[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"diffuse-midline-glioma-h3k27-altered\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:diffuse-midline-glioma-h3k27-altered":36},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,53],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":16,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":20,"targetDuration":4,"studyType":23,"phases":24,"briefSummary":26,"conditions":27,"keywords":37,"overallStatus":40,"whyStopped":4,"lastUpdateSubmitDate":41,"lastUpdatePostDateStruct":42,"startDateStruct":45,"completionDateStruct":47,"leadSponsor":49,"locationsCount":52},"100541748","early-phase-1-lorlatinib-for-newly-diagnosed-high-grade-glioma-with-ros-or-alk-fusion-100541748",false,"NCT06333899","Lorlatinib for Newly-Diagnosed High-Grade Glioma With ROS or ALK Fusion","A Pilot Study of Lorlatinib for Treatment of Children With Newly Diagnosed High-Grade Glioma With ROS-1 (ROS Proto-Oncogene 1, Receptor Tyrosine Kinase) or ALK (Anaplastic Lymphoma Kinase) Fusion","Inclusion Criteria:\n\n1. Patients must be ≥ 12 months and ≤ 21 years of age at the time of study enrollment on TarGeT-SCR.\n2. Diagnosis:\n\n   Patients with newly diagnosed high-grade glioma (HGG), including diffuse intrinsic pontine gliomas (DIPG), whose tumors harbor an ALK or ROS-1 fusion alteration are eligible. Patients must have had histologically verified high-grade glioma from diagnostic biopsy or resection. For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2\u002F3 of the pons, with histopathology consistent with diffuse WHO Grade 2-4. All other HGGs must be Grade 3 or 4.\n3. Disease Status:\n\n   Patients with disseminated DIPG or HGG are eligible only if the patient is to receive chemotherapy only, i.e. no craniospinal RT is intended to be given. MRI of spine must be performed if disseminated disease is suspected clinically by the treating physicians. Patients with primary spinal tumors are eligible only if the patient is to receive either chemotherapy or focal radiation therapy, i.e., no craniospinal RT is intended to be given. Patients with leptomeningeal disease only, with no definitive identifiable primary tumor, and documented ALK or ROS-1 fusion, must be discussed with the Study Chair on a case-by-case basis.\n4. Performance Level:\n\n   Karnofsky ≥ 50% for patients \\> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix I). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n5. Prior Therapy:\n\n   * Patients must not have received any prior anti-cancer chemotherapy.\n   * Prior use of corticosteroids is allowed (see below Exclusion Criteria)\n6. Organ Function Requirements 6.1 Adequate Bone Marrow Function Defined as:\n\n   * Peripheral absolute neutrophil count (ANC) ≥ 1000\u002FμL\n   * Platelet count ≥ 100,000\u002FμL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)\n   * Hemoglobin \\>8 g\u002FdL (may receive transfusions) 6.2 Adequate Renal Function Defined as:\n   * Serum creatinine within normal institutional limits OR Creatinine clearance or radioisotope GFR ≥ 70ml\u002Fmin\u002F1.73 m2 6.3 Adequate Liver Function Defined as:\n   * Total bilirubin ≤ 2 × institutional upper limit of normal\n   * AST(aspartate aminotransferase)\u002FALT(alanine transaminase) ≤ 2.5 × institutional upper limit of normal 6.4 Adequate Pulmonary Function Defined as: Pulse oximetry \\> 94% on room air if there is clinical indication for determination (e.g. dyspnea at rest).\n\n6.5Adequate Cardiac Function Defined as: QTc ≤ 470 msec (by Bazett formula) 6.6 Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled.\n\n6.7 Informed Consent: All patients and\u002For their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines\n\nExclusion Criteria:\n\n1. Pregnant or breast-feeding women will not be entered on this study due to unknown risks of fetal and teratogenic adverse events as seen in animal\u002Fhuman studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.\n\n   Females of reproductive potential must use an effective non-hormonal method of contraception, since lorlatinib can render hormonal contraceptives ineffective, during study treatment and for at least 6 months after the final dose. Males with female partners of reproductive potential must use effective contraception during treatment with lorlatinib and for 3 months after the final dose.\n2. Concomitant Medications\n\n   * Investigational Agents\u002FDrugs: Patients who have previously received or are currently receiving another investigational drug are not eligible.