[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"pleomorphic-xanthoastrocytoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:pleomorphic-xanthoastrocytoma":30},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,3,0,[8,47,93],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":35,"lastUpdatePostDateStruct":36,"startDateStruct":39,"completionDateStruct":41,"leadSponsor":43,"locationsCount":46},"100367552","evaluation-of-hippocampal-avoidance-using-proton-therapy-in-low-grade-glioma-100367552",false,"NCT04065776","Evaluation of Hippocampal-Avoidance Using Proton Therapy in Low-Grade Glioma","A Phase II Study of Hippocampal-Avoidance Using Proton Therapy in Low-Grade Glioma","Inclusion Criteria:\n\n* Patients must have a diagnosis of pilocytic astrocytoma, pilomyxoid astrocytoma, pleomorphic xanthoastrocytoma, ganglioglioma, optic pathway glioma, diffuse astrocytoma, low-grade neuroepithelial tumor, low-grade glioneuronal tumor or LGG, or not otherwise specified (NOS).\n* Patient with eligible diagnosis other than optic pathway glioma or tumors of the brainstem\u002Fmidbrain\u002Ftectum has histologic verification of disease at diagnosis or recurrence OR\n* Patient with optic pathway glioma or tumors of the brainstem\u002Fmidbrain\u002Ftectum has radiologic verification of disease at diagnosis or recurrence\n* A repeat biopsy was done because the recurrent tumor was enhancing but did not originally enhance because there was a high index of suspicion regarding high-grade transformation\n* Tumor must be located in the suprasellar region or midline structures. Midline structures include, but are not limited to, the thalamus, basal ganglia, internal capsule, midbrain, tectum, third ventricle, fourth ventricle, cerebellum, pons, and medulla. Tumors may involve the optic pathway. For questions about tumor locations that are not specified on this list, please contact the Study PI.\n* Patients must be at least 6 years but less than 22 years of age at the time of enrollment.\n* Patients must have a performance status greater or equal to 70 (use Karnofsky scale for patients aged 16 years and older and Lansky scale for patients aged less than 16 years).\n* Patients may not receive concurrent chemotherapy or targeted therapy, including but not limited to BRAF-inhibitors and MEK-inhibitors.\n* All patients must be able to undergo contrast-enhanced brain MRI.\n* All patients must have adequate organ function as described below.\n\n  * Peripheral absolute neutrophil count (ANC) ≥ 1000\u002FµL\n  * Platelet count ≥ 10,000\u002FµL (transfusion independent)\n  * Patients with seizures may be enrolled if well controlled on anticonvulsants\n\nExclusion Criteria:\n\n* Patients may not have received prior CNS radiation.\n* Patients with gross total resection and no measurable disease via MRI are not eligible. Patients must have measurable disease of at least 1 cm via MRI.\n* Patients with evidence of metastatic disease are not eligible.\n* Patients with WHO grade II midline tumors that harbor the H3K27M mutation, IDH-mutant gliomas, grade II ependymomas and subependymomas, pituicytomas, spindle cell oncocytomas, or granular cell tumors of the sellar region are not eligible.\n* Patients with tumors that directly invade the hippocampus or with gross tumor volumes that extend into the hippocampus are not eligible.\n* Patients with tumors in the spine or cervicomedullary junction.\n* Females of child-bearing potential cannot be pregnant or breast feeding. Female participants \\> 10 years of age or post menarche must have a negative serum or urine pregnancy test before enrollment. Males and females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.\n* Patients who are status post resection of bilateral hippocampi. Patients who are status post resection of one hippocampus will be eligible for the study and the hippocampal dose constraints will be applied to the intact hippocampus.","ALL","6 Years","21 Years",{"count":20,"type":21},74,"ESTIMATED","INTERVENTIONAL",[24],"NA","Low-grade gliomas (LGGs) are the most common brain tumors in children, and a subset of these tumors are treated definitively with focal radiation therapy (RT). These patients often survive for many years after receiving RT and experience late deficits in memory. Verbal recall is an important measure of memory and is associated with other important functional outcomes, such as problem-solving, independence of every-day functioning, and quality of life. Decline in memory, as measured by verbal recall, is associated with RT dose to the hippocampi. Therefore, this phase II study investigates the feasibility of reducing RT doses to the hippocampi (i.e., hippocampal avoidance \\[HA\\]) by using proton therapy for midline or suprasellar LGGs.