[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"ependymoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:ependymoma":32},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,23,0,[8,57,87,152,188,211,241,267,299,323,352,384,413,445,488,529,567,589,616,639,665,687,708],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":20,"targetDuration":4,"studyType":23,"phases":24,"briefSummary":27,"conditions":28,"keywords":33,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":45,"lastUpdatePostDateStruct":46,"startDateStruct":49,"completionDateStruct":51,"leadSponsor":53,"locationsCount":56},"100565240","phase-1-pep-cmv--nivolumab-for-newly-diagnosed-diffuse-midline-gliomahigh-grade-glioma-and-recurrent-diffuse-midline-gliomahigh-grade-glioma-medulloblastoma-and-ependymoma-100565240",false,"NCT06639607","PEP-CMV + Nivolumab for Newly Diagnosed Diffuse Midline Glioma\u002FHigh-grade Glioma and Recurrent Diffuse Midline Glioma\u002FHigh-grade Glioma, Medulloblastoma, and Ependymoma","Phase 1\u002F2 Trial of PEP-CMV + Nivolumab for Newly Diagnosed Diffuse Midline Glioma\u002FHigh-grade Glioma and Recurrent Diffuse Midline Glioma\u002FHigh-grade Glioma, Medulloblastoma, and Ependymoma (PRiME II)","PRiME II","Inclusion Criteria for All Patients:\n\n* Patients must be ≥4 and ≤25 years of age (inclusive) at the time of study enrollment\n* Metastatic Disease: Patients with M+ disease are eligible.\n* Adequate bone marrow function defined as:\n\n  * ANC (Absolute neutrophil count) ≥ 1000\u002Fµl.\n  * Platelets ≥ 75,000\u002Fµl.\n  * Hemoglobin \\> 8 g\u002FdL. (may be supported)\n* Adequate renal function defined as:\n\n  * Creatinine clearance or radioisotope GFR ≥ 70ml\u002Fmin\u002F1.73 m\\^2 OR A serum creatinine based on age\u002Fgender as listed in the protocol. Note: The threshold creatinine values in this table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the CDC.\n* Adequate liver function defined as:\n\n  * Total bilirubin ≤1.5 times institutional ULN\n  * AST(SGOT) ≤3 × institutional upper limit of normal\n  * ALT(SGPT) ≤3 × institutional upper limit of normal\n* The effects of PEP-CMV and nivolumab on the developing human fetus are unknown. For this reason, female participants of childbearing potential and male participants who are sexually active must agree to use adequate contraception prior to study entry, for the duration of study participation, and for at least 6 months after completion of study participation. Pregnancy tests must be obtained in girls and women who are post-menarchal at screening, at least 24 hours prior to the first dose of nivolumab and every 4 weeks (+\u002F- 1 week) regardless of dosing schedule. An extension up to 72 hours prior to the start of study treatment is permissible in situations where results cannot be obtained within the standard 24 hour window. Should a female participant become pregnant or suspect she is pregnant while participating in this study, or should a male participant suspect he has fathered a child, s\u002Fhe must inform the treating physician immediately.\n* Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants. All patients and\u002For their parents or legal guardians must sign an IRB approved written informed consent document.\n\nInclusion Criteria for Patients with Newly-Diagnosed High-Grade Gliomas (HGG) and Newly-Diagnosed (DMG) (Stratum I):\n\n* Stratum I patients must have histologically confirmed, newly-diagnosed HGG (such as anaplastic astrocytoma, glioblastoma) or newly-diagnosed DMG (such H3K27M mutant diffuse midline glioma).\n\n  * Patients with a newly-diagnosed HGG\u002FDMG must enroll within 6 weeks of their final dose of standard radiation therapy with or without chemotherapy.\n  * Patients with primary spinal cord tumors are eligible\n  * Patients with a radiographically typical diffuse intrinsic pontine glioma (DIPG), a subset of DMG, defined as a tumor with a pontine epicenter and diffuse involvement of more than 2\u002F3 of the pons, are eligible without histologic confirmation.\n  * Patients with brainstem lesions that do not meet these radiographic criteria will be eligible if there is histologic confirmation of an infiltrating astrocytoma WHO grades II-IV (excluding grade II BRAF altered gliomas).\n* Karnofsky \\>50 for patients \\> 16 years of age or Lansky \\>50 for patients \\\u003C16 years of age. 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.\n* Patients must have adequate neurologic function defined as:\n\n  * Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment.\n* Patients must have received no prior therapy other than surgery, radiation, chemotherapy during radiotherapy and\u002For steroids (dexamethasone with goal to wean dexamethasone throughout protocol therapy), with the following qualifications:\n\n  * Patients with a newly diagnosed high-grade glioma or DMG must enroll within 42 days after their final dose of standard of care radiation therapy with or without chemotherapy.\n  * Patients with HGG or DMG are permitted, but not required, to have received chemotherapy during radiation. Bevacizumab is permitted prior to enrollment in patients with DMG or HGG. Patients must have received their last dose of bevacizumab at least 14 days prior to enrollment.\n  * For HGG patients, Patients must have received radiotherapy at a standard dose of \\~54 Gy in \\~1.8 Gy fractions for approximately 6 weeks with an acceptable variance of 10%. Radiation therapy must have begun no later than 30 days after the date of definitive surgery.\n  * For patients with DIPG, Patients must have received radiotherapy at a standard dose of radiotherapy of \\~54 Gy in \\~1.8 Gy daily fractions for approximately 6 weeks with an acceptable variance rate of 10%. Radiation therapy must have begun no later than 30 days after the date of radiographic diagnosis or biopsy.\n  * For patients with spinal cord HGG\u002FDMG: Patients must have received radiotherapy at a standard dose of \\~54 Gy in \\~1.8 Gy fractions for approximately 6-7 weeks with an acceptable variance rate of 10%.\n  * For patients with metastatic disease: Patients may have received standard dose craniospinal therapy.\n\nInclusion Criteria for patients with recurrent\u002Fprogressive HGG\u002FDMG (stratum II) or recurrent \u002Fprogressive MB or EPN (stratum III):\n\n* Recurrent MB, EPN, DMG or HGG: Patients must have a diagnosis of medulloblastoma that is recurrent, progressive or refractory. All patients must have histological verification of a MB, EPN, DMG or HGG at either original diagnosis or relapse.\n\n  * Patients must have adequate pretrial tumor material available (except DMG).\n  * Patients must have measurable disease defined as a lesion that can be measured in two perpendicular diameters on MRI.\n* Karnofsky ≥ 50% for patients \\>16 years of age or Lansky ≥ 50 for patients ≤ 16 years of age. 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.\n* Adequate neurologic function defined as:\n\n  * Patients with neurological deficits should have deficits that are stable for a minimum of 2 weeks prior to enrollment.\n  * Patients with current seizure disorders may be enrolled if seizures are well-controlled on antiepileptic therapies.\n* Previous enrollment and treatment on an interventional clinical trial(s) is allowed.\n* Patients must have received prior disease-directed therapy including radiotherapy for their initial diagnosis of MB, EPN, HGG, or DMG, unless the patient had a supratentorial EPN with GTR and radiation was not deemed necessary by the treating team.\n* Patients must have had their last fraction of:\n\n  * Craniospinal irradiation (if completed), total body irradiation or radiation to ≥ 50% of pelvis \\> 3 months prior to enrollment.\n  * Focal irradiation \\> 4 weeks prior to enrollment.\n* Patients must have received their last dose of myelosuppressive anticancer therapy at least 21 days prior to enrollment. Patients who have received nitrosoureas must have their last dose at least 42 days prior to enrollment.\n* Patients must have received their last dose of any immunotherapy agents at least 30 days prior to enrollment.\n* Patients must have received their last dose of non-myelosuppressive anticancer agents at least 7 days prior to study enrollment.\n* Patients must have received their last dose of any antibodies at least 21 days prior to enrollment.\n* Patients must have received their last dose of hematopoietic growth factors at least 14 days prior to enrollment for a long-acting growth factor (e.g. pegfilgrastim) or 7 days prior to enrollment for short-acting growth factor.\n* At least 90 days must have elapsed after an autologous stem cell infusion.\n\nExclusion Criteria - All Patients:\n\n* Pregnant or breast-feeding women will not be entered on this study due to known or unknown risks of fetal and teratogenic adverse events as seen in animal\u002Fhuman studies. Pregnancy tests must be obtained in girls and women who are post-menarchal at least 7 days prior to study enrollment. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.\n* Active infection requiring treatment.\n* Patients with malignancy related to HIV or solid organ transplant: known history of HIV, HBV surface antigen positivity or positive HCV antibody are not eligible. Viral testing is not required unless clinically indicated in patients without a known history\n* Known immunosuppressive disease.\n* Patients with active unrelated systemic illness including but not limited to renal, hepatic cardiac (congestive cardiac failure, myocardial infarction, myocarditis), or moderate to severe pulmonary problems generally defined by need for medical intervention (e.g., oxygen, medications) and\u002For limiting activities of daily living (generally CTCAE Grade 2 or higher) or shortness of breath with limited exertion are not eligible. Pulmonary conditions include (but are not limited to) COPD, asthma, and hemi-pneumectomy\n* Patients receiving concomitant immunosuppressive agents for medical conditions; inhaled corticosteroids for asthma are allowed.\n* Patients receiving concomitant tumor-directed therapy.\n* Patients receiving any other investigational drug therapy.\n* Previous enrollment and treatment on an interventional clinical trial (Stratum 1 only).\n* Patients on dexamethasone \\> 0.1 mg\u002FKg\u002Fday up to maximum dose of 4 mg\u002Fday or equivalent.\n* Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.\n* Patients at high risk for imminent neurologic decline due to extensive bulk disease, midline shift, or herniation on MRI. These patients should be discussed with the Study Chair.","ALL","4 Years","25 Years",{"count":21,"type":22},68,"ESTIMATED","INTERVENTIONAL",[25,26],"PHASE1","PHASE2","This is a multisite, phase I\u002FII clinical trial in children and young adults with newly-diagnosed high-grade glioma (HGG), diffuse midline glioma (DMG) and recurrent HGG\u002FDMG, Medulloblastoma (MB), or ependymoma (EPN) to determine the safety, immunogenicity, and efficacy of a CMV-directed peptide vaccine plus checkpoint blockade.",[29,30,31,32],"Diffuse Midline Glioma","Diffuse Midline High-grade Glioma","Medulloblastoma","Ependymoma",[34,35,36,37,38,39,40,41,42,43],"PEP-CMV","Peptide vaccine","Immunotherapy","Nivolumab","DIPG","Vaccine therapy","Pp65","Recurrent","Newly diagnosed","Diffuse intrinsic pontine glioma","RECRUITING","2026-06-15",{"date":47,"type":48},"2026-06-17","ACTUAL",{"date":50,"type":22},"2026-06-30",{"date":52,"type":22},"2051-06-30",{"name":54,"class":55},"Washington University School of Medicine","OTHER",3,{"id":58,"slug":59,"hasResults":11,"nctId":60,"briefTitle":61,"officialTitle":61,"acronym":62,"eligibilityCriteria":63,"healthyVolunteers":11,"sex":17,"minAge":64,"maxAge":65,"enrollmentInfo":66,"targetDuration":4,"studyType":23,"phases":68,"briefSummary":69,"conditions":70,"keywords":76,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":45,"lastUpdatePostDateStruct":79,"startDateStruct":80,"completionDateStruct":82,"leadSponsor":84,"locationsCount":86},"100530974","phase-1-immunotherapy-for-malignant-pediatric-brain-tumors-employing-adoptive-cellular-therapy-impact-100530974","NCT06193759","Immunotherapy for Malignant Pediatric Brain Tumors Employing Adoptive Cellular Therapy (IMPACT)","IMPACT","RECIPIENT SCREENING INCLUSION CRITERIA\n\n1. Diagnosis (select one group):\n\n   * Group A: New diagnosis of CNS embryonal tumors: medulloblastoma, embryonal tumor with multilayered rosettes, pineoblastoma, atypical teratoid\u002Frhabdoid tumor, and embryonal tumor, not otherwise specified (NOS).\n   * Group B: Radiographic evidence consistent with recurrent ependymoma, with planned or recent re-resection.\n2. Age:\n\n   * Group A: \\\u003C5 years of age at enrollment\n   * Group B: \\>1 year and \\\u003C30 years of age at enrollment\n3. Tissue:\n\n   o Group A: Availability of sufficient fresh or frozen tumor tissue (approximately 50 mg).\n\n   o Group B: Expectation of sufficient fresh or frozen tumor tissue, in the opinion of study PI or sub-I (based upon radiographic evidence of disease).\n4. Non-pregnant:\n\n   * Group A: N\u002FA\n   * Group B: For female of childbearing potential, must have negative pregnancy test.\n\n   Common to both groups:\n5. Karnofsky or Lansky score of ≥60%.\n6. Adequate organ function, defined below:\n\n   i. ANC ≥750\u002FµL. ii. Absolute lymphocyte count (ALC) \\>500\u002FμL. iii. Platelets ≥75K. iv. Bilirubin ≤3xULN. v. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) \\\u003C5x upper limit of normal (ULN).\n\n   vi. Serum creatinine ≤1.0 mg\u002FdL or 1.5x ULN for age (whichever is higher). vii. Pulse oximetry \\>90% on room air.\n7. The patient (if ≥18 years old), or the patient's parent(s)\u002Flegal guardian(s) (if the patient is a minor), is capable of providing informed consent.\n8. Patient deemed to be of sufficient size to undergo MNC apheresis for TSA-T generation (Groups A and B) and PBSC rescue (Group A only).\n9. Patient is a surgical candidate for placement of a Rickham reservoir in the opinion of study PI or medically licensed sub-I.\n\nRECIPIENT INCLUSION CRITERIA FOR PROCUREMENT\n\n1\\. Karnofsky or Lansky score of ≥60%. 2. Adequate organ function, defined below: i. ANC ≥750\u002FµL. ii. Absolute lymphocyte count (ALC) \\>500\u002FμL. iii. Platelets ≥75K. iv. Bilirubin ≤3xULN. v. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) \\\u003C5x upper limit of normal (ULN).\n\nvi. Serum creatinine ≤1.0mg\u002FdL or 1.5x ULN for age (whichever is higher). vii. Pulse oximetry \\>90% on room air. 3. Non-pregnant:\n\n* Group A: N\u002FA\n* Group B: For female of childbearing potential (if applicable), must have negative pregnancy test.\n\nRECIPIENT INCLUSION CRITERIA FOR INITIAL TSA-T ADMINISTRATION AND FOR ADDITIONAL INFUSIONS\n\n1. Applicable to TSA-T infusion #1 only: Group B participants must have histopathologic confirmation of recurrent ependymoma.\n2. Karnofsky or Lansky score of ≥60%.\n3. Adequate organ function, defined as below:\n\n   i. Bilirubin ≤3x ULN. ii. AST and ALT ≤5x ULN. iii. Serum creatinine ≤1.0mg\u002FdL or 1.5x ULN for age (whichever is higher). iv. Pulse oximetry \\>90% on room air.