\n   * Anti-cancer Agents: Patients who have previously received or are currently receiving other anti-cancer agents, including chemotherapy, immunotherapy, monoclonal antibodies, biologic or targeted therapy, are not eligible\n3. Infection: Patients must not have any active, uncontrolled systemic bacterial, viral or fungal infection.\n4. Patients who have received prior solid organ transplantation are not eligible.\n5. Patients must not have malabsorption syndrome or other condition affecting oral absorption.\n6. Patients must not be receiving any treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor or inducer. Discontinue strong CYP3A inducers for 3 plasma half-lives of the strong CYP3A inducer prior to treatment with loraltinib. Moderate inducers of CYP3A4 should be avoided\n7. Avoid concomitant use of lorlatinib with certain CYP3A substrates, for which minimal concentration changes may lead to serious therapeutic failures. If concomitant use is unavoidable, increase the CYP3A substrate dosage in accordance with approved product labeling.\n8. P-glycoprotein (P-gp) substrates: Lorlatinib is considered a moderate P-gp inducer. Co-administration of lorlatinib with P-gp substrates including but not limited to digoxin should be avoided as the concentration of these drugs may be reduced by lorlatinib.\n9. Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.\n10. Patients with a known personal history of acute or chronic severe psychiatric disorders or current history of suicidal ideation and history of suicide attempt.",true,"ALL","1 Year","21 Years",{"count":21,"type":22},15,"ESTIMATED","INTERVENTIONAL",[25],"EARLY_PHASE1","The goal of this study is to determine the response of the study drug loratinib in treating children who are newly diagnosed high-grade glioma with a fusion in ALK or ROS1. It will also evaluate the safety of lorlatinib when given with chemotherapy or after radiation therapy.",[28,29,30,31,32,33,34,35,36],"High Grade Glioma","Diffuse Intrinsic Pontine Glioma","Anaplastic Astrocytoma","Infant Type Hemispheric Glioma","Glioblastoma","Glioblastoma Multiforme","WHO Grade III Glioma","WHO Grade IV Glioma","Diffuse Midline Glioma, H3K27-altered",[38,39,28,29],"ALK fusion","ROS fusion","RECRUITING","2026-06-25",{"date":43,"type":44},"2026-06-29","ACTUAL",{"date":46,"type":44},"2025-08-03",{"date":48,"type":22},"2035-06-01",{"name":50,"class":51},"Nationwide Children's Hospital","OTHER",18,{"id":54,"slug":55,"hasResults":11,"nctId":56,"briefTitle":57,"officialTitle":58,"acronym":59,"eligibilityCriteria":60,"healthyVolunteers":11,"sex":17,"minAge":61,"maxAge":4,"enrollmentInfo":62,"targetDuration":4,"studyType":23,"phases":64,"briefSummary":66,"conditions":67,"keywords":69,"overallStatus":40,"whyStopped":4,"lastUpdateSubmitDate":74,"lastUpdatePostDateStruct":75,"startDateStruct":77,"completionDateStruct":79,"leadSponsor":81,"locationsCount":83},"100475900","phase-3-biological-medicine-for-diffuse-intrinsic-pontine-glioma-dipg-eradication-20-100475900","NCT05476939","Biological Medicine for Diffuse Intrinsic Pontine Glioma (DIPG) Eradication 2.0","Biological Medicine for Diffuse Intrinsic Pontine Glioma (DIPG) Eradication","BIOMEDE 2","Eligibility criteria for the inclusion (registration) in BIOMEDE 2.0 study:\n\n* Diagnosis Criteria:\n\n  * Diagnosis of DIPG (clinical and radiological). As biopsy is not standard for these tumors, an informed consent is required for the necessary histological verification. \\[Biopsy-part of BIOMEDE 2.0 trial\\]. OR\n  * Histological diagnosis of DIPG (i.e. H3K28M or EZHIP positive Diffuse Midline Glioma located in the pons) in case the tumor biopsy was performed before study entry. The diagnosis will be defined by 1\u002F diffuse glioma, 2\u002F H3K28M mutation or loss of H3K28 trimethylation together with EZHIP overexpression. In this situation, patient will sign the consent after the diagnosis to allow central review and biomarkers assessment thereafter. OR\n  * Molecular diagnosis of DIPG (i.e. H3K28M) in case a liquid biopsy (CSF or blood) was performed before study entry, in a patient who could not undergo a tumor biopsy because it was too dangerous according to the patient's clinical condition. The diagnosis will be defined by 1\u002F DIPG, 2\u002F H3K28M mutation. In this situation, patient will sign the consent after the diagnosis to allow collection of the molecular report. OR\n  * Non-DIPG diffuse midline gliomas (ND-DMG), H3K28M