\n\nPrimary Objective:\n\n* To determine the feasibility of HA with proton therapy in suprasellar or midline LGGs. Feasibility will be established if 70% of plans meet the first or second dose constraints shown below.\n\n  1. First priority RT dose constraints for bilateral hippocampi: volume receiving 40 CGE (V40CGE) ≤ 25%, dose to 100% of Hippocampus (D100%) ≤ 5CGE.\n  2. Second priority RT dose constraints for bilateral hippocampi: V40CGE ≤ 35%, D100% ≤ 10 CGE.\n\n     Secondary Objectives:\n* To estimate the 3-year event-free-survival (EFS) for LGGs treated with HA.\n* To estimate the change in California Verbal Learning Test short-term delay (CVLT-SD) from baseline to 3 years and from baseline to 5 years\n* To compare CVLT-SD and Cogstate neurocognitive scores in patients with proton therapy plans that: (1) meet first priority RT dose constraints, (2) meet second priority RT dose constraints but not first priority RT dose constraints, and (3) that did not meet either first or second RT priority dose constraints\n\nExploratory Objectives:\n\n* To describe the change in overall cognitive performance from baseline to 3 years and from baseline to 5 years with an age appropriate battery, including gold standard measures shown in the published studies to be sensitive to attention, memory processing speed and executive function that will afford comparison to historical controls.\n* To characterize longitudinal changes in connection strength within brain networks in the first 3 years after proton therapy and to investigate associations between these changes and neurocognitive performance with focus on the hippocampi.\n* To correlate the distribution and change in L-methyl-11C-methionine positron emission tomography (MET-PET) uptake to tumor progression and from baseline to 3 years and to investigate whether cases of pseudoprogression exhibit a differential pattern of uptake and distribution compared to cases of true progression after controlling for histology.\n* To investigate the effect of BRAF alteration, tumor histology and tumor location on PFS and OS in a prospective cohort of patients treated in a homogenous manner.\n* To investigate whether the methylation profiles of LGGs differ by tumor location (thalamic\u002Fmidbrain vs. hypothalamic\u002Foptic pathway vs. others) and histologies (pilocytic astrocytoma vs. diffuse astrocytoma vs. others), which, in conjunction with specific genetic alterations, may stratify patients into different subgroups and highlight different therapeutic targets.\n* To record longitudinal measures of circulating tumor DNA (ctDNA) in plasma and correlate these measures with radiographic evidence of disease progression.\n* To bank formalin-fixed, paraffin-embedded (FFPE)\u002Ffrozen tumors and whole blood from subjects for subsequent biology studies not currently defined in this protocol.\n* To quantify and characterize tumor infiltrating lymphocytes (TILs) and to characterize the epigenetics of T cells and the T cell receptor repertoire within the tumor microenvironment.\n* To estimate the cumulative incidence of endocrine deficiencies, vision loss, hearing loss and vasculopathy after proton therapy and compare these data to those after photon therapy.",[27,28,29,30,31,32,33],"Glioma","Pilocytic Astrocytoma","Pilomyxoid Astrocytoma","Pleomorphic Xanthoastrocytoma","Ganglioglioma","Optic Pathway Glioma","Diffuse Astrocytoma","RECRUITING","2026-06-15",{"date":37,"type":38},"2026-06-17","ACTUAL",{"date":40,"type":38},"2019-08-28",{"date":42,"type":21},"2028-07",{"name":44,"class":45},"St. Jude Children's Research