\n4. Applicable to TSA-T Infusion #1 only: Adequate count recovery, as described below, from prior therapies:\n\n   i. Absolute Neutrophil Count (ANC) \\>1000\u002FμL ii. Absolute Lymphocyte Count (ALC) \\>500\u002FμL\n5. Patients must have received their last dose of:\n\n   a. Myelosuppressive chemotherapy (if applicable) ≥14 days prior to TSA-T infusion b. Focal radiation (if applicable) ≥14 days prior to TSA-T infusion c. Craniospinal irradiation (if applicable) ≥28 days prior to TSA-T infusion\n6. Patients must have recovered from all acute effects of prior surgical intervention\u002Fs.\n7. Group B female of childbearing potential or male capable of fathering a child (if applicable): Agree to use contraceptive measures during TSA-T treatment participation through 6 months following last administration of TSA-Ts\n8. Group B female of childbearing potential (if applicable), must have negative pregnancy test.\n9. Neurologic status: Patient must have a stable neurologic exam for 2 weeks, on a stable or decreasing dose of steroids, prior to administration of the first dose of TSA-T cells, and stability for 1 week prior to all subsequent infusions. The exams demonstrating stability must be performed by the study team, although these may occur via telemedicine if necessary. Patient must agree to a brief (\\\u003C72 hours) course of steroids if the PI or medically-licensed sub-I deems it clinically necessary in the context of clinical deterioration.\n10. Presence of a Rickham reservoir and catheter for intracerebroventricular administration of TSA-T therapy, placed \\>7 days prior to TSA-T infusion.\n11. For patients with programmable VP shunts: Able to tolerate the shunt being closed for at least 4 hours, in the opinion of study PI or medically licensed sub-I.\n\nEXCLUSION CRITERIA RECIPIENT SCREENING EXCLUSION CRITERIA\n\n1\\. Patients with uncontrolled infections. 2. Patients with known HIV infection. 3. Group A patients with medulloblastoma of the SHH subtype.\n\nRECIPIENT EXCLUSION CRITERIA FOR PROCUREMENT\n\n1\\. Patients with a fever above 38.0°C. 2. Patients with known HIV infection. 3. Prior immunotherapy with an investigational agent within the 28 days prior to planned date of procurement collection for TSA-T manufacturing.\n\n4\\. Patients who will be unable to tolerate the apheresis procedure, including inability to tolerate placement of apheresis line (if applicable), in the opinion of PI or medically licensed sub-I.\n\n5\\. Patients who have overly bulky tumors on imaging are ineligible. These include the following: i. Tumor with any evidence of herniation or significant midline shift. ii. Tumor with a significant brainstem component. iii. Patients who are deemed to have overly bulky tumor by the PI of the study.\n\nIf, due to complications during apheresis or subsequent manufacturing, procurement is repeated at a later date using peripheral whole blood collection, exclusion criterion #4 does not apply.\n\nRECIPIENT EXCLUSION CRITERIA FOR INITIAL AND SUBSEQUENT TSA-T INFUSIONS\n\n1. Patients with progressive disease based on most recent evaluation (for subsequent infusions).\n\n   a. Patients with progressive disease based on most recent evaluation may receive initial TSA-T infusion but would be ineligible if the tumor is found to be progressive before subsequent infusions\n2. Patients with uncontrolled infections.\n3. Patients who have overly bulky tumors on imaging are ineligible. These include the following:\n\n   i. Tumor with any evidence of herniation or significant midline shift. ii. Tumor with a significant brainstem component. iii. Patients who are deemed to have overly bulky tumor by the PI of the study.\n4. Patients who received ATG, Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of TSA-T infusion.\n5. Patients receiving steroids (e.g., dexamethasone) at a dose of \\>0.05 mg\u002Fkg\u002Fday.\n6. Patients who have non-programmable VP shunts.","1 Year","30 Years",{"count":67,"type":22},12,[25],"This is an open-label phase 1 safety and feasibility study that will employ multi-tumor antigen specific cytotoxic T lymphocytes (TSA-T) directed against proteogenomically determined personalized tumor-specific antigens (TSA) derived from a patient's primary brain tumor tissues. Young patients with embryonal central nervous system (CNS) malignancies typically are unable to receive irradiation due to significant adverse effects and are treated with intensive chemotherapy followed by autologous stem cell rescue; however, despite intensive therapy, many of these patients relapse. In this study, individualized TSA-T cells will be generated against proteogenomically determined tumor-specific antigens after standard of care treatment in children less than 5 years of age with embryonal brain tumors. Correlative biological studies will measure clinical anti-tumor, immunological and biomarker effects.",[71,72,73,74,75,32],"Medulloblastoma, Childhood","Atypical Teratoid\u002FRhabdoid Tumor of CNS","Embryonal Tumor With Multilayered Rosettes","Pineoblastoma","Embryonal Brain Tumor Not Otherwise Specified",[77,78],"Cellular Therapy","Pediatric Brain Tumors",{"date":47,"type":48},{"date":81,"type":48},"2024-09-20",{"date":83,"type":22},"2032-12-29",{"name":85,"class":55},"Children's National Research Institute",1,{"id":88,"slug":89,"hasResults":11,"nctId":90,"briefTitle":91,"officialTitle":92,"acronym":93,"eligibilityCriteria":94,"healthyVolunteers":11,"sex":17,"minAge":95,"maxAge":4,"enrollmentInfo":96,"targetDuration":4,"studyType":23,"phases":98,"briefSummary":99,"conditions":100,"keywords":120,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":144,"lastUpdatePostDateStruct":145,"startDateStruct":147,"completionDateStruct":148,"leadSponsor":150,"locationsCount":86},"100562786","phase-1-study-in-children-and-adolescents-of-177lu-dotatate-lutathera-combined-with-the-parp-inhibitor-olaparib-for-the-treatment-of-recurrent-or-relapsed-solid-tumours-expressing-somatostatin-receptor-sstr-luparped-100562786","NCT06607692","Study in Children and Adolescents of 177Lu-DOTATATE (Lutathera®) Combined With the PARP Inhibitor Olaparib for the Treatment of Recurrent or Relapsed Solid Tumours Expressing Somatostatin Receptor (SSTR) (LuPARPed).","Single-arm Open-label Phase I\u002FII Study in Children and Adolescents of 177Lu-DOTATATE (Lutathera®) Combined With the PARP Inhibitor Olaparib for the Treatment of Recurrent or Relapsed Solid Tumours Expressing Somatostatin Receptor (SSTR) (LuPARPed).","LUPARPED","Inclusion criteria:\n\n* 18 months - 18 years of age at the time of the initial diagnosis.\n* ≥ 3 years at the moment of inclusion in the trial.\n* Diagnosis: relapsed\u002Frefractory solid tumours with positive uptake on SSTR-PET (PET-CT or PET-MRI), performed in the previous three months before entering the study.\n\nThe evaluation of SSTR expression will be classified according to a qualitative 4-point scale: SSTR expression V (visual score):\n\n* Score = 0: Below or equal to blood pool\n* Score = 1: Above blood pool and lower than liver\n* Score = 2: Equal to or above liver and lower than spleen\n* Score = 3: Equal to or above spleen\n\nPatients with scores ≥ 2 in the majority of the tumoral lesions will be considered to have a positive SSTR-PET and will be therefore eligible for the trial. Patients with a higher score are presumed to have a better response to the treatment.\n\nIt is admissible to have non-measurable disease only (e.g., HR-NB with bone-only or bone-marrow-only active disease).\n\n* Performance status ≥ 50% according to Lansky scale (\\\u003C16 years old) or Karnofsky scale (for ≥16 years old).\n* Life expectancy of at least 3 months.\n* Availability of ability to swallow tablets or capsules.\n* Adequate organ function within 28 days prior to enrolment, as defined by:\n\n  * Hb ≥10 g\u002Fdl (packed red blood transfusion is acceptable up to 24 hours prior starting treatment);\n  * White blood cell (WBC) count ≥ 2500\u002FμL (equivalent to 2.5 x 109\u002FL)\n  * Absolute Neutrophil Count (ANC) ≥ 1000\u002Fμl;\n  * Platelets ≥ 100.000\u002Fμl, without transfusion in the prior ≥7 days;\n  * Serum plasma creatinine ≤ 1.5 x upper limit of normal (ULN) OR estimated glomerular filtration rate (eGFR) ≥ 60 mL\u002Fmin\u002F1.73m2 (assessed by 2009-Schwartz formula).\n  * Total bilirubin ≤ 1.5 x the institutional ULN. For patients with known Gilbert's Syndrome ≤ 3.0 ULN is permitted.\n  * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 3.0 ULN.\n  * Albumin \\>3.0 g\u002FdL (3.0 g\u002FdL is equivalent to 30 g\u002FL)\n* A negative serum or urine pregnancy test in women with onset of menses or ≥12 years of age.\n* Patients of reproductive potential must agree to use highly effective contraceptive methods for the entire study duration and up to 7 months, in case of females, and 4 months in case of males, after the last dose of Lutathera, or up to 6 months, in case of females, and 3 months in case of males, after the last dose of olaparib, whichever takes places later.\n* Have the ability to comprehend and willingness to provide written informed consent (ICF) for the study before patient registration or any trial-related screening procedures. If the patient is \\\u003C18 years old, the written informed consent must be signed by the parent(s) or legal guardian(s) according to national regulations. In the case of patients between 12 and 17 years, they must sign an assent form, and if the patient turns 18 during their participation in the study, they must sign an informed consent form.\n* Adequate recovery from major surgery prior to receiving study treatment.\n* Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.\n\nExclusion criteria\n\n* Previous significant drug-induced hepatitis toxicity experienced in the past that has required treatment dose reductions, treatment discontinuation or that, at the investigator discretion, could infer a risk.\n* Having received more than one previous treatment with other radiolabelled somatostatin analogues.\n* Inability to swallow tablets or capsules.\n* Subjects who are currently receiving any other anticancer and\u002For investigational agents (e.g. chemotherapy, immunotherapy or biological therapy \\[including monoclonal antibodies\\]). There must be at least 28 days of washout from any prior treatment. In case of checkpoints inhibitors, there should be at least 4 months of washout. Palliative Radiation Therapy for symptom control (e.g. pain relief) could be acceptable, at the discretion of the investigator.\n* Treatment with long-acting somatostatin analogues within 28 days prior the administration of 177Lu-DOTATATE.\n* Known hypersensitivity to any of the excipients.\n* Subjects who have an uncontrolled infection.\n* Lactating women.","3 Years",{"count":97,"type":22},25,[25,26],"Study in children and adolescents of 177Lu DOTATATE (Lutathera®) combined with the PARP inhibitor olaparib for treatment of recurrent or relapsed solid tumours expressing somatostatin receptors (SSTR) (LuPARPed)",[101,31,102,103,104,105,106,107,108,38,109,110,111,112,113,114,115,116,117,118,32,119],"Solid Tumor Cancer","High Risk Neuroblastoma","High Grade Gliomas","Meningioma","Paraganglioma","Pheochromocytoma","Neuroendocrine Tumours (NET)","Adrenal Tumours","Glioblastoma","Glioblastoma (GBM)","Osteosarcoma Recurrent","Carcinoma Adrenal","Synovial Sarcomas","Esthesioneuroblastoma","Neuroblastoma Recurrent","Solid Tumor Refractory to Conventional Treatment","Medulloblastoma Recurrent","Paraganglioma\u002F Phaeochromocytoma","Ependymoma Recurrent",[121,122,123,124,125,126,127,128,129,130,131,132,133,38,134,135,136,137,138,139,140,141,142,32,143],"solid tumours","somatostatin receptors","SSTR","LUTETIUM","OLAPARIB","MEDULLOBLASTOMA","NEUROBLASTOMA","HIGH GRADE GLIOMA","MEININGIOMA","PARAGANGLIOMA","PHEOCHROMOCYTOMA","NEUROENDOCRINE TUMOURS","ADRENAL TUMOR","GLIOBLASTOMA","OSTEOSARCOMA","CARCINOMA ADRENAL","SYNOVIAL SARCOMA","ESTHESIONEUROBLASTOMA","RECURRENT","RELAPSED","RELAPSE","REFRACTORY","Ependimoma Recurrent","2026-06-02",{"date":146,"type":48},"2026-06-04",{"date":81,"type":48},{"date":149,"type":22},"2029-12",{"name":151,"class":55},"Fundación de investigación HM",{"id":153,"slug":154,"hasResults":11,"nctId":155,"briefTitle":156,"officialTitle":157,"acronym":158,"eligibilityCriteria":159,"healthyVolunteers":11,"sex":17,"minAge":64,"maxAge":19,"enrollmentInfo":160,"targetDuration":4,"studyType":23,"phases":162,"briefSummary":163,"conditions":164,"keywords":171,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":178,"lastUpdatePostDateStruct":179,"startDateStruct":181,"completionDateStruct":183,"leadSponsor":185,"locationsCount":187},"100625550","phase-2-intratumoral-dnx-2401-for-high-grade-pediatric-brain-tumors-100625550","NCT07424092","Intratumoral DNX-2401 for High Grade Pediatric Brain Tumors","Intratumoral DNX-2401 Administration for Recurrent and Refractory High Grade Brain Tumors in Pediatric and Young Adult Patients","PED-DNX2401","Inclusion Criteria:\n\n* The participant or participant's parents or legally acceptable representatives (if applicable) provides written informed consent for the trial and the pediatric participant provides writ-ten assent, where applicable, based on age and country requirements.\n* Patients with recurrent or refractory high grade malignant brain tumors (high grade glioma, embryonal CNS tumors \\[medulloblastomas, ATRT, EMTR, pineoblastoma\\], and ependymomas) diagnosis based on initial histopathological diagnosis and further clinical and radiological fol-low-up, in whom gross total resection is not feasible, and with a life expectancy of at least 16 weeks at the time of consent.\n* Recurrences within the radiation field will be considered if there is confirmed growth of the lesion in two consecutive MRI or if they occur at least 12 weeks after completion of ra-diation therapy, or if there is clear histopathological confirmation of tumor recurrence.\n* Male and female participants age ≥ 1 years and ≤ 25 years.\n* A single measurable lesion longer than 10 mm in two perpendicular diameters, considered by the investigator to be accessible for safe stereotactic biopsy and virus injection.\n* Lansky Performance Status (LPS) ≥ 60 for participants \\\u003C 16 years, or Karnofsky Performance Status (KPS) ≥ 60 for participants ≥ 16 years.\n* No other chemotherapy or immunotherapy in the 4 weeks before inclusion.\n* Steroids: free off or requiring decreasing or stable corticosteroid dose (≥ 0.05 mg\u002Fkg dexa-methasone daily, or equivalent for other steroids) in the 2 weeks before DNX-2401 admin-istration.\n* Radiation: no craniospinal irradiation, total body irradiation nor focal irradiation in the 6 weeks before inclusion.\n* Autologous Stem Cell Transplantation: patients must be ≥ 3 months post-transplant prior to entry of the study.\n* Patients must be fully recovered from all acute treatment related toxicities of all prior therapies.\n* Laboratory test: adequate hematological (platelets ≥ 100x10e9\u002FL, neutrophils ≥ 1.0x10e9\u002FL, hemoglobin ≥ 5,6 mmol\u002FL), renal function (creatinine \\\u003C1.5 times ULN) and liver function (≤3 times ULN) values.