mutant or with H3K28 trimethylation loss together with EZHIP overexpression, will be eligible for the trial after biopsy or surgery. As biopsy and surgery is considered as standard practice for these locations, informed consent for the biopsy will not be necessary. Patient will sign the consent after the diagnosis to allow central review and biomarkers assessment thereafter. OR\n  * Non-DIPG diffuse midline gliomas (ND-DMG) will be eligible for the trial before the biopsy in case the diagnosis is clinically or radiologically suspected. Informed consent for the biopsy and molecular analysis will be necessary. Then, if the central pathology review concludes to a ND-DMG with H3K28M mutant or H3K28 trimethylation loss together with EZHIP overexpression, these patients will be eligible for the treatment part of the trial.\n* Eligible for a biopsy, or biopsy material available for the biomarker assessment.\n* Age \\> 6 months, with no upper age limit. Children between 6 months and 3 years will be discussed on a case by case basis for inclusion in the study for the feasibility of the stereotactic biopsy.\n* Eligible for cerebral or craniospinal radiotherapy.\n* Tumor at diagnosis: no prior chemotherapy for the present cancer; no prior cerebral radiation therapy even for another neoplasm. Surgery is allowed when performed for diagnostic or therapeutic purpose.\n* Metastatic diseases or spinal tumors allowed; in this case, patients would receive craniospinal or spinal radiotherapy and medical treatment (everolimus or ONC201) will be postponed and only started after the end of radiotherapy.\n* Patients must be affiliated to a social security system or beneficiary of the same according to local requirements.\n* Written informed consent from parents\u002Flegal representative, patient, and age-appropriate assent before any study-specific procedures are conducted according to local, regional or national guidelines.\n\nNon eligibility criteria for the inclusion (registration) in BIOMEDE 2.0 study:\n\n* Uncontrolled spontaneous massive intratumor bleeding. Patients with post-operative bleeding will be allowed to enter the study provided the hemorrhage is controled. Same rule applies for the other post-operative complications (infection, CSF leakage, absence of wound closure, subdural collection…).\n* Any other concomitant anti-cancer treatment not foreseen by this protocol is not allowed, except corticosteroids and Bevacizumab which are allowed during the protocol. Bevacizumab is not allowed before and until 15 days after the surgery. The use of bevacizumab and corticosteroids will be taken into account when judging the possibility of progression\u002Fpseudoprogression.\n* Any other cancer diagnosed during the last 5 years.\n* Uncontrolled intercurrent illness or active infection.\n* Any other co-morbid condition that in the investigator's opinion would impair study participation.\n* Unable for medical follow-up (geographic, social or mental reasons).\n* Patient previously treated with irradiation on the brainstem for another neoplasm.\n* Participation in another clinical study with an investigational product while on study treatment.\n* Patient under guardianship or deprived of his\u002Fher liberty by a judicial or administrative decision or incapable of giving his\u002Fher consent.\n\nEligibility criteria for the randomization in BIOMEDE 2.0 study:\n\n* Patient enrolled in the BIOMEDE 2.0 study.\n* Life expectancy \\> 12 weeks after the start of study treatment.\n* Histological diagnosis of DIPG (as per the WHO criteria) confirmed by central pathology review, OR Typical radiology of a DIPG (mandatory central radiological review) as well as the short clinical history (less than three months of pre-existing symptoms) in case of suspected DIPG but no histological confirmation (tumor biopsy performed but not informative), or suspected DIPG with detection of H3K28M mutation in the CSF or blood (ctDNA analysis in the CSF or blood), OR Histological diagnosis of ND-DMG confirmed by central pathology review, with mutation in the histone H3.1, H3.2, H3.3 genes, or loss of H3K28me3 and EZHIP overexpression by immunohistochemistry.\n* Karnofsky performance status scale or Lansky Play Scale \\> 50%. The PS should not take the neurologic deficit per se into account. NB: Children and adults with a worse performance status due to glioma-related motor paresis can be included.