Hospital","OTHER",2,{"id":48,"slug":49,"hasResults":11,"nctId":50,"briefTitle":51,"officialTitle":52,"acronym":4,"eligibilityCriteria":53,"healthyVolunteers":11,"sex":16,"minAge":54,"maxAge":4,"enrollmentInfo":55,"targetDuration":4,"studyType":22,"phases":57,"briefSummary":59,"conditions":60,"keywords":81,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":82,"lastUpdatePostDateStruct":83,"startDateStruct":85,"completionDateStruct":87,"leadSponsor":89,"locationsCount":92},"100404034","phase-1-phase-i-study-of-oral-onc206-in-recurrent-and-rare-primary-central-nervous-system-neoplasms-100404034","NCT04541082","Phase I Study of Oral ONC206 in Recurrent and Rare Primary Central Nervous System Neoplasms","A First-in-human Phase I Single-agent Dose-escalation, Food Effect and Dose Expansion Study of Oral ONC206 in Recurrent and Rare Primary Central Nervous System Neoplasms","Inclusion Criteria:\n\nPatients must meet all the following criteria to participate in the study:\n\n1. Patients aged ≥18 years with a recurrent, primary CNS neoplasm. For all cohorts, patients must have a histologically confirmed primary CNS neoplasm. Primary CNS neoplasms in this study include, but are not limited to, the following: glioblastoma and glioblastoma histologic subtypes, gliosarcoma, primary CNS sarcomas, anaplastic glial neoplasms including anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed neuronal-glial tumors, and pilocytic astrocytoma with anaplastic features, diffuse astrocytoma, oligodendroglioma, gliomatosis cerebri, pleomorphic xanthoastrocytoma, anaplastic pleomorphic xanthoastrocytoma, diffuse midline gliomas and histone mutated gliomas (NOTE: Patients with H3 K27M-mutant diffuse gliomas are excluded unless the primary tumor is located in the pons or spinal cord, or the patient has completed front line radiation or received ONC201 therapy prior to 01 January 2023), ependymoma, anaplastic ependymoma, and all ependymoma subtypes, medulloblastoma and all medulloblastoma subtypes, atypical teratoid\u002Frhabdoid tumor, primary CNS embryonal\u002Fprimitive neuroectodermal tumors, atypical and anaplastic meningiomas, choroid plexus tumors, and pineal region tumors.\n2. Patients must have recurrent and measurable disease as defined by RANO criteria, using either the HGG and\u002For LGG RANO criteria based on tumor type, after having received established standard of care treatment for their disease and have no standard treatment options available as determined by the investigators. There is no limit on the number of total recurrences or prior therapies. However, prior therapies with known clinical benefit (including radiation) for specific tumor types are required. If patients are deemed ineligible for such therapies in the opinion of the Investigator, the Investigator must document the reason the patient is considered ineligible.\n3. Patients must have a Karnofsky Performance Score (KPS) of greater than or equal to 70. Patients with severe paraparesis\u002Fparaplegia who need minimal assistance for self-care due to their motor deficit but are otherwise functionally independent will be considered eligible.\n4. (Inclusion Criterion #4 was removed in Amendment 3.)\n5. Patients must not have received prior investigational or approved cytotoxic chemotherapy within 28 days prior to the first dose of study drug (Cycle 1, Day 1); 42 days in the case of nitrosoureas; 42 days in the case of bevacizumab; 28 days or 5 half-lives (whichever is less; but not less than 14 days) in case of investigational or approved molecularly targeted agent; 14 days in the case of radiotherapy.\n6. (Inclusion Criterion #6 was removed in Amendment 7.)\n7. Patients with AEs Grade ≥2 related to prior therapies (chemotherapy, radiotherapy, and\u002For surgery) must have all their AEs resolved prior to the first dose of study drug (Cycle 1, Day 1), except for alopecia or neuropathy; Grade 1 or 2 lymphopenia is allowed.\n8. Patients must not have undergone major surgery 4 weeks prior to the first dose of study drug (Cycle 1, Day 1) and must have completely recovered from any surgery (minor surgical procedures such as skin biopsies and port placement done on an outpatient basis do not require a waiting period).\n9. Patients must have normal organ and marrow function as defined below:\n\n   * Absolute neutrophil count (ANC) ≥1,500\u002FmcL.