\n* Negative pregnancy test for female participants of child-bearing potential, where child-bearing potential is defined as a fertile female who is pubertal or post-pubertal and not permanently sterile (hysterectomy, bilateral salpingectomy, bilateral oophorectomy).\n* Female participants of child-bearing potential, who are sexually active, agree to use ac-ceptable birth control starting at informed consent and continuing for at least 120 days af-ter DNX-2401 administration. Male participants agree to use acceptable birth control start-ing at informed consent and continuing for at least 90 days after DNX-2401 administration.\n\nExclusion Criteria:\n\n* Any medical or psychological condition or disease that might interfere with the subject's ability to participate or give informed consent (if older than 16 years).\n* Spinal location, or lesions considered risky for stereotactic injection of virus or that might favor entrance of the virus in the ventricular system.\n* Any treatment outside the allowable guidelines outlined in the inclusion criteria.\n* Severe acute infection or intercurrent medical condition including, but not limited to se-vere renal, hepatic, heart or bone marrow failure that based on investigator discretion do not permit inclusion in the study.\n* Subjects with immunodeficiency or autoimmune conditions, active hepatitis or known HIV. No testing for Hepatitis B, Hepatitis C and HIV is required unless mandated by local health authority.\n* Subjects with another primary malignancy.\n* Prior history of encephalitis, multiple sclerosis or other CNS infections or primary CNS dis-ease that would interfere with evaluation.\n* Li Fraumeni Syndrome or a known germ line deficit in the retinoblastoma gene or its relat-ed pathways.\n* Concurrent therapy with any antiviral drug or any immunosuppressive drug (except ster-oids).\n* Life or life-attenuated vaccinations within 30 days prior to DNX-2401 administration and while participating in the study. Killed vaccines are permitted.\n* Prior participant in experimental viral therapy.\n* Inability to undergo MRI scans for any reason.\n* Pregnancy or breastfeeding.",{"count":161,"type":22},39,[26],"The goal of this clinical trial is to learn if intratumoral administration of DNX-2401 works to treat recurrent and refractory high grade brain tumors in children and young adults. It will also learn about the safety of DNX-2401.\n\nThe main questions it aims to answer are:\n\n* Does a single intratumoral administration of DNX-2401 elicit tumor response and improve survival?\n* Is a single intratumoral administration of DNX-2401 safe and well tolerated?\n\nParticipants will:\n\n* Undergo surgery for tumor biopsy followed by a single intratumoral administration of DNX-2401\n* Visit the clinic periodically for checkups and tests",[165,32,166,167,168,169,170],"High Grade Glioma","Embryonal Tumor of Brain","Recurrence","Refractory","Pediatric","Young Adult",[172,165,32,173,174,175,176,177],"High Grade Brain Tumors","Embryonal CNS Tumors","Recurrent or refractory","Pediatric and young adult patients","Oncolytic virus","DNX-2401","2026-05-21",{"date":180,"type":48},"2026-05-27",{"date":182,"type":48},"2026-05-12",{"date":184,"type":22},"2029-05",{"name":186,"class":55},"Clinica Universidad de Navarra, Universidad de Navarra",2,{"id":189,"slug":190,"hasResults":11,"nctId":191,"briefTitle":192,"officialTitle":193,"acronym":4,"eligibilityCriteria":194,"healthyVolunteers":11,"sex":17,"minAge":4,"maxAge":195,"enrollmentInfo":196,"targetDuration":4,"studyType":23,"phases":198,"briefSummary":199,"conditions":200,"keywords":4,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":202,"lastUpdatePostDateStruct":203,"startDateStruct":205,"completionDateStruct":207,"leadSponsor":209,"locationsCount":187},"100343351","phase-1-let-optimized-impt-in-treating-pediatric-patients-with-ependymoma-100343351","NCT03750513","LET Optimized IMPT in Treating Pediatric Patients With Ependymoma","Pilot Trial of LET Optimized IMPT for Pediatric Patients With Ependymoma","Inclusion Criteria:\n\n* Previous pathologic confirmation of ependymoma, World Health Organization (WHO) grade II or III\n* Disease must be confined to the brain (no evidence of spread on MR imaging of the spine or on staging lumbar puncture)\n* Patient may not receive chemotherapy concurrent with radiation\n* Signed informed consent by patient and\u002For parents or legal guardian\n* Lansky performance status score of 50 -100\n\nExclusion Criteria:\n\n* Patients with previous radiation therapy to the brain\n* Ependymoma of the spine\n* Disseminated ependymoma requiring craniospinal radiation therapy\n* Pregnancy\n* Inability to undergo MR imaging\n* Inability to receive gadolinium-based contrast agent","22 Years",{"count":197,"type":22},48,[25],"This phase I trial studies the side effects of linear energy transfer (LET) optimized image modulated proton therapy (IMPT) in treating pediatric patients with ependymoma. Radiation therapy such as LET optimized IMPT, uses proton beams to kill tumor cells and shrink tumors without damaging surrounding normal tissues.",[201,32],"Anaplastic Ependymoma","2026-05-18",{"date":204,"type":48},"2026-05-20",{"date":206,"type":48},"2019-04-01",{"date":208,"type":22},"2027-12-31",{"name":210,"class":55},"M.D. Anderson Cancer Center",{"id":212,"slug":213,"hasResults":11,"nctId":214,"briefTitle":215,"officialTitle":216,"acronym":4,"eligibilityCriteria":217,"healthyVolunteers":11,"sex":17,"minAge":218,"maxAge":219,"enrollmentInfo":220,"targetDuration":4,"studyType":23,"phases":222,"briefSummary":223,"conditions":224,"keywords":226,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":182,"lastUpdatePostDateStruct":232,"startDateStruct":234,"completionDateStruct":236,"leadSponsor":238,"locationsCount":86},"100528495","phase-1-plx038-in-primary-central-nervous-system-tumors-containing-myc-or-mycn-amplifications-100528495","NCT06161519","PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications","Phase I\u002FII Trial of PLX038 in Primary Central Nervous System Tumors With and Without MYC or MYCN Amplifications","* INCLUSION CRITERIA:\n* Participants must have documented pathologic diagnosis of confirmed primary central nervous system (CNS) tumor with one of the below diagnoses:\n\n  * Cohort Phase I: Any recurrent or progressive primary CNS tumor, regardless of molecular features.\n  * Cohort Phase IIA: Newly diagnosed MYCN amplified ependymoma after surgery and radiation.\n  * Cohort Phase IIB:\n\n    * Recurrent or progressive MYCN amplified ependymoma, OR\n    * Recurrent or progressive medulloblastoma with MYC or MYCN amplifications\n  * Cohort Phase IIC: Any other recurrent or progressive primary CNS tumor with MYC or MYCN amplifications.\n  * Cohort Phase IID: Any recurrent glioblastoma without MYC or MYCN amplifications.\n\nNOTE 1: Recurrence or progression may involve CNS, extra CNS, or both.\n\nNOTE 2: The presence of MYCN or MYC amplification will be determined by NSR device (via next-generation sequencing panel TruSight(TM) Oncology 500) and the threshold of MYCN or MYC amplification for eligibility purposes is a fold change (FC) of \\>= 2.5X (5 copies) with a minimum tumor content of 20%.\n\n* Participants must have archival tumor tissue (either a block or 15 formalin-fixed paraffin-embedded (FFPE) unstained slides) available for NCI LP review of MYC or MYCN amplification status and for correlative studies:\n\n  * Cohorts Phase I, Phase IIB, Phase IIC, and Phase IID: tumor tissue obtained at any point before trial treatment initiation, but preferably from most recent surgical resection before study treatment initiation.\n  * Cohort Phase IIA: tumor tissue obtained at original diagnosis.\n* Participants in Cohort Phase IIA must have completed surgery followed by radiation at least 4 weeks and no more than 10 weeks from the last dose of radiation prior to study treatment initiation.\n* Participants in Cohorts Phase I, Phase IIB, Phase IIC, and Phase IID must have completed prior cytotoxic chemotherapy or radiation at least 4 weeks prior to study treatment initiation (at least 6 weeks if the last regimen included lomustine (CCNU) or carmustine (BCNU); at least 3 weeks if the last regimen included bevacizumab; at least 4 weeks if the last regimen included a checkpoint inhibitor or any other type of immunotherapy or cellular therapy; at least 5 half-lives if the last regimen included any investigational agent(s). Participants previously treated with PHOTON radiation to at least 2 segments of the spine must have completed radiation at least 12 months before study treatment initiation.\n* Age \\>= 18 years.\n* Karnofsky \\>= 70%. NOTE: Participants with severe paraparesis\u002Fparaplegia who need minimal assistance for self-care due to their motor deficit but are otherwise functionally independent will be eligible.\n* Participants must have adequate organ and marrow function as defined below:\n\n  * leukocytes \\>=3,000\u002Fmicroliter\n  * absolute neutrophil count \\>1,500\u002Fmicroliter\n  * platelets \\>100,000\u002Fmicroliter\n  * hemoglobin \\>= 9 g\u002F dL (may be transfused within 2 weeks prior to treatment to achieve this level)\n  * total bilirubin within normal institutional limits\n  * aspartate aminotransferase (AST) \u002F alanine aminotransferase (ALT) \\\u003C2.5 X institutional upper limit of normal (ULN)\n  * creatinine within normal institutional limits OR\n  * estimated glomerular filtrate rate (eGFR) using chronic kidney disease epidemiology collaboration) (CKD-EPI) equation:\\>= 60 mL\u002Fmin\u002F1.73 m\\^2 for participants with creatinine levels above institutional normal\n* Women of child-bearing potential (WOCBP) and those who can father children must agree to use effective contraception (barrier, hormonal contraception, intrauterine device (IUD), surgical sterilization, barrier at the study entry, for the duration of study treatment and up to 6 months (WOCBP) and 3 months (those who can father children) after the last dose of study treatment.\n* Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 6 months after the last dose of the study drug.\n* Ability to self-report symptoms and physical function as determined by assessment of the clinical team performed at screening.\n* Participants must be able to understand and willing to sign a written informed consent document.\n\nEXCLUSION CRITERIA:\n\n* History of allergic reactions to compounds of similar chemical composition to PLX038.\n* Major surgery within 2 weeks prior to study treatment initiation. NOTE: The surgery is considered major if a mesenchymal barrier is opened (pleural cavity, peritoneum, meninges).\n* Participants who require treatment with strong inhibitors or inducers of CYP3A or with UGT1A1 inhibitors during the planned period of investigational treatment with PLX038. Lists including medications and substances known or with the potential to interact with CYP3A or UGT1A1 are provided in https:\u002F\u002Fdrug-interactions.medicine.iu.edu\u002Fmaintable.\n* History of treatment with pegylated topoisomerase inhibitors.\n* Has documented \\>= grade 2 PHOTON craniospinal irradiation (CSI) induced GI dysfunction.\n* Participants with history of homozygous for the UGT1A1\\*28 variant allele with severely reduced UGT1A1 activity.\n* Participants positive for Human immunodeficiency virus (HIV), Hepatitis C virus (HCV), and Hepatitis B virus (HBV).\n* Pregnancy (confirmed with beta human chorionic gonadotropin (beta-HCG) serum or urine pregnancy test performed in females of childbearing potential at screening).\n* Participants unable to have MRIs.\n* Prior or concurrent malignancy unless its natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen (https:\u002F\u002Fdeainfo.nci.nih.gov\u002Fadvisory\u002Fctac\u002F1117\u002F4-JournalClinicalOncology.pdf, https:\u002F\u002Fctep.cancer.gov\u002FprotocolDevelopment\u002Fdocs\u002FCTEP\\_Broadened\\_Eligibility\\_Criteria\\_Guidance.pdf)\n* Uncontrolled intercurrent illness evaluated by history, weight, and physical exam that would limit compliance with study requirements.","18 Years","120 Years",{"count":221,"type":22},146,[25,26],"Background:\n\nAbout 90,000 new cases of brain and spinal cord tumors are diagnosed annually in the United States. Most of these tumors are benign; however, about 30% are malignant, and 35% of people with malignant tumors in the brain and spinal cord will die within 5 years. Many of these people have changes in certain genes (MYC or MYCN) that drive the development of their cancers.\n\nObjective:\n\nTo test a study drug (PLX038) in people with tumors of the brain or spinal cord.\n\nEligibility:\n\nPeople aged 18 years or older with a tumor of the brain or spinal cord. Some participants must also have tumors with changes in the MYC or MYCN genes.\n\nDesign:\n\nParticipants will be screened. They will have a physical exam and blood tests. They will have imaging scans and a test of their heart function. They may need to have a biopsy: A sample of tissue will be removed from their tumor.\n\nPLX038 is given through a tube attached to a needle inserted into a vein in the arm. All participants will receive PLX038 on the first day of each 21-day treatment cycle. They will take a second drug 3 days later to help reduce the risk of infection; for this drug, participants will be shown how to inject themselves under the skin at home.\n\nBlood tests, imaging scans, and other tests will be repeated during study visits. Hair samples will also be collected during these visits. Some participants may have an additional biopsy.\n\nStudy treatment will continue up to 7 months.\n\nFollow-up visits will continue every few months for up to 5 years.",[225,31,32,109],"Glioma",[227,228,229,230,231],"Brain Tumors","Recurrent or progressive primary CNS tumors","Patient-Reported Outcomes","Spine Tumors","MYC or MYCN genes",{"date":233,"type":48},"2026-05-13",{"date":235,"type":48},"2024-01-31",{"date":237,"type":22},"2033-11-14",{"name":239,"class":240},"National Cancer Institute (NCI)","NIH",{"id":242,"slug":243,"hasResults":11,"nctId":244,"briefTitle":245,"officialTitle":246,"acronym":247,"eligibilityCriteria":248,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":218,"enrollmentInfo":249,"targetDuration":4,"studyType":251,"phases":4,"briefSummary":252,"conditions":253,"keywords":4,"overallStatus":257,"whyStopped":4,"lastUpdateSubmitDate":258,"lastUpdatePostDateStruct":259,"startDateStruct":261,"completionDateStruct":263,"leadSponsor":265,"locationsCount":4},"100639506","safety-and-efficacy-of-vertebral-body-sparing-craniospinal-irradiation-with-proton-therapy-in-pediatric-tumors-100639506","NCT07589361","Safety and Efficacy of Vertebral Body-Sparing Craniospinal Irradiation With Proton Therapy in Pediatric Tumors","Safety and Efficacy of Vertebral Body-Sparing Craniospinal Irradiation (VBS-CSI) With Proton Therapy in Pediatric Tumors: A Single-Center Prospective Observational Cohort Study","VBS-CSI-PT-PED","Inclusion Criteria:\n\n* The patient's legal guardian voluntarily signs the written informed consent form.