\n* Highly effective and appropriate contraception for patients (male and female) of reproductive potential during their entire participation in the study and during 6 months after the end of treatment.\n* Negative pregnancy test (serum beta-HCG or urinary test) evaluated within one week prior randomization in sexually active females of reproductive potential.\n* Absolute neutrophil count \\> 1.0 x 10\\^9\u002Fl, Platelets \\> 100 x 10\\^9\u002Fl.\n* Total bilirubin \\\u003C 1.5 x ULN, AST and ALT\\\u003C 2.5 x ULN.\n* Serum creatinine \\\u003C 1.5 X ULN for age. If serum creatinine \\> 1.5 x ULN, creatinine clearance must be \\> 70 ml\u002Fmin\u002F1.73 m² (as per local practice).\n* Normal coagulation tests within the local reference ranges.\n* Written informed consent from parents\u002Flegal representative, patient, and age-appropriate assent before randomization according to local, regional or national guidelines.\n\nNon Eligibility criteria for the randomization in BIOMEDE 2.0 study:\n\n* Current organ toxicity \\> grade 2 according to the NCI-CTCAE version 5.0, especially cardiovascular or renal disease (including but not limited to: congenital long QT syndrome, nephrotic syndrome, glomerulopathy, uncontrolled high blood pressure despite adequate treatment).\n* Patients with the following cardiac history cannot take ONC201:\n\n  * Prolongation of QT\u002FQTcF interval (QTc interval \\> 480 milliseconds) preferably using Frederica's QT correction formula on two ECGs separated by at least 48 hours.\n  * A history of Torsades de pointes or heart failure, hypokalemia, or family history of prolonged QT Syndrome.\n  * Required concomitant use of medication(s) known to prolong the QT\u002FQTc interval.\n\nIn this case, patients will be treated in the Everolimus arm without randomization (except if contra-indication to Everolimus).\n\n* Pregnant or breastfeeding women.\n* Patients with chronic HBV disease compatible with the trial are not excluded from the study. These patients randomized to everolimus treatment will have regular viral load monitoring throughout the study.\n* Patients taking strong P450 inhibitors or inducers or PgP inhibitors are not excluded from the study but drug concentration of everolimus should be monitored carefully to avoid toxicity. Preferably alternative medications should be considered.\n* Patient with known congenital galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption will not be randomized and will be treated in the ONC201 arm (except if contra-indication to ONC201).\n* Patients with known hypersensitivity to any component of Everolimus (active substance, other rapamycin derivatives or excipients) will not be randomized and will be treated in the ONC201 arm (except if contra-indication to ONC201).\n* Patients with known hypersensitivity to any component of ONC201 (drug product or excipients) will not be randomized and will be treated in the Everolimus arm (except if contra-indication to Everolimus).","6 Months",{"count":63,"type":22},433,[65],"PHASE3","The BIOMEDE 2.0 study is the second stage of the BIOMEDE multi-arm, multistage rolling programme (adaptive platform protocol).\n\nIt is a multicenter, randomized, open-label, controlled phase-3 trial evaluating efficacy of ONC201 in comparison with everolimus (primary objective based on internal comparison) and subsequently to historical controls.\n\nTwo treatment groups will be compared. A switch between treatment groups is allowed after confirmation of the disease progression (real-time central review blinded to the treatment arm allocation). Study treatment will be continued until centrally confirmed disease progression (either radiologically or histologically), unacceptable toxicity or consent withdrawal.\n\nThe final conclusion of the trial will be successful for ONC201, if ONC201 is found significantly superior to everolimus in terms of centrally-reviewed PFS (Progression-free survival) from randomization (internal comparison) either overall, considering ND-DMG and DIPG-patients together, or in the subgroup of ND-DMG patients alone. In other cases, Everolimus will remain the standard arm unless it appears associated with an excess of toxicity compared to ONC201 which could then be discussed as a new standard.",[29,68,36],"Diffuse Midline Glioma, H3 K27M-Mutant",[70,71,72,73],"Children","Adolescents","Adults","Newly diagnosed","2026-02-03",{"date":76,"type":44},"2026-02-05",{"date":78,"type":44},"2022-09-29",{"date":80,"type":22},"2031-09",{"name":82,"class":51},"Gustave Roussy, Cancer Campus, Grand Paris",50]