\n   * Platelets ≥100,000\u002FmcL.\n   * Hemoglobin ≥9.0 mg\u002FdL without transfusion in 2 prior weeks.\n   * Total bilirubin ≤1.5 × upper limit of normal (ULN) (patients with Gilbert's syndrome may be included with total bilirubin \\>1.5 × ULN if direct bilirubin is ≤1.5 × ULN).\n   * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤2.5 × ULN.\n   * Measured or estimated creatinine clearance (CLcr) ≥40 mL\u002Fminute for patients with creatinine levels above normal. CLcr will be calculated by the Cockcroft-Gault equation for renal function.\n10. (Inclusion Criterion #10 was removed in Amendment 3)\n11. Patients must provide a tumor specimen (paraffin-embedded block and\u002For frozen tissue) from a prior resection or biopsy available that is sufficient to perform biomarker assays, ≥15 unstained slides for immunohistochemistry (IHC) analysis must be received by the NOB by the first dose of study drug (Cycle 1, Day 1). For patients with ≥10 to \\\u003C15 slides, eligibility will be reviewed on a case-by-case basis.\n12. Dependent upon dose level assignment and drug formulation (i.e., capsules versus powder in bottle \\[PIB\\]), patients must be able to either swallow oral capsules or swallow liquids.\n13. Patients must provide study-specific informed consent prior to enrollment. No Durable Power of Attorney or Next of Kin can provide initial consent.\n14. Patients must be able to tolerate a magnetic resonance imaging (MRI) study with intravenous gadolinium contrast.\n15. (Inclusion Criterion #15 was removed in Amendment 6)\n16. Patients must have a negative COVID-19 test within 72 hours of the first dose of study drug (Cycle 1, Day 1). Patients who had documented COVID-19 infection within 90 days of treatment but more than 20 days from infection do not need to be tested.\n17. (Inclusion Criterion #17 was removed in Amendment 6)\n\nExclusion Criteria:\n\nPatients who meet any of the following criteria will be excluded from the study:\n\n1. (Exclusion Criterion #1 was removed in Amendment 3)\n2. Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC206 (e.g., ONC201) or its excipients.\n3. Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n4. Patients who are unable or unwilling to abide by the study protocol or cooperate fully with the Investigator.\n5. Patients with a known HIV-positive test on combination anti-retroviral therapy are ineligible for this initial first-in-human trial because of the potential for PK interactions with ONC206.\n6. Patients with active cardiac disease, including any of the following:\n\n   * Corrected QT interval (QTc) ≥470 msec on screening electrocardiogram (ECG; using the QTc by Fridericia's \\[QTcF\\] formula);\n   * Angina pectoris that requires the use of anti-anginal medication;\n   * Ventricular arrhythmias except for benign premature ventricular contractions;\n   * Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication;\n   * Conduction abnormality requiring a pacemaker;\n   * Valvular disease with documented compromise in cardiac function; and\u002For\n   * Symptomatic pericarditis.\n7. Patients with a history of cardiac dysfunction including any of the following:\n\n   * Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular ejection fraction function;\n   * History of documented congestive heart failure (New York Heart Association functional classification III-IV); and\u002For\n   * Documented cardiomyopathy.\n8. Patients who have had an ischemic or hemorrhagic stroke in the last 3 months. If the patient has had a recent tumor resection, cerebral ischemic or hemorrhagic changes that occur peri operatively are not an exclusion.\n9. Patients with refractory epilepsy are excluded. Patients with primarily or secondarily generalized seizures in the 28 days prior to study enrollment will be excluded. Peri-operative seizures, defined as seizures occurring within the 7 days after a stereotactic biopsy, open biopsy, or surgical resection will not be an exclusion as long as the patient has had no generalized seizures starting 8 days after the surgical procedure. Patients with prior seizures must be on stable doses of 1 or 2 seizure medications for at least 14 days prior to study enrollment.