤ 4 x upper limit of normal, INR/PTT < 1.5 x upper limit of normal,

• Patients must have adequate renal function within 7 days prior to screening: serum creatinine < 1.5 x upper limit of normal for age and a creatinine clearance > 60 ml/min for 1.73 m2

• Cardiac function defined as a corrected QT (QTcF) interval < 480 msec, LVEF ≥ lower limit of normal (LLN) by echocardiogram (ECHO)

• Adequate blood pressure control (smaller or equal to the 95th percentile for patient's age, height and gender)

• Patients are willing and able to comply with scheduled visits, treatment plan, laboratory tests and study procedures

• Guardians (in case of patients under 18 years) or patient if above 18 years must be affiliated to or a beneficiary of health insurance system.

Non-inclusion criteria

• Patients presenting a neurofibromatosis type 1 (NF1) congenital disease

• Pure optic nerve glioma, limited to one nerve and without optic chiasma infiltration.

• Completely resected tumors

• Previous treatment except tumor surgery

• Pregnancy and lactation

• Participation in other clinical trials

• Prior non-surgical therapy for this tumor

• Diffuse intrinsic pontine glioma (DIPG), even if histologically diagnosed as WHO grade II

• Subependymal giant astrocytoma (SEGA) in patients with TSC

• Patient having a known diagnosis of human immunodeficiency virus (HIV) infection, hepatitis B or C

• Known hypersensitivity to drugs or excipients

• History of another malignancy

• History of current uncontrolled infection