\n* Age at diagnosis \\> 3 years and ≤ 18 years.\n* Histopathologically confirmed diagnosis of a central nervous system (CNS) tumor.\n* Indication for craniospinal irradiation (CSI) confirmed by multidisciplinary team (MDT) discussion.\n* Karnofsky Performance Score (KPS) ≥ 80.\n* For postoperative patients, complete healing of the surgical incision with no evidence of wound infection or other complications.\n* For women of childbearing potential, effective contraception must be used for at least one month prior to screening, and they must commit to continued contraception throughout the study period and for the required time after study completion.\n\nExclusion Criteria:\n\n* Previous receipt of any form of spinal radiotherapy.\n* Previous major spinal surgery for any reason.\n* Presence of clinically significant and confirmed spinal deformity at enrollment (e.g., Cobb angle \\> 10° measured by MRI or X-ray).\n* Presence of medical contraindications to proton radiotherapy.\n* Presence of any severe, uncontrolled systemic disease (e.g., active infection, severe cardiac, hepatic, renal, or respiratory insufficiency) that, in the investigator's judgment, makes the subject unsuitable for treatment under this protocol.\n* Female patients who are pregnant or breastfeeding.\n* Presence of any severe cognitive or psychiatric disorder that prevents understanding of or cooperation with study assessments.",{"count":250,"type":22},38,"OBSERVATIONAL","his is a single-center, prospective observational study in children and adolescents with central nervous system tumors who need whole-brain and whole-spine radiation therapy (craniospinal irradiation, CSI). The study uses proton therapy with a special vertebral body-sparing (VBS) technique to protect the front and center of the vertebrae, which helps preserve bone marrow function and growth. The main goals are to find safe dose limits for the vertebrae and check how often severe side effects occur. The study will also look at bone marrow preservation, spinal deformity, tumor control, survival, chemotherapy completion, neurocognitive function, quality of life, and growth and development for up to 5 years after treatment.",[254,31,255,32,256],"Pediatric Central Nervous System Tumors","Germinoma","Atypical Teratoid\u002FRhabdoid Tumor (AT\u002FRT)","NOT_YET_RECRUITING","2026-05-10",{"date":260,"type":48},"2026-05-15",{"date":262,"type":22},"2026-04-30",{"date":264,"type":22},"2033-12-31",{"name":266,"class":55},"Ruijin Hospital",{"id":268,"slug":269,"hasResults":11,"nctId":270,"briefTitle":271,"officialTitle":271,"acronym":272,"eligibilityCriteria":273,"healthyVolunteers":11,"sex":17,"minAge":274,"maxAge":4,"enrollmentInfo":275,"targetDuration":4,"studyType":23,"phases":277,"briefSummary":278,"conditions":279,"keywords":283,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":289,"lastUpdatePostDateStruct":290,"startDateStruct":292,"completionDateStruct":294,"leadSponsor":296,"locationsCount":298},"100391232","phase-2-innovative-trial-for-understanding-the-impact-of-targeted-therapies-in-nf2-related-schwannomatosis-intuitt-nf2-100391232","NCT04374305","Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2)","INTUITT-NF2","Eligibility Specific For MASTER PROTOCOL:\n\nInclusion Criteria:\n\n\\- Patients must have a pathogenic variant in the NF2 gene (either in the germline or in two NF2-related tumors) OR a confirmed diagnosis of NF2 by fulfilling National Institute of Health (NIH) criteria or Manchester criteria:\n\nThe NIH criteria includes presence of:\n\n* Bilateral vestibular schwannomas, OR\n* First-degree relative with NF2 and EITHER unilateral eighth nerve mass OR two of the following: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity.\n\nThe Manchester criteria includes presence of:\n\n* Bilateral vestibular schwannomas, OR\n* First-degree relative with NF2 and EITHER unilateral eighth nerve mass OR two of the following: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity, OR\n* Unilateral vestibular schwannoma AND any two of: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity, OR\n* Multiple meningiomas (two or more) AND unilateral vestibular schwannoma OR any two of: schwannoma, glioma, neurofibroma, cataract.\n\nSubjects must have a target NF2-related tumor (VS, non-VS, meningioma, or ependymoma) with documented radiographic progression within the preceding 36 months of Master Study registration defined as either:\n\n* at least 20% increase in volume of enhancing tumor\n* at least 2 mm increase in greatest linear dimension of enhancing tumor\n\nParticipants must have measurable disease, defined as:\n\n* VS, non-VS, or meningioma target lesions that can be accurately measured as at least 1 ml by volumetric MRI scan or in at least one dimension as ≥10 mm with conventional MRI scan. See protocol for the evaluation of measurable disease\n* Ependymoma target lesions measurable linearly.\n\nParticipant must have a target NF2-related tumor with the following qualities:\n\n* Not amenable to surgery due to patient refusal or due to high risk for surgical complications (e.g., damage to nerve function). Participant must be ≥ 12 years of age on Day 1 of treatment. Life expectancy of greater than 1 year Karnofsky performance status ≥ 70 or ECOG PS 0 or 1 (see Appendix A). Ability to understand and the willingness to sign written informed consent and assent documents.\n* Must have established relationship with primary care physician and provide contact information\n\nExclusion Criteria:\n\n* Participants who have had chemotherapy within a minimum of 4 weeks prior to Master Study registration (or a minimum of 5 half-lives and resolution to baseline of toxicities unless there are irreversible toxicities from prior drug that do not influence risk of next drug).\n* Participants who have received radiation to the target tumor within the last 3 years prior to Master study registration.\n* Participants who are receiving any other investigational agents.\n* Participants with target or non-target nervous system tumors that, in the opinion of the treating investigator, are likely to require active treatment (including surgery) within 6 months of registration to the Master Study.\n* History of a different malignancy, unless (a) have been disease-free for at least 2 years and are deemed by the treating investigator to be at low risk for recurrence of that malignancy.\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n* Pregnant women are excluded from this study because the experimental agents may have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these experimental agents, breastfeeding should be discontinued if the mother is treated.\n\nEligibility Criteria Specific to SUB-STUDY A (Brigatinib arm): CLOSED TO ENROLLMENT\n\nInclusion criteria\n\n* Participants must meet all eligibility criteria outlined in the Master Study\n* Participants must be willing and able to provide written informed consent\u002Fassent for the brigatinib arm of the INTUITT-NF2 trial.\n* Participant is ≥ 12 years of age and has body weight at least 40 kg on Day 1 of treatment.\n* Patient must be able to swallow pills.\n* Clinical laboratory values as specified below within 28 days before the first dose of study drug, as described in the protocol document:\n* Female patients participating in this study should avoid becoming pregnant, and male patients should avoid impregnating a female partner. Non-sterilized female patients of reproductive age group and male patients should use effective methods of contraception through defined periods during and after study treatment as specified below:\n\nFemale patients must meet 1 of the following:\n\n* Postmenopausal for at least 1 year before the screening visit, or\n* Surgically sterile, or\n* If they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing of the informed consent form through 4 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse. Brigatinib may decrease effectiveness of hormonal contraceptives, therefore, women are recommended to use non-hormonal methods of contraception. Highly effective non-hormonal birth control for women of child bearing potential with male partners includes:\n\n  * Sexual abstinence (no sexual intercourse)\n  * Intrauterine device (IUD) or intrauterine system (IUS)\n  * Bilateral tubal ligation (both tubes tied)\n  * Vasectomized partner\n\nMale patients, even if surgically sterilized (i.e., status post-vasectomy) must agree to 1 of the following:\n\n\\- Practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or completely abstain from heterosexual intercourse.\n\nExclusion criteria:\n\n* Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug (if applicable)\n* Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol\n* Treatment with any investigational products within 1 month or 5 half-lives (whichever is longer) before the first dose of study drug\n* Had major surgery within 30 days of the first dose of brigatinib. Minor surgical procedures such as catheter placement or minimally invasive biopsies are allowed.\n* Have significant, uncontrolled, or active cardiovascular disease (as outlined in the protocol):\n* Have uncontrolled hypertension (defined as an average systolic blood pressure \\>160 or an average diastolic blood pressure \\>100 for adults; for children: please refer to table in protocol\n\nEligibility Criteria Specific to SUB-STUDY B (Neratinib arm):\n\n* Participants must be willing and able to provide written informed consent\u002Fassent for the neratinib arm of the INTUITT-NF2 trial.\n* Participant must be ≥ 12 years of age and have body weight ≥ 40 kg on Day 1 of treatment.\n* Patient must be able to swallow pills.\n* Recovery (ie, to Grade 1 or baseline) from all clinically significant AEs related to prior therapies (excluding alopecia, neuropathy, and nail changes).\n* Clinical laboratory values as specified below within 14 days before the first dose of study drug:\n* ALT\u002Faspartate aminotransferase (AST) ≤ 2.5 × institutional upper limit of normal (ULN);\n* Total serum bilirubin ≤ 1.5 × institutional ULN (\\\u003C3.0 × institutional ULN for patients with Gilbert syndrome)\n* Estimated glomerular filtration rate (eGFR) ≥30 mL\u002Fmin\u002F1.73 m2, using the modification of diet in renal disease (MDRD) equation\n* Serum lipase ≤1.5 × institutional ULN\n* Absolute neutrophil count ≥1.5 × 109\u002FL\n* Platelet count ≥75 × 109\u002FL\n* Hemoglobin ≥9 g\u002FdL\n* Left ventricular ejection fraction (LVEF) ≥50% measured by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO).\n* It is not known what effects neratinib has on human pregnancy or development of the embryo or fetus. Therefore, female patients participating in this study should avoid becoming pregnant, and male patients should avoid impregnating a female partner. Non-sterilized female patients of reproductive age group and male patients should use effective methods of contraception through defined periods during and after study treatment as specified below:\n\nFemale patients must meet 1 of the following:\n\n* Postmenopausal for at least 1 year before the screening visit, or\n* Surgically sterile, or\n* If they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing of the informed consent form through 4 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse. Neratinib may decrease effectiveness of hormonal contraceptives, therefore, women are recommended to use non-hormonal methods of contraception. Highly effective non-hormonal birth control for women of child bearing potential with male partners includes:\n\n  * Sexual abstinence (no sexual intercourse)\n  * Intrauterine device (IUD) or intrauterine system (IUS)\n  * Bilateral tubal ligation (both tubes tied)\n  * Vasectomized partner\n\nMale patients, even if surgically sterilized (i.e., status post-vasectomy) must agree to 1 of the following:\n\n* Practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or completely abstain from heterosexual intercourse.\n* Female patients must have negative β-human chorionic gonadotropin (hCG) pregnancy test for premenopausal women of reproductive capacity (those who are biologically capable of having children) and for women less than 12 months after menopause. \\[Women are considered postmenopausal if they are ≥12 months without menses, in the absence of endocrine or anti-endocrine therapies.\\]\n\nExclusion Criteria\n\n* Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug (if applicable)\n* Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol\n* Treatment with any investigational products within 28 days or 5 half-lives (whichever is longer) before the first dose of study drug\n* Had major surgery within 30 days of the first dose of neratinib. Minor surgical procedures such as catheter placement or minimally invasive biopsies are allowed.\n* Have significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:\n* Myocardial infarction within 6 months before the first dose of neratinib.\n* Unstable angina within 6 months before first dose of neratinib.\n* Congestive heart failure within 6 months before first dose of neratinib.\n* History of clinically significant atrial arrhythmia (including clinically significant bradyarrhythmia), as determined by the treating physician.\n* Any history of clinically significant ventricular arrhythmia.\n* Had a cerebrovascular accident or transient ischemic attack within 6 months before first dose of neratinib.\n* QTc interval \\>0.450 seconds (males) or \\>0.470 (females), or known history of QTc prolongation or Torsade de Pointes (TdP)\n* Have a known history of HIV infection. Testing is not required in the absence of history.\n* Have malabsorption syndrome or other GI illness that could affect oral absorption of neratinib. Note: This includes any predisposing chronic condition resulting in baseline grade 2 or higher diarrhea\n* History of severe allergic reactions or intolerability attributed to compounds of similar chemical or biologic composition to neratinib.\n* Have any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere with the evaluation of neratinib.\n* Concurrent use of enzyme-inducing antiepileptic drugs (EIAEDs), including phenytoin, carbamazepine, oxcarbazepine, fosphenytoin, phenobarbital, pentobarbital, or primidone\n* Received systemic treatment with certain cytochrome P-450 inhibitors or inducers within 14 days before enrollment.\n\nEnrollment Criteria Specific to SUB-STUDY C (retifanlimab plus bevacizumab arm):\n\nInclusion Criteria\n\n* Participants must be willing and able to provide written informed consent\u002Fassent for the retifanlimab-bevacizumab arm of the INTUITT-NF2 trial.\n* Participants must have a target NF2-related tumor (VS, non-VS, meningioma, or ependymoma) with documented radiographic progression within the preceding 36-months.\n* Age between 12 and 25 years on day 1 of treatment.\n* Life expectancy of greater than 1 year.