\n10. Patients with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of ONC206 (uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).\n11. Patients who have been treated with any hematopoietic colony-stimulating growth factors (CSFs) (e.g., granulocyte-CSF, granulocyte-macrophage-CSF) ≤2 weeks prior to starting study drug. Erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued.\n12. Patients who are currently taking therapeutic doses of warfarin sodium or any other coumadin derivative anticoagulant.\n13. Patients who are taking strong inhibitors or inducers of cytochrome P450 (CYP) 3A4, 2D6, 1A2, 2C9, and 2C19 within at least 14 days prior to the first dose of study drug (Cycle 1, Day 1); these medications are excluded throughout the study.\n14. Women who are pregnant or breast feeding.\n15. Women of child-bearing potential with a positive serum pregnancy test ≤72 hours prior to the first dose of study drug (Cycle 1, Day 1).\n16. Patients who are receiving concomitant standard and\u002For investigational anti-cancer therapy.\n17. Patients with alcohol or substance abuse which, in the opinion of the Investigator, would interfere with compliance or safety.\n18. Patients with the presence of any other serious and\u002For unstable pre-existing medical disorder, psychiatric disorder, or other conditions that could interfere with patients' safety, obtaining informed consent or compliance to the study procedures as determined by the Investigators.\n19. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, or men who do not agree to use highly effective contraception during treatment and for 16 additional weeks after the final dose of study drug.\n\n    Highly effective contraception is defined as either:\n    * True abstinence: When this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.\n    * Sterilization: Females must have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks ago. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.\n    * Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). For female patients on the study, the vasectomized male partner should be the sole partner for that patient.\n    * If patients are not practicing true abstinence and\u002For if the patient or sexual partner have not had a sterilization procedure as listed above, patients and their sexual partners must follow double barrier contraception in accordance with the guidelines for contraception below:\n\n      * Females of childbearing potential:\n\n        * Must use an intrauterine device or intrauterine system, during dosing of any study agent and for 16 weeks after final dose of study drug; or\n        * Must use a double barrier method of contraception: use of an occlusive cap (diaphragm or cervical\u002Fvault cap) with spermicide for women combined with use of a condom by their male partners capable of conceiving offspring.\n      * Males capable of conceiving offspring must use condoms during dosing of study agent and for an additional 16 weeks after final dose of study drug.\n\n    Note: Oral, implantable, or injectable contraceptives may be affected by CYP interactions, and are therefore not considered effective for this study.\n20. Previous receipt of ONC201, placebo, or blinded study drug from an ONC201 clinical study, or from any other source for H3 K27M-mutant diffuse glioma on or after 01 January 2023.","18 Years",{"count":56,"type":21},102,[58],"PHASE1","The primary objective of this Phase 1, open-label, dose-escalation, and exploratory study is to evaluate the safety and tolerability profile (establish the maximum-tolerated dose) and evaluate the occurrence of dose-limiting toxicities (DLTs) following single weekly or multiple-day weekly dose regimens of single-agent, oral ONC206 in patients with recurrent, primary central nervous system (CNS) neoplasms.",[61,62,63,64,65,28,66,67,30,68,69,70,71,72,73,74,75,76,77,78,79,33,80],"Central Nervous System Neoplasms","Glioblastoma","Gliosarcoma, Adult","Anaplastic Oligodendroglioma","Anaplastic Astrocytoma","Oligodendroglioma","Gliomatosis Cerebri","Anaplastic Pleomorphic Xanthoastrocytoma","Diffuse Midline Glioma, H3 K27M-Mutant","Ependymoma","Ependymoma, Anaplastic","Medulloblastoma","Teratoid Rhabdoid Tumor","Neuroectodermal