\n* Participants must meet the following organ and marrow function as defined below:\n\n  1. Leukocytes ≥3000\u002FmcL\n  2. Platelets ≥100,000\u002FmcL\n  3. Total Bilirubin ≤ 1.5 institutional upper limit of normal (ULN), (\\\u003C3.0 × institutional ULN for patients with Gilbert Syndrome)\n  4. AST(SGOT)\u002FALT(SGPT) ≤2.5 × institutional ULN\n  5. Urine Protein:Creatinine Ratio ≤ 1.9\n  6. Glomerular Filtration Rate (GFR) ≥30 mL\u002Fmin\u002F1.73 m2\n* Inhibition of the PD-1\u002FPD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death. Therefore, female patients participating in this study should avoid becoming pregnant, and male patients should avoid impregnating a female partner. Non-sterilized female patients of reproductive age group and male patients should use effective methods of contraception through defined periods during and after study treatment as specified below:\n\nFemale patients must meet 1 of the following:\n\n* Postmenopausal, defined as ≥12 consecutive months of amenorrhea in the absence of endocrine or anti-endocrine therapy, for a minimum of 1 year prior to screening visit, or\n* Surgically sterile, or\n* If they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing of the informed consent form through 4 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse. Highly effective non-hormonal birth control for women of childbearing potential with male partners may include:\n* Sexual abstinence (no sexual intercourse)\n* Intrauterine device (IUD) or intrauterine system (IUS)\n* Bilateral tubal ligation (both tubes tied)\n* Vasectomized partner Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to 1 of the following:\n* Practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or\n* Completely abstain from heterosexual intercourse.\n\nExclusion Criteria\n\n* History of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition to retifanlimab or bevacizumab\n* Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period prior to registration.\n* Treatment with any investigational products or chemotherapy within 28 days or 5 half-lives (whichever is longer) before the first dose of study drug.\n* Treatment with bevacizumab or any PD-1\u002FPD-L1 inhibitor within 180 days before the first dose of study drug.\n* Had major surgery within 30 days of the first dose of study drug. Minor surgical procedures such as catheter placement or minimally invasive biopsies are allowed.\n* Serious or non-healing wound, ulcer, or bone fracture.\n* History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to Day 1.\n* Imaging (CT or MRI) evidence of hemorrhage deemed significant by the treating physician (\\> grade 1). Subjects with significantly increased risk of CNS hemorrhage are not eligible.\n* Concurrent use of anti-coagulant drugs (not including prophylactic doses), history of coagulopathy, or evidence of bleeding diathesis or coagulopathy.\n* Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> Grade 1) with the exception of alopecia.\n* Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis.\n* Immune related toxicity during prior checkpoint inhibitor therapy for which permanent discontinuation of therapy was recommended (per product label or consensus guidelines) or any immune-related toxicity requiring intensive or prolonged immunosuppression to manage (with the exception of endocrinopathy that is well controlled on replacement hormones).\n* Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (\\> 10 mg\u002Fday of prednisone or equivalent).\n\n  1. Physiologic corticosteroid replacement therapy at doses ≤ 10 mg\u002Fday of prednisone or equivalent for adrenal or pituitary insufficiency and in the absence of active autoimmune disease is permitted.\n  2. Participants with asthma that requires intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections may participate.\n  3. Participants using topical, ocular, intra-articular, or intranasal corticosteroids (with minimal systemic absorption) may participate.\n  4. Brief courses of corticosteroids for prophylaxis (eg, contrast dye allergy) or study treatment-related standard premedications are permitted.\n* Active infections requiring systemic antibiotics or antifungal or antiviral treatment within 10 days before first dose of study treatment.\n* Has received a live vaccine within 28 days before the planned start of study treatment (with the exception of COVID-19 vaccines).\n\nNote: Examples of live vaccines include but are not limited to measles, mumps, rubella, varicella-zoster (chickenpox), yellow fever, rabies, BCG, and typhoid vaccines. Seasonal influenza vaccines for injection are generally killed-virus vaccines and are allowed; however, intranasal influenza vaccines are live, attenuated vaccines and are not allowed.\n\n* History of organ transplant, including allogeneic stem cell transplantation.\n* Clinically significant cardiovascular disease, such as:\n* Inadequately controlled HTN (defined as an average systolic blood pressure \\>160 or an average diastolic blood pressure \\> 100 for adult patients ≥ 21 years and as an average systolic BP \\> 130 or an average diastolic blood pressure \\>80 for pediatric patients 12-21 years) despite adequate treatment with medications. Patients with hypertension should be under treatment on study entry to control blood pressure.\n* History of CVA within 12 months of registration\n* Myocardial infarction or unstable angina within 12 months of registration\n* New York heart association grade II or greater congestive heart failure\n* Serious and inadequately controlled cardiac arrhythmia\n* Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection)\n* Clinically significant peripheral vascular disease","12 Years",{"count":276,"type":22},109,[26],"This is a multi-arm phase II platform-basket screening study designed to test multiple experimental therapies simultaneously in patients with NF2-related schwannomatosis (NF2-SWN, formerly known as neurofibromatosis type 2) with associated progressive tumors of vestibular schwannomas (VS), non-vestibular schwannomas (non-VS), meningiomas, and ependymomas.\n\nThis Master Study is being conducted as a \"basket\" study that may allow people with multiple tumor types associated with NF2-SWN to receive new drugs throughout this study. Embedded within the Master Study are individual drug substudies.\n\n* Investigational Drug Sub-study A: Brigatinib\n* Investigational Drug Sub-study B: Neratinib\n* Investigational Drug Sub-study C: Retifanlimab plus bevacizumab",[280,281,282,104,32],"Neurofibromatosis Type 2","Vestibular Schwannoma","Non-vestibular Schwannoma",[284,285,286,287,288],"neurofibromatosis type 2 (NF2)","vestibular schwannomas (VS)","non-vestibular schwannomas (non-VS)","meningioma","ependymoma","2026-05-04",{"date":291,"type":48},"2026-05-06",{"date":293,"type":48},"2020-06-20",{"date":295,"type":22},"2030-12-01",{"name":297,"class":55},"Scott R. Plotkin, MD, PhD",6,{"id":300,"slug":301,"hasResults":11,"nctId":302,"briefTitle":303,"officialTitle":304,"acronym":4,"eligibilityCriteria":305,"healthyVolunteers":11,"sex":17,"minAge":4,"maxAge":306,"enrollmentInfo":307,"targetDuration":4,"studyType":23,"phases":308,"briefSummary":309,"conditions":310,"keywords":4,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":314,"lastUpdatePostDateStruct":315,"startDateStruct":317,"completionDateStruct":319,"leadSponsor":321,"locationsCount":86},"100503471","phase-1-loc3car-locoregional-delivery-of-b7-h3-car-t-cells-for-pediatric-patients-with-primary-cns-tumors-100503471","NCT05835687","Loc3CAR: Locoregional Delivery of B7-H3-CAR T Cells for Pediatric Patients With Primary CNS Tumors","Loc3CAR: Locoregional Delivery of B7-H3-specific Chimeric Antigen Receptor Autologous T Cells for Pediatric Patients With Primary CNS Tumors","Inclusion Criteria: Screening Eligibility\n\n1. Age ≤ 21 years of age\n2. Primary CNS tumor\n3. For Cohort A, must have evidence of relapsed or refractory non-brainstem CNS tumor\n4. For Cohort B, must meet one of the following criteria:\n\n   * Adequate tumor tissue from primary tumor resection or biopsy for central pathology review (i.e., B7-H3 expression evaluation by immunohistochemistry \\[IHC\\] or H3K27M mutation if pontine lesion)\n   * Has a diagnosis of diffuse midline glioma that harbors a mutation associated with this entity (e.g. H3K27M)\n   * Has presumptive\u002Fsuspected brainstem high-grade neoplasm with available imaging for central imaging review\n5. Life expectancy of \\> 12 weeks\n6. Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines\n\nExclusion Criteria: Screening Eligibility All Participants\n\n1\\. Participant has other clinically significant medical disorders (e.g. serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that could compromise their ability to tolerate protocol therapy or would interfere with study procedure.\n\nInclusion Criteria: Procurement and T-cell Production Eligibility\n\n1. Age ≤ 21 years of age\n2. Primary CNS tumor with measurable or evaluable disease and meets criteria for either Cohort A or B:\n\n   * Cohort A: relapsed\u002Frefractory non-brainstem CNS primary tumor AND tumor is B7-H3 positive\n   * Cohort B: Diffuse midline glioma AND tumor is:\n\n     * B7-H3 positive if non-pontine\n     * OR H3K27-altered diffuse midline pontine glioma\n     * OR radiographically-confirmed classic\u002Ftypical DIPG\n3. Estimated life expectancy of \\>12 weeks\n4. Karnofsky or Lansky performance score ≥50\n5. Participant of childbearing\u002Fchild-fathering potential agrees to use contraception\n6. For females of childbearing age:\n\n   * Not pregnant with negative serum pregnancy test\n   * Not lactating with intent to breastfeed\n7. Chemotherapy\u002Fbiologic therapy must be discontinued ≥ 7 days prior to enrollment\n8. The last dose of antibody therapy (including check point inhibitor) must be at least 3 half-lives or 30 days, whichever is shorter, from the time of enrollment\n9. At least 30 days from most recent cell infusion prior to enrollment.\n10. All systemically administered corticosteroid therapy must be stable or decreasing for ≥1 week prior to enrollment, with a maximum dexamethasone dose of 2.8 mg\u002Fm\\^2\u002Fday\n11. Meets eligibility for apheresis, or has an apheresis product previously collected at a FACT-accredited program\n12. Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines\n\nExclusion Criteria: Procurement and T-cell Production Eligibility\n\n1. Known primary immunodeficiency or acquired immunodeficiency.\n2. Known HIV positivity\n3. Severe intercurrent bacterial, viral or fungal infection (e.g. active hepatitis B or C infection or adenovirus infection).\n4. Rapidly progressive disease\n5. Known underlying medical condition for which participation in this trial would not be in the best interest of the participant or that could prevent, limit or confound protocol assessments.\n6. Adult patient, Parent, or legal guardian is unwilling or unable to provide consent for participation in a 15 year long-term follow up study.\n\nInclusion Criteria: Treatment Eligibility\n\nCohort A\n\n* Relapsed\u002Frefractory non-brainstem CNS primary tumor\n* Tumor must be considered B7-H3 positive\n\nCohort B\n\n* Diffuse Midline Glioma - Must meet one of the following criteria\n\n  * Tumor is considered B7-H3 positive\n  * H3K27-altered diffuse midline pontine glioma\n  * Radiographically-confirmed classic\u002Ftypical DIPG\n* Must complete standard radiation prior to Loc3CAR treatment and be a minimum of 6 weeks post-completion of radiation therapy\n\nAll participants\n\n1. Age ≤ 21 years old\n2. Primary CNS tumor with measurable or evaluable disease\n3. Available autologous T-cell product that has met GMP release criteria\n4. Participant has a CNS reservoir catheter (e.g., Ommaya) or programmable shunt\n5. First CAR T cell infusion is planned\u002Fscheduled ≥ 5 days from CNS surgery, including catheter placement\n6. The following treatments must be discontinued for the specified duration prior to treatment enrollment:\n\n   * Radiation therapy: ≥ 6 weeks\n   * Bevacizumab: ≥ 28 days\n   * Cytotoxic chemotherapy: ≥ 21 days\n   * Biologic agents: ≥ 7 days\n   * Antibody therapy: ≥ 3 half-lives or 30 days (whichever is shorter)\n   * Cellular therapy: ≥ 30 days\n   * Investigational agent: ≥ 3 half-lives or 30 days (whichever is shorter)\n   * Corticosteroids: All systemically administered therapy must be stable or decreasing for ≥ 1 week prior to enrollment, with a maximum dexamethasone dose of 2.8 mg\u002Fm\\^2\u002Fday. Corticosteroid physiologic replacement therapy for management of pituitary\u002Fadrenal axis insufficiency and\u002For topical administration (e.g. inhaled or dermatologic) is allowed.\n7. Estimated life expectancy of \\>8 weeks\n8. Karnofsky or Lansky performance score ≥ 50\n9. Echocardiogram with a left ventricular ejection fraction ≥ 50%\n10. Adequate renal function defined as calculated creatinine clearance or radioisotope GFR ≥ 50 mL\u002Fmin\u002F1.73m\\^2.\n11. Adequate pulmonary function defined as forced vital capacity (FVC) ≥50% of predicted value or pulse oximetry ≥90% on room air.\n12. Total Bilirubin ≤3 times the upper limit of normal for age.\n13. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 times the upper limit of normal for age.\n14. Hemoglobin \\>8.0 g\u002FdL (can be transfused).\n15. Platelet count \\>50,000\u002Fmm\\^3 (can be transfused).\n16. Absolute neutrophil count (ANC) ≥1000\u002FuL.\n17. Taking anti-seizure medication, or agrees to initiate anti-seizure medication prior to starting study therapy.\n18. Has recovered from all NCI CTAE grade III-IV, non-hematologic acute toxicities from prior therapy.\n19. Male participants of child-fathering potential agree to use contraception\n20. Female participants of childbearing potential:\n\n    * Negative serum pregnancy test within 7 days prior to infusion\n    * Not lactating with intent to breastfeed\n    * If sexually active, agrees to use birth control until 3 months after T-cell infusion. Male partners should use a condom\n21. Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines\n\nExclusion Criteria: Treatment Eligibility-All Participants\n\n1. Participant has a non-programmable ventricular shunt that could compromise study therapy\n2. Participant has a reservoir catheter or shunt in a location that could compromise study therapy or patient safety\n3. Known primary immunodeficiency or acquired immunodeficiency.\n4. Known HIV positivity\n5. Severe intercurrent bacterial, viral or fungal infection\n6. Myocardial infarction, unstable angina, New York Heart Association class III and IV congestive heart failure, myocarditis, or ventricular arrhythmias requiring medication within 6 months prior to study entry\n7. Receiving therapy as outlined above during the 'wash-out' period\n8. Rapidly progressing disease\n9. Received any live vaccines within 30 days\n10. Known underlying medical condition for which participation in this trial would not be in the best interest of the participant or that could prevent, limit or confound protocol assessments\n11. Adult patient, Parent, or legal guardian is unwilling or unable to provide consent for participation in a 15 year long-term follow up study\n12. Evidence of uncontrolled hypertension. Anti-hypertensive medications are permitted if on a stable dose.\n13. Uncontrolled seizures","21 Years",{"count":197,"type":22},[25],"Loc3CAR is a Phase I clinical trial evaluating the use of autologous B7-H3-CAR T cells for participants ≤ 21 years old with primary CNS neoplasms. B7-H3-CAR T cells will be locoregionally administered via a CNS reservoir catheter. Study participants will be divided into two cohorts: cohort A with B7-H3-positive relapsed\u002Frefractory non-brainstem primary CNS tumors, and cohort B with diffuse midline gliomas (DMG). Participants will receive four (4) B7-H3-CAR T cell infusions over a 4 week period. The purpose of this study is to find the maximum (highest) dose of B7-H3-CAR T cells that are safe to give patients with primary brain tumors.\n\nPrimary objectives\n\n* To determine the safety, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for the locoregional delivery of autologous B7-H3-CAR T cells in patients ≤ 21 years of age with recurrent\u002Frefractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B).\n\nSecondary objectives\n\n* To assess the efficacy, defined as sustained objective response, a partial response (PR) or complete response (CR) observed anytime on active treatment with B7-H3-CAR T cells in patients with relapsed\u002Frefractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B).\n* To characterize and monitor neurologic toxicities in patients while on study (Cohort A and B).",[311,312,313,32,165,109,31],"Central Nervous System Neoplasms","Atypical Teratoid\u002FRhabdoid Tumor","Diffuse Midline Glioma, H3 K27M-Mutant","2026-05-01",{"date":316,"type":48},"2026-05-05",{"date":318,"type":48},"2023-04-27",{"date":320,"type":22},"2028-03",{"name":322,"class":55},"St. Jude Children's Research Hospital",{"id":324,"slug":325,"hasResults":11,"nctId":326,"briefTitle":327,"officialTitle":327,"acronym":328,"eligibilityCriteria":329,"healthyVolunteers":11,"sex":17,"minAge":218,"maxAge":4,"enrollmentInfo":330,"targetDuration":4,"studyType":23,"phases":332,"briefSummary":333,"conditions":334,"keywords":338,"overallStatus":257,"whyStopped":4,"lastUpdateSubmitDate":344,"lastUpdatePostDateStruct":345,"startDateStruct":346,"completionDateStruct":348,"leadSponsor":350,"locationsCount":56},"100577927","phase-2-pharmacoscopy-for-patients-with-refractory-primary-brain-tumors-100577927","NCT06804655","Pharmacoscopy for Patients With Refractory Primary Brain Tumors","EViDENCE-BT","Inclusion Criteria:\n\n1. Age 18 years or older on day of signing informed consent, female or male.\n2. Refractory glioblastoma, isocitrate dehydrogenase (IDH)-mutant astrocytoma or oligodendroglioma, histone-mutant glioma, ependymoma, medulloblastoma, meningioma or other rare primary brain tumor with a histological confirmation according to the WHO classification 2021. Primary tumors can be located at the cerebral or spinal level. Primary brain tumors with metastases outside of the brain may also be considered.\n3. Karnofsky performance status of 60 or more\n4. Life expectancy \\>12 weeks.\n5. Limited systemic therapeutic options as per treating physician judgement. The number of previous lines of therapies is not limited.\n6. Surgery clinically indicated. A histological confirmation of the diagnosis of a recurrent brain tumor will be required before any treatment can be initiated.\n7. Adequate bone marrow, renal and hepatic function\n8. Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and return for the required assessments.\n9. Written informed consent for study participation must be signed and dated by the patient and the investigator prior to any study-related intervention.\n\nExclusion Criteria:\n\n1. Inability to undergo brain or spine MRI.\n2. Concurrent treatment with other systemic tumor-directed pharmacotherapies.\n3. Intent to be treated with radiotherapy.\n4. Any investigational antitumor therapy other than those under investigation in this study.\n5. Judgment by the investigator that the patient should not participate in the study because the patient is unlikely to comply with study procedures, restrictions and requirements.\n6. Intention to become pregnant during the course of the study or pregnancy. Women of childbearing potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum pregnancy test.\n7. Women who are breast feeding and who do not agree to discontinue nursing prior to the first study treatment and for the period defined in the protocol.\n8. Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study.",{"count":331,"type":22},40,[26],"Advanced technology of ex vivo drug profiling referred to as pharmacoscopy may allow to identify novel drugs for the treatment of glioblastoma and other refractory brain tumors at an individual patient level. This personalized therapeutic approach was developed and validated in pre-clinical glioma models. With the current research proposal, we seek to establish feasibility for a clinical interventional trial for patients with refractory primary brain tumors that is based on pharmacoscopy-guided selection of treatment.\n\nThe study is supported by an unrestricted grant from Anti Cancer Fund.",[335,109,225,32,31,104,336,337],"Brain (Nervous System) Cancers","Rare Primary Brain Tumors","Rare CNS Primary Tumors",[339,340,341,342,343],"pharmacoscopy","drug testing","refractory tumor","drug repurposing","personalized medicine","2026-04-29",{"date":291,"type":48},{"date":347,"type":22},"2026-06-01",{"date":349,"type":22},"2028-09-15",{"name":351,"class":55},"University of Zurich",{"id":353,"slug":354,"hasResults":11,"nctId":355,"briefTitle":356,"officialTitle":357,"acronym":358,"eligibilityCriteria":359,"healthyVolunteers":11,"sex":17,"minAge":360,"maxAge":361,"enrollmentInfo":362,"targetDuration":4,"studyType":23,"phases":364,"briefSummary":366,"conditions":367,"keywords":370,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":374,"lastUpdatePostDateStruct":375,"startDateStruct":377,"completionDateStruct":379,"leadSponsor":381,"locationsCount":383},"100443691","individualized-treatment-plan-in-children-and-young-adults-with-relapsed-medulloblastoma-and-ependymoma-100443691","NCT05057702","Individualized Treatment Plan in Children and Young Adults With Relapsed Medulloblastoma and Ependymoma","A Pilot Feasibility and Efficacy (Phase 2) Trial of Real Time Drug Screening and Genomic Testing to Determine an Individualized Treatment Plan in Children and Young Adults With Relapsed Medulloblastoma and Ependymoma","PNOC027","Inclusion Criteria:\n\n1. Participants must have recurrent medulloblastoma or recurrent ependymoma previously histologically confirmed. Participants must be experiencing their first or second relapse to be eligible.\n2. Participants must have surgically accessible disease.\n3. Prior Therapy:\n\n   1. The participant must have received at least one prior therapy at the time of initial diagnosis.\n   2. Relapsed medulloblastoma or relapsed ependymoma are eligible.\n   3. Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study and would be eligible for surgical resection per institutional guidelines\n\n      * Participants must have received last chemotherapy or biologic agent at least 7 days prior to registration.\n      * Monoclonal antibody treatment: \\> 21 days prior to registration.\n      * Bevacizumab participants must have received last dose \\> 21 days prior to study registration\n4. Participant must be a candidate for surgical resection or biopsy with anticipated ability to obtain the minimum tissue requirements for study.\n5. Radiation - Participants must have:\n\n   1. Had their last fraction of local irradiation to primary tumor \\>= 12 weeks prior to registration.\n   2. Had their last fraction of craniospinal irradiation or total body irradiation \\>= 12 weeks prior to registration\n   3. At least 14 days after local palliative radiation (small-port)\n6. Age \\>=12 months to \\\u003C= 39 years of age.\n7. Karnofsky \\>= 50 for participants \\> 16 years of age and Lansky \\>= 50 for participants \\\u003C= 16 years of age. Participants 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.\n8. Corticosteroids: Participants who are receiving dexamethasone or equivalent must be on a stable or decreasing dose for at least 1 week prior to registration.\n9. Organ Function Requirements (within 7 days prior to study registration)\n\n   1. Adequate Bone Marrow Function Defined as:\n\n      * Peripheral absolute neutrophil count (ANC) \\>= 750\u002Fmm\\^3\n      * Platelet count \\>= 75,000\u002Fmm\\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n      * Hemoglobin \\>= 8 g\u002Fdl.\n   2. Adequate Renal Function Defined as:\n\n      * Creatinine clearance or radioisotope GFR \\>= 70 milliliter\u002Fminute (mL\u002Fmin) \u002F1.73 m\\^2 or\n      * A serum creatinine based on age\u002Fsex as follows:\n\n      Age \u002F Maximum Serum Creatinine (mg\u002FdL) Male \u002F Maximum Serum Creatinine (mg\u002FdL) Female.\n      * 1 to \\\u003C 2 years \u002F 0.6 \u002F 0.6.\n      * 2 to \\\u003C 6 years \u002F 0.8 \u002F 0.8.\n      * 6 to \\\u003C 10 years \u002F 1 \u002F 1.\n      * 10 to \\\u003C 13 years \u002F 1.2 \u002F 1.2.\n      * 13 to \\\u003C 16 years \u002F 1.5 \u002F 1.4.\n      * \\>= 16 years \u002F 1.7 \u002F 1.4.\n      * \\- The threshold creatinine values in this table were derived from the Schwartz formula for estimating Glomerular filtration rate (GFR) utilizing child length and stature data published by the Center for Disease Control (CDC) (Schwartz GJ and Gauthier B 1985).\n   3. Adequate Liver Function Defined as:\n\n      * Total Bilirubin \\\u003C= 1.5 x upper limit of normal (ULN) for age; in presence of Gilbert's syndrome, total bilirubin \\\u003C 3 x ULN or direct bilirubin \\\u003C 1.5 x ULN.\n      * Alanine aminotransferase (ALT) \\\u003C= 3x ULN.\n      * Aspartate aminotransferase (AST) \\\u003C= 3x ULN.\n10. The effects of the agents used in this study on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 4 months after completion of therapy administration. Should a woman become pregnant or suspect pregnancy while participating in this study, the treating physician should be informed immediately.\n11. Adequate neurologic function defined as participants with seizure disorder may be enrolled if seizures are well controlled. Participants on non-enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drug.\n12. Participants must enroll on the Protocol for Children and Young Adults Diagnosed with a Central Nervous System (CNS) Tumor to Assess Cognitive, Quality of Life (QOL), and Comprehensive Effects of Therapies (PNOC COMP) study if PNOC COMP is open to accrual at the enrolling institution\n13. A legal parent\u002Fguardian or participant must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.\n\nExclusion Criteria:\n\n1. Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.\n2. Participants who are receiving any other investigational agents.\n3. Participants must be at least 7 days since the completion of therapy with a biologic or small molecule agent. For any agent with known adverse events that can occur beyond 7 days after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur. Such participants should also be discussed with study chairs.\n4. Participants who are currently taking any anti-cancer direct therapy. Steroids are not considered anti-cancer therapy.\n5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection.\n6. Women of childbearing potential must not be pregnant or breast-feeding. A negative serum or urine pregnancy test is required prior to start of therapy.\n7. Participants must not receive any tumor-directed therapy after enrollment, except for surgical resection\u002F biopsy.\n\nImportant note: The eligibility criteria listed above are interpreted literally and cannot be waived.","12 Months","39 Years",{"count":363,"type":22},74,[365],"NA","The current study will use a new treatment approach based on the molecular characteristics of each participant's tumor. The study will test the feasibility in the pilot phase of performing real-time drug screening on tissue taken during surgery in patients with relapsed medulloblastoma or ependymoma and of having a specialized tumor board assign a treatment plan based on the results of this screening and genomic sequencing. The aim of this trial is to allow every child and young adult with relapsed medulloblastoma and ependymoma to receive the most effective and least toxic therapies currently available and will pave the way for improved understanding and treatment of these tumors in the future. Moreover, if successful, it could serve as a paradigm for personalized medicine programs for other types of cancer.",[31,71,117,32,368,369],"Ependymoma Malignant","Ependymoma of Brain",[371,372,373],"Individualized Treatment Plan","Genetic Screening","Screening","2026-04-13",{"date":376,"type":48},"2026-04-15",{"date":378,"type":48},"2022-02-22",{"date":380,"type":22},"2028-01-31",{"name":382,"class":55},"University of California, San Francisco",8,{"id":385,"slug":386,"hasResults":11,"nctId":387,"briefTitle":388,"officialTitle":389,"acronym":4,"eligibilityCriteria":390,"healthyVolunteers":11,"sex":17,"minAge":64,"maxAge":391,"enrollmentInfo":392,"targetDuration":4,"studyType":23,"phases":394,"briefSummary":395,"conditions":396,"keywords":403,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":405,"lastUpdatePostDateStruct":406,"startDateStruct":407,"completionDateStruct":409,"leadSponsor":411,"locationsCount":86},"100376708","phase-1-study-of-b7-h3-specific-car-t-cell-locoregional-immunotherapy-for-diffuse-intrinsic-pontine-gliomadiffuse-midline-glioma-and-recurrent-or-refractory-pediatric-central-nervous-system-tumors-100376708","NCT04185038","Study of B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma\u002FDiffuse Midline Glioma and Recurrent or Refractory Pediatric Central Nervous System Tumors","Phase 1 Study of B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma\u002FDiffuse Midline Glioma and Recurrent or Refractory Pediatric Central Nervous System Tumors","Inclusion Criteria:\n\n1. Age ≥ 1 and ≤ 26 years\n2. Diagnosis of refractory or recurrent CNS disease for which there is no standard therapy, or diagnosis of DIPG or DMG at any time point following completion of standard therapy\n3. Able to tolerate apheresis, or has apheresis product available for use in manufacturing\n4. CNS reservoir catheter, such as an Ommaya or Rickham catheter\n5. Life expectancy ≥ 8 weeks\n6. Lansky or Karnofsky score ≥ 60\n7. If patient does not have previously obtained apheresis product, patient must have discontinued, and recovered from acute toxic effects of, all prior chemotherapy, immunotherapy, and radiotherapy and discontinue the following prior to enrollment:\n\n   1. ≥ 7 days post last chemotherapy\u002Fbiologic therapy administration\n   2. 