Tumors, Primitive","Neuroectodermal Tumors","Anaplastic Meningioma","Atypical Meningioma","Choroid Plexus Neoplasms","Pineal Tumor","Glial Tumor",[62,65,64,33,66],"2025-12-17",{"date":84,"type":38},"2025-12-18",{"date":86,"type":38},"2020-10-26",{"date":88,"type":21},"2026-12",{"name":90,"class":91},"Jazz Pharmaceuticals","INDUSTRY",1,{"id":94,"slug":95,"hasResults":11,"nctId":96,"briefTitle":97,"officialTitle":98,"acronym":99,"eligibilityCriteria":100,"healthyVolunteers":11,"sex":16,"minAge":101,"maxAge":102,"enrollmentInfo":103,"targetDuration":4,"studyType":22,"phases":105,"briefSummary":107,"conditions":108,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":111,"lastUpdatePostDateStruct":112,"startDateStruct":114,"completionDateStruct":116,"leadSponsor":118,"locationsCount":120},"100453153","phase-2-pediatric-low-grade-glioma---mekinhibitor-trial-vs-chemotherapy-100453153","NCT05180825","Pediatric Low Grade Glioma - MEKinhibitor TRIal vs Chemotherapy","A Randomized and Controlled Phase II Protocol in Non NF1 Pediatric and AYA (Adolescent and Young Adults) Patients Bearing a Newly Diagnosed Low Grade Glioma With Wild Type BRAF Gene Comparing a Daily Oral MEK Inhibitor (Trametinib) Versus Weekly Vinblastine for 18 Months","PLGG - MEKTRIC","Inclusion Criteria:\n\n* Age: ≥ 1 month to ≤ 25 years\n* 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.\n* 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\n* Histologically proven grade 1 glioma\u002Fmixed glio-neuronal tumors or pleomorphic xanthoastrocytoma (PXA) confirmed by local referee and the centrally pathology reviewing\n* Determination of a negative BRAFv600 mutation by immunohistochemistry and\u002For molecular methods\n* Systematic determination 7q34 duplication status or KIAA1549-BRAF fusion\n* Midline tumors without proven histone H3 mutations\n* Diffuse glioma without IDH1 mutation\n* Collection of fresh frozen tumor tissues and\u002For paraffin-embedded samples for further molecular biomarker testing\n* Sus-tentorial, optic pathway, midline and spine locations allowed\n* Karnofsky or Lansky ≥ 50%\n* 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.\n* Infants below one year of age with chiasmatic and\u002For hypothalamic tumor will be treated immediately after surgery, independently from neurological and\u002For visual evolution\n* 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.\n* Patients must have adequate bone marrow function defined as: absolute neutrophil count (ANC) ≥ 1500\u002FµL; platelets ≥ 100,000\u002FµL and hemoglobin ≥ 9.0 g\u002Fdl\n* 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\u002FPTT \\\u003C 1.5 x upper limit of normal,\n* Patients must have adequate renal function within 7 days prior to screening: serum creatinine \\\u003C 1.5 x upper limit of normal for age and a creatinine clearance \\> 60 ml\u002Fmin for 1.73 m2\n* Cardiac function defined as a corrected QT (QTcF) interval \\\u003C 480 msec, LVEF ≥ lower limit of normal (LLN) by echocardiogram (ECHO)\n* Adequate blood pressure control (smaller or equal to the 95th percentile for patient's age, height and gender)\n* Patients are willing and able to comply with scheduled visits, treatment plan, laboratory tests and study procedures\n* 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.\n\nNon-inclusion criteria\n\n* Patients presenting a neurofibromatosis type 1 (NF1) congenital disease\n* Pure optic nerve glioma, limited to one nerve and without optic chiasma infiltration.\n* Completely resected tumors\n* Previous treatment except tumor surgery\n* Pregnancy and lactation\n* Participation in other clinical trials\n* Prior non-surgical therapy for this tumor\n* Diffuse intrinsic pontine glioma (DIPG), even if histologically diagnosed as WHO grade II\n* Subependymal giant astrocytoma (SEGA) in patients with TSC\n* Patient having a known diagnosis of human immunodeficiency virus (HIV) infection, hepatitis B or C\n* Known hypersensitivity to drugs or excipients\n* History of another malignancy\n* History of current uncontrolled infection","1 Month","25 Years",{"count":104,"type":21},134,[106],"PHASE2","Pediatric low-grade glioma (PLGG) is a heterogeneous group of WHO grade I and II brain tumors, associated with a 