3 half lives or 30 days, whichever is shorter post last dose of anti-tumor antibody therapy\n   3. Must be at least 30 days from most recent cellular infusion\n   4. All systemically administered corticosteroid treatment therapy must be stable or decreasing within 1 week prior to enrollment with maximum dexamethasone dose of 2.5 mg\u002Fm2\u002Fday. Corticosteroid physiologic replacement therapy is allowed.\n8. Adequate organ function\n9. Adequate laboratory values\n10. Patients of childbearing\u002Ffathering potential must agree to use highly effective contraception\n\nExclusion Criteria:\n\n1. Presence of Grade ≥ 3 cardiac dysfunction or symptomatic arrhythmia requiring intervention\n2. Presence of primary immunodeficiency\u002Fbone marrow failure syndrome\n3. Presence of clinical and\u002For radiographic evidence of impending herniation\n4. Presence of \\>Grade 3 dysphagia\n5. Presence of active malignancy other than the primary CNS tumor under study\n6. Presence of active severe infection\n7. Receiving any anti-cancer agents or chemotherapy\n8. Pregnant or breastfeeding\n9. Subject and\u002For authorized legal representative unwilling or unable to provide consent\u002Fassent for participation in the 15 year follow up period\n10. Presence of any condition that, in the opinion of the investigator, would prohibit the patient from undergoing treatment under this protocol","26 Years",{"count":393,"type":22},90,[25],"This is a Phase 1 study of central nervous system (CNS) locoregional adoptive therapy with autologous CD4+ and CD8+ T cells lentivirally transduced to express a B7H3-specific chimeric antigen receptor (CAR) and EGFRt. CAR T cells are delivered via an indwelling catheter into the tumor resection cavity or ventricular system in children and young adults with diffuse intrinsic pontine glioma (DIPG), diffuse midline glioma (DMG), and recurrent or refractory CNS tumors.\n\nA child or young adult meeting all eligibility criteria, including having a CNS catheter placed into the tumor resection cavity or into their ventricular system, and meeting none of the exclusion criteria, will have their T cells collected. The T cells will then be bioengineered into a second-generation CAR T cell that targets B7H3-expressing tumor cells. Patients will be assigned to one of 3 treatment arms based on location or type of their tumor. Patients with supratentorial tumors will be assigned to Arm A, and will receive their treatment into the tumor cavity. Patients with either infratentorial or metastatic\u002Fleptomeningeal tumors will be assigned to Arm B, and will have their treatment delivered into the ventricular system. The first 3 patients enrolled onto the study must be at least 15 years of age and assigned to Arm A or Arm B. Patients with DIPG will be assigned to Arm C and have their treatment delivered into the ventricular system. The patient's newly engineered T cells will be administered via the indwelling catheter for two courses. In the first course patients in Arms A and B will receive a weekly dose of CAR T cells for three weeks, followed by a week off, an examination period, and then another course of weekly doses for three weeks. Patients in Arm C will receive a dose of CAR T cells every other week for 3 weeks, followed by a week off, an examination period, and then dosing every other week for 3 weeks. Following the two courses, patients in all Arms will undergo a series of studies including MRI to evaluate the effect of the CAR T cells and may have the opportunity to continue receiving additional courses of CAR T cells if the patient has not had adverse effects and if more of their T cells are available.\n\nThe hypothesis is that an adequate amount of B7H3-specific CAR T cells can be manufactured to complete two courses of treatment with 3 or 2 doses given on a weekly schedule followed by one week off in each course. The other hypothesis is that B7H3-specific CAR T cells can safely be administered through an indwelling CNS catheter or delivered directly into the brain via indwelling catheter to allow the T cells to directly interact with the tumor cells for each patient enrolled on the study. Secondary aims of the study will include evaluating CAR T cell distribution with the cerebrospinal fluid (CSF), the extent to which CAR T cells egress or traffic into the peripheral circulation or blood stream, and, if tissues samples from multiple timepoints are available, also evaluate disease response to B7-H3 CAR T cell locoregional therapy.",[397,398,29,32,71,399,312,400,401,402,225],"Central Nervous System Tumor","Diffuse Intrinsic Pontine Glioma","Germ Cell Tumor","Primitive Neuroectodermal Tumor","Choroid Plexus Carcinoma","Pineoblastoma, Childhood",[404],"CNS, CAR T cell, B7-H3, pediatric, young adult, brain tumor, DIPG, DMG","2026-04-07",{"date":374,"type":48},{"date":408,"type":48},"2019-12-11",{"date":410,"type":22},"2042-05",{"name":412,"class":55},"Seattle Children's Hospital",{"id":414,"slug":415,"hasResults":11,"nctId":416,"briefTitle":417,"officialTitle":418,"acronym":4,"eligibilityCriteria":419,"healthyVolunteers":11,"sex":17,"minAge":420,"maxAge":306,"enrollmentInfo":421,"targetDuration":4,"studyType":23,"phases":423,"briefSummary":424,"conditions":425,"keywords":432,"overallStatus":257,"whyStopped":4,"lastUpdateSubmitDate":436,"lastUpdatePostDateStruct":437,"startDateStruct":439,"completionDateStruct":441,"leadSponsor":443,"locationsCount":187},"100622970","phase-1-b7-h3cd28zcart-in-cns-neoplasms-100622970","NCT07390539","B7-H3.CD28Z.CART in CNS Neoplasms","A Phase 1\u002F1b Study of Autologous b7-h3 Chimeric Antigen Receptor t Cells (b7-h3.cd28z.Cart) in Children and Young Adults With Recurrent or Progressive Cns Neoplasms Expressing b7-h3 Target","Pre-screening Inclusion Criteria:\n\n* Participants must have histologically and\u002For molecularly confirmed CNS embryonal tumor (see eligible tumor types below), OR ependymoma that is recurrent\u002Fprogressive following standard of care treatment.\n\n  --Eligible CNS embryonal tumor types include:\n  * Medulloblastoma\n  * Atypical Teratoid Rhabdoid Tumor (ATRT)\n  * Embryonal Tumor with Multilayered Rosettes (ETMR) Pineoblastoma\n  * Other CNS embryonal tumor types, at the discretion of the study chair (or designee)\n* Participants must have adequate pre-trial tumor material available to determine B7- H3 expression status. Tumor tissue from the most recent resection or biopsy of recurrent disease is preferred. If unavailable, tumor tissue from prior recurrences or from time of initial diagnosis is acceptable. Biopsies will not be performed for participation in this research trial or for research purposes.\n* Pre-screening IHC Consent: All participants ≥ 18 years of age must be able to give informed consent. For participants \\\u003C18 years of age, their legal authorized representative (LAR) (i.e. parent or guardian) must give informed consent. Pediatric participants will be included in age-appropriate discussion and written assent will be obtained for those ≥10 years of age, where appropriate. If a minor becomes of age during participation of this study, they will be asked to reconsent as an adult.\n\nInclusion Criteria:\n\n* Participants must have histologically and\u002For molecularly confirmed CNS embryonal tumor (see eligible tumor types below), OR ependymoma that is recurrent\u002Fprogressive following standard of care treatment.\n\n  --Eligible CNS embryonal tumor types include:\n  * Medulloblastoma\n  * Atypical Teratoid Rhabdoid Tumor (ATRT)\n  * Embryonal Tumor with Multilayered Rosettes (ETMR)\n  * Pineoblastoma\n  * Other CNS embryonal tumor types, at the discretion of the study chair (or designee)\n* B7-H3 expression: Demonstration of B7-H3 expression with H score greater than 100 by immunohistochemistry (IHC) is required.\n* Age: greater than or equal to two (2) years of age and less than or equal to 21 years of age. The first participant treated at each dose level within each stratum (Standard Risk and High Risk) will be ≥ 6 years of age when feasible.\n* Disease status: Participants must have evaluable disease in the central nervous system to be eligible. Evaluable disease includes either measurable OR non-measurable disease, defined as follows:\n\n  --Measurable disease (contrast-enhancing or non-enhancing tumor)\n  * Clearly defined lesional margins with two perpendicular diameters of at least 10mm, OR\n  * At least two times (in both perpendicular diameters) the MRI slice thickness, plus the interslice gap\n\n    --Non-measurable disease (tumor that is too small to be accurately measured)\n  * Lesion that is measurable in only one perpendicular dimension, OR\n  * Lesion that is less than 10mm in at least one perpendicular dimension, OR\n  * Lesion that is less than two times the MRI slice thickness, plus the interslice gap\n  * Note: Leptomeningeal (LM) disease is considered non-measurable but evaluable.\n* Performance status: Karnofsky performance status ≥60% for participants ≥16 years of age and Lansky performance status ≥60% for participants \\\u003C16 years of age (see APPENDIX A PERFORMANCE STATUS CRITERIA). NOTE: Participants with neurologic deficits must have a stable neurologic exam for seven (7) days prior to enrollment. Participants 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.\n* Life expectancy of greater than 12 weeks\n* Prior therapy: Participants must have received prior standard of care therapy, including maximal safe surgical resection, radiation therapy and\u002For standard chemotherapy, and is recovered from all acute treatment-related toxicities (defined as ≤ Grade 1 or stable) from all prior therapy before entering this study There is no upper limit to the number of prior therapies allowed, but must have received all standard curative options for their tumor type.\n* Participants must meet the following washouts prior to enrollment:\n\n  * Radiation therapy - Participants must have had their last fraction of:\n\n    ---Craniospinal irradiation, whole brain radiation therapy, or radiation therapy to \\>50% of the pelvis or spine \\>28 days prior to enrollment\n\n    ---Focal irradiation (small port) \\>14 days prior to enrollment\n  * At least 14 days since any prior cytotoxic chemotherapy\n  * At least 7 days since any biologic antineoplastics, tyrosine kinase inhibitor, targeted agent\n  * At least 21 days or 5 half-lives (whichever is shorter) since any investigational antineoplastic or disease-directed agent (but at least 28 days from prior investigational antineoplastic vaccine therapy)\n  * At least 21 days since any monoclonal antibody therapy\n  * At least 90 days since any systemic inhibitor\u002Fstimulatory immune checkpoint therapy\n  * At least 28 days from prior autologous stem cell transplantation, with no ongoing toxicities\n  * At least 14 days after peg-filgrastim and 7 days for hematopoietic growth factor support\n* Steroid use: Must not require concurrent systemic steroid therapy, although physiologic corticosteroid replacement therapy for management of pituitary\u002Fadrenal insufficiency and\u002For topical administration (e.g. inhaled or dermatologic) is allowed. Use of topical, ocular, intranasal, or inhaled corticosteroids are permitted per PI\n\ndiscretion.\n\n* Participants must have adequate organ function, as defined below\n\n  --Adequate bone marrow function\n  * Hemoglobin ≥ 8 g\u002FdL\n  * Absolute neutrophil count (ANC) ≥ 1000 cells\u002FuL\n  * Absolute lymphocyte count (ALC) ≥ 150 cells\u002FuL\n  * Platelets ≥100,000\u002FuL (unsupported, defined as no platelet transfusion within 4 days)\n* Adequate renal function defined as creatinine within normal limits for age OR creatinine clearance (as estimated by Cockcroft Gault Equation for participants ≥ 18yo and Bedside Schwartz for participants \\\u003C18yo) ≥70mL\u002Fmin\n\n  * Maximum Serum Creatinine mg\u002FDL ---6 months to 1 year Male 0.5 Female 0.5 ---1 to \\\u003C 2 years Male 0.6 Female 0.6 ---2 to \\\u003C 6 years Male 0.8 Female 0.8\n\n    * 6 to \\\u003C 10 years Male 1 Female 1\n    * 10 to \\\u003C 13 years Male 1.2 Female 1.2\n    * 13 years to \\\u003C 16 years Male 1.5 Female 1.4\n\n      * 16 years Male 1.7 Female 1.4\n* Adequate hepatic function\n\n  * Serum ALT\u002FAST ≤3.0 upper limit of normal (ULN)\n  * Total bilirubin ≤1.5mg\u002FdL, except in subjects with confirmed Gilbert's syndrome\n* Adequate cardiac function\n\n  --Ejection fraction ≥50% or fractional shortening ≥28%, measured by echocardiography\n* Adequate pulmonary function\n\n  * No evidence of dyspnea at rest\n  * Pulse oximetry \\>92% whilst breathing room air\n* Adequate neurologic function\n\n  * Participants with seizure disorders on anticonvulsants may be enrolled if seizures are well controlled (no seizure activity within 7 days prior to enrollment)\n  * Nervous system disorders (CTCAE v6.0) resulting from prior therapy must be ≤ Grade 2, with the exception of decreased tendon reflex (DTR; any Grade eligible). Participants with neurological deficits should be stable for a minimum of 7 days prior to enrollment. (A baseline detailed neurological exam should clearly document the neurological status of the participant prior at enrollment).\n* Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization are not considered to be of childbearing potential)\n* Participants of childbearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for one year after receiving the preparative lymphodepletion regimen, or for as long as B7- H3.CD28Z.CART cells are detectable in peripheral blood or CSF, whichever is later.\n* Participant or parent of participant or legally recognized representative must be able to sign a written informed consent document. Pediatric participants will be included in age-appropriate discussion and written assent will be obtained for those ≥10 years of age, where appropriate.\n\nExclusion Criteria:\n\n* Participants with bulky tumor are ineligible. Bulky tumor is defined as:\n\n  * Tumor with diameter of \\>5cm in one dimension on T2\u002FFLAIR sequence\n  * Tumor with evidence of clinically significant midline shift or uncal herniation\n  * Tumor that, in opinion of the site investigator, shows significant mass effect in either the brain or spine\n* Participants with clinical or radiological evidence of brain herniation.\n* Participants who have received other B7-H3 targeted cellular therapies. Other prior cellular therapies are eligible, including immune checkpoint inhibition and vaccine therapy. These prior therapies should be discussed with the study chair (or designee) prior to participant enrollment.\n* Concurrent illness\n\n  * Participants with any prior immunodeficiency or history of autoimmune disease requiring systemic steroids\u002F immunosuppressive medication\u002F disease-modifying agents within the last two (2) years.\n  * Uncontrolled (Grade 3) bacterial, viral, fungal, or other infection.\n  * Ongoing infection with HIV or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive). A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and\u002For nucleic acid testing.