10-year overall survival of 90%. It is the most common form of primary central nervous system (CNS) tumor arising during childhood, adolescence and young adulthood, accounting for over 30% of CNS tumors in this age group. A large group of PLGG patients will benefit from a complete resection of their tumor. Nevertheless, PLGG can occur anywhere and can be in some locations associated with neurological symptoms, unresectable or radiological progressive tumors that need medical treatments rapidly to avoid long-term sequelae. The current problem during this first line therapy is to improve tumor response, overall survival rate, as well as progression free survival. In our study, we will focus on a specific group of PLGGs without any congenital NF1 mutation and with a wild-type BRAF gene in the tumor. In this subgroup, for instance, the PFS is not increasing anymore above 50% at 3 years independently from the chemotherapeutic scheme. The two current standard therapies are carboplatin plus vincristine during 81 weeks or a weekly IV administration of vinblastine during 70 weeks. The most recent Canadian approach with vinblastine seems to have the same PFS rate, but with a better daily tolerance and less toxicities than the carboplatin\u002Fvincristine combination. Therefore, it is becoming the new standard approach in those patients. Nevertheless, we need to improve more their outcome with less recurs and a better first-line tumor response. The recent molecular discoveries involving the Ras\u002Fmitogen-activated protein kinase pathway in those PLGG is opening a new era with specific targeted therapies that might be the key to improve their survivals and giving hope to less treatment lines and a better tumor response. Therefore, we designed a prospective open randomized phase II study, named PLGG-MEKTRIC, comparing the experimental arm (a daily MEK inhibitor, Trametinib, Mekinist©) to a standard arm comprising weekly vinblastine during 18 courses of 4 weeks each. The study will enroll 134 patients with a PLGG during childhood, adolescence or young adulthood with no NF1-related disease and without any BRAFv600 mutation located in brain or spine. 67 patients, in each treatment arm, are planned to be enrolled to answer our primary objective. This primary objective will be to determine in the experimental arm a 20% superiority of the 3-year PFS rate in comparison with the standard treatment administered during 18 courses (e.g. 72 weeks). A stratification of the patients will be done in both arms based on molecular tumor results and brain\u002Fspine locations to obtain two equivalent arms to be analyzed.\n\nThe recruitment time will be 36 months and the complete follow-up of each patient will last 3 years. The secondary objectives will be in both arms: the tumor response rate at 24 and 72 weeks of treatment, the 3-year PFS and OS rates and the frequency of AE\u002FSAE\u002FSUSAR (Adverse Event\u002FSerious Adverse Event) based on CTCAE criteria during the 3 years after the first administration. A Quality of Life (QoL) assessment, based on PEDsQL questionnaires, at 24 weeks, at the end of treatment and 3 years after 1st treatment administration in both arms will be part of this study. Finally, 3-year PFS and OS will be analyzed according to molecular biomarkers and visual assessment (LogMar scale) in each arm. An economic analysis is also planned as an ancillary study to determine a cost effectiveness of the best arm and complementary ancillary molecular studies are already organized. In the future, we hope to push forward this new-targeted therapy as a referenced first line treatment of pediatric PLGG to obtain the best tolerance and positive long-term impact and to extend our knowledge of MEK inhibitor impact in molecular subgroups and in optical pathway locations. We also plan to do a \"switch\" strategy in patients relapsing in standard arm and we will propose systematically to those patients the experimental treatment (MEK inhibitor ).",[109,110,30],"Grade 1 Glioma","Mixed Glio-neuronal Tumors","2025-08-04",{"date":113,"type":38},"2025-08-08",{"date":115,"type":38},"2022-05-05",{"date":117,"type":21},"2031-12-01",{"name":119,"class":45},"University Hospital, Strasbourg, France",25]