\n  * Evidence of severe or uncontrolled systemic disease (e.g. Grade 3 significant cardiac, pulmonary, hepatic, renal or other organ dysfunction) that in the judgement of the principal investigator is likely to interfere with assessment of safety or efficacy of the investigational regimen and its requirements.\n  * Known sensitivity or allergy to any of the agents\u002Freagents used in this study (i.e. DSMO, cyclophosphamide, fludarabine)\n  * History of severe hypersensitivity reaction to compounds of similar chemical or biologic compositions to any agent used in the study or in the manufacturing of cells.\n* Concomitant medications\n\n  * Current systemic corticosteroid therapy\n  * Note, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency will be allowed.\n  * Participants who are receiving any other anti-cancer or investigational drug therapy are ineligible.\n  * Participants who have received the last vaccination of a live vaccine ≤ 30 days prior to the start of treatment are ineligible.\n  * Ongoing use of dietary supplements, alternative therapies or extreme diets, or any medication not approved by the study chair (or designee).\n* Any other condition which in the principal investigator's opinion makes the individual clinically unsuitable to participate in this trial, or which would jeopardize compliance with the protocol, or would make it difficult to interpret adverse events or study data.","2 Years",{"count":422,"type":22},70,[25],"The purpose of this research study is to test the safety and effectiveness of a cell therapy at different doses for children and young adults with recurrent or progressive brain tumors. Recurrent\u002Frecurred means a tumor that has gone away and then came back. This cell therapy is called B7- H3.CD28Z.CART, referred to as B7-H3 CAR T cells. B7-H3 is a protein that is over-expressed on many tumor cells, making it a good target for cancer cell therapy.\n\nThe names of the study investigational therapies involved in this study are:\n\n* Fludarabine (a type of chemotherapy)\n* Cyclophosphamide (a type of chemotherapy)\n* B7-H3 CAR T cells (a type of cellular therapy)",[311,426,427,428,429,31,71,430,117,32,312,73,74,431],"Brain Tumor","Brain Tumor, Recurrent","Brain Tumor, Pediatric","Brain Tumor Adult","Medulloblastoma, Adult","Leptomeningeal Disease",[311,426,428,433,434,31,71,430,117,32,312,435,74,431],"Brain Tumor, Adult","Brain Tumor Recurrent","Embryonal Tumor with Multilayered Rosettes","2026-01-28",{"date":438,"type":48},"2026-02-05",{"date":440,"type":22},"2026-07",{"date":442,"type":22},"2032-08-31",{"name":444,"class":55},"Robbie Majzner",{"id":446,"slug":447,"hasResults":11,"nctId":448,"briefTitle":449,"officialTitle":450,"acronym":4,"eligibilityCriteria":451,"healthyVolunteers":11,"sex":17,"minAge":95,"maxAge":19,"enrollmentInfo":452,"targetDuration":4,"studyType":23,"phases":454,"briefSummary":455,"conditions":456,"keywords":458,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":479,"lastUpdatePostDateStruct":480,"startDateStruct":482,"completionDateStruct":484,"leadSponsor":486,"locationsCount":86},"100447427","phase-1-chemo-immunotherapy-using-ibrutinib-plus-indoximod-for-patients-with-pediatric-brain-cancer-100447427","NCT05106296","Chemo-immunotherapy Using Ibrutinib Plus Indoximod for Patients With Pediatric Brain Cancer","Repurposing Ibrutinib for Chemo-Immunotherapy in a Phase 1b Study of Ibrutinib With Indoximod Plus Metronomic Cyclophosphamide and Etoposide for Pediatric Patients With Brain Cancer","Inclusion Criteria:\n\nDiagnosis:\n\n* Patients must have prior documented progressive or refractory disease with histologically proven initial diagnosis of ependymoma, medulloblastoma, glioblastoma, or another type of primary cancer of the central nervous system with no curative conventional therapy options available.\n* Metastatic disease is acceptable.\n* Patients must have MRI confirmation (with and without gadolinium contrast) of current active disease.\n\nPatients must be able to swallow pills.\n\nLansky or Karnofsky performance status score must be ≥ 50%.\n\nAdequate renal function:\n\n* Creatinine clearance (CLcr) \\> 25 mL\u002Fmin (by calculated methods) AND Creatinine ≤ 1.5-times upper limit of age-adjusted normal for age of patient.\n\nAdequate liver function:\n\n* Alanine aminotransferase (ALT) ≤ 3-times upper limit of normal.\n* Aspartate aminotransferase (AST) ≤ 3-times upper limit of normal.\n* Total bilirubin ≤ 1.5-times upper limit of normal unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin.\n\nAdequate bone marrow function:\n\n* Absolute neutrophil count (ANC) ≥ 1000\u002Fmm3 (independent of growth factor support).\n* Platelets ≥ 100,000\u002Fmm3 (independent of transfusion support).\n* Hemoglobin ≥ 8 g\u002FdL (independent of transfusion support).\n\nSeizure disorders must be well controlled on antiepileptic medication.\n\nPrior therapy:\n\n* Patients previously treated with chemotherapy drugs included in this protocol are eligible for enrollment.\n* At the time of Screening, patients must be at least 21 days from the administration of any investigational agent (other than indoximod) or prior cytotoxic therapy (including chemotherapy).\n* At the time of Screening, patients must be at least 28 days from administration of antibody-based therapies (e.g., bevacizumab), tumor-directed vaccines, or cellular immune therapies (e.g., T cells, NK cells, etc.).\n* At the time of Screening, patients must be at least 56 days from administration of tumor-directed therapies using infectious agents (e.g., viruses, bacteria, etc.).\n* At the time of Screening, patients must be at least 90 days from any radiation or proton therapy (all modalities, including radiosurgery) that targeted all sites of known disease.\n* There is no lock-out window for patients who were treated with focal radiation or focal proton therapy (all modalities, including radiosurgery) that did not target all disease sites, if at least one site of active tumor is expected to persist and\u002For grow.\n\nConcurrent anti-neoplastic therapy:\n\n* No investigational or commercial agents, including intrathecal drugs, other than that described by this clinical study protocol (GCC2020) may be administered with the intent to treat the patient's malignancy while they remain enrolled on this study.\n\nContraception, pregnancy, and breastfeeding:\n\n* Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study. Men must agree to not donate sperm during and for 3 months after the study.\n* Women who are pregnant or breastfeeding are ineligible for this study.\n* Patients who become pregnant while participating in this study will have to stop Study Therapy.\n\nPatients, or their parent for patients less than 18 years of age, must sign an Informed Consent Document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study.\n\n.\n\nExclusion Criteria:\n\nPatients who are unable to swallow pills.\n\nPatients with known hypersensitivity to any drugs in the treatment plan.\n\nPatients with active autoimmune disease that requires systemic therapy.\n\n* Allergies, allergic conditions, and reactive inflammatory conditions that are not autoimmune in nature would not exclude patients (e.g., eczema, asthma, etc.).\n\nPregnant or breastfeeding women.\n\nMajor surgery or a wound that has not fully healed within 4 weeks of Screening.\n\nKnown central nervous system lymphoma.\n\nPatients with active bleeding or history of thrombotic or hemorrhagic stroke, or intracranial hemorrhage, within 6 months prior to Screening; with the exception of retained blood products from recent prior uncomplicated surgery (e.g., tumor biopsy, debulking, or resection; VP shunt placement, etc.).\n\nRequires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon).\n\nRequires chronic treatment with strong CYP3A inhibitor drugs.\n\nClinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification.\n\nPatients with baseline QTc interval of more than 470 msec at the time of Screening, and patients with congenital long QT syndrome.\n\nVaccinated with live, attenuated vaccines within 4 weeks of Screening.\n\nKnown history of human immunodeficiency virus (HIV) or active Hepatitis C Virus or active Hepatitis B Virus infection or any uncontrolled active systemic infection.\n\nAny life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of ibrutinib, indoximod, or chemotherapy, or put the study outcomes at undue risk.",{"count":453,"type":22},37,[25],"Recent lab-based discoveries suggest that IDO (indoleamine 2,3-dioxygenase) and BTK (Bruton's tyrosine Kinase) form a closely linked metabolic checkpoint in tumor-associated antigen-presenting cells. The central clinical hypothesis for the GCC2020 study is that combining ibrutinib (BTK-inhibitor) with indoximod (IDO-inhibitor) during chemotherapy will synergistically enhance anti-tumor immune responses, leading to improvement in clinical response with manageable overlapping toxicity.\n\nThe GCC2020 trial is a prospective open-label phase 1 trial to determine the best safe dose of the BTK-inhibitor ibrutinib to use in combination with previously studied chemo-immunotherapy regimens comprised of the investigational IDO-inhibitor indoximod plus oral palliative chemotherapy for participants, age 6 to 25 years, with relapsed or refractory primary brain cancer. Those previously treated with indoximod-based therapy may be eligible, including prior treatment via the phase 2 indoximod study (GCC1949, NCT04049669), the now closed phase 1 study (NLG2105, NCT02502708), or any expanded access (compassionate use) protocols. Ibrutinib will be combined with either indoximod plus oral cyclophosphamide and etoposide (Regimen A) or indoximod plus oral temozolomide (Regimen B). No cross-over between these two regimens will be allowed. Dose-escalation cohorts will determine the best safe dose of ibrutinib for each of these regimens. This will be followed by expansion cohorts, using ibrutinib at the best safe dose for each regimen, to allow assessment of preliminary evidence of efficacy.",[32,31,109,457],"Primary Brain Tumor",[459,460,461,462,463,464,465,466,467,468,469,470,471,288,472,473,474,475,476,477,478],"IDO","indoleamine 2,3-dioxygenase","indoximod","BTK","Bruton's Tyrosine Kinase","ibrutinib","immunotherapy","pediatric","childhood","brain tumor","brain cancer","glioblastoma","medulloblastoma","PNET","cyclophosphamide","etoposide","immune","central nervous system","CNS","temozolomide","2026-01-07",{"date":481,"type":48},"2026-01-09",{"date":483,"type":48},"2022-02-08",{"date":485,"type":22},"2028-09-30",{"name":487,"class":55},"Theodore S. Johnson",{"id":489,"slug":490,"hasResults":11,"nctId":491,"briefTitle":492,"officialTitle":493,"acronym":4,"eligibilityCriteria":494,"healthyVolunteers":11,"sex":17,"minAge":218,"maxAge":4,"enrollmentInfo":495,"targetDuration":4,"studyType":23,"phases":497,"briefSummary":498,"conditions":499,"keywords":518,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":519,"lastUpdatePostDateStruct":520,"startDateStruct":522,"completionDateStruct":524,"leadSponsor":526,"locationsCount":86},"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.",{"count":496,"type":22},102,[25],"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.",[311,109,500,501,502,503,504,505,506,507,313,32,508,31,509,510,511,512,513,514,515,516,517],"Gliosarcoma, Adult","Anaplastic Oligodendroglioma","Anaplastic Astrocytoma","Pilocytic Astrocytoma","Oligodendroglioma","Gliomatosis Cerebri","Pleomorphic Xanthoastrocytoma","Anaplastic Pleomorphic Xanthoastrocytoma","Ependymoma, Anaplastic","Teratoid Rhabdoid Tumor","Neuroectodermal Tumors, Primitive","Neuroectodermal Tumors","Anaplastic Meningioma","Atypical Meningioma","Choroid Plexus Neoplasms","Pineal Tumor","Diffuse Astrocytoma","Glial Tumor",[109,502,501,516,504],"2025-12-17",{"date":521,"type":48},"2025-12-18",{"date":523,"type":48},"2020-10-26",{"date":525,"type":22},"2026-12",{"name":527,"class":528},"Jazz Pharmaceuticals","INDUSTRY",{"id":530,"slug":531,"hasResults":11,"nctId":532,"briefTitle":533,"officialTitle":534,"acronym":4,"eligibilityCriteria":535,"healthyVolunteers":11,"sex":17,"minAge":218,"maxAge":4,"enrollmentInfo":536,"targetDuration":538,"studyType":251,"phases":4,"briefSummary":539,"conditions":540,"keywords":549,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":557,"lastUpdatePostDateStruct":558,"startDateStruct":559,"completionDateStruct":561,"leadSponsor":563,"locationsCount":566},"100459206","observational-study-for-assessing-treatment-and-outcome-of-patients-with-primary-brain-tumours-using-cimpact-now-and-2021-who-classification-100459206","NCT05259605","Observational Study for Assessing Treatment and Outcome of Patients With Primary Brain Tumours Using cIMPACT-NOW and 2021 WHO Classification","Observational Study for Assessing Treatment and Outcome of Patients With Primary Brain Tumours Diagnosed According to cIMPACT-NOW Recommendations and the 2021 WHO Classification","* Age ≥ legal age of consent\n* Newly diagnosed or recurrent primary brain tumours within one of the 17 cohorts of interest\n* Archival tumour tissue from primary tumour available at the site. Representative tissue from first surgery is preferred, but tissue from surgery for recurrence is allowed. Exception: only tissue from first surgery is allowed for Cohort 16.\n* Available MRI\u002FCT scans from primary brain tumour at initial diagnosis\n* Patient's consent\n\nDeceased patient:\n\nThe clinical data and\u002For biological material and\u002For CT\u002FMRI\u002FPET images can be accessed and used if at least one of the following three conditions is met:\n\n* The patient agreed beforehand in his\u002Fher lifetime to a further use of his\u002Fher data and\u002For biological material and\u002For CT\u002FMRI\u002FPET images, or,\n* There is consent of a relative to use data and\u002For biological material and\u002For CT\u002FMRI\u002FPET images of the deceased patient, or,\n* There is a reference to a corresponding legal declaration covering the exemption in case of the impossibility or disproportion of getting access to an informed consent (e.g., causing strain on relatives of deceased patients).\n\nAdditionally, in all cases the following three points need to be fulfilled:\n\n* No documentation of previous objection of the patient to the (re-)use of their data, biological material, CT\u002FMR\u002FPET images for research purposes\n* A notification to an ethics committee for the re-use of these data, biological material and CT\u002FMRI\u002FPET images\n* Any other national requirements are fulfilled, if applicable",{"count":537,"type":22},1650,"10 Years","Every new classification depends on its prognostic power and on the type of treatment given. With the rapid evolution of diagnostic methods and the advance in new treatments, there is much less reliable information available on how patients with newly defined brain tumour entities should be treated and what to expect from the current treatments.\n\nThe goal is to determine whether the new 2021 WHO classification, based on cIMPACT-NOW recommendations, results in more homogeneous patient groups than the old 2016 classification. Furthermore, it will help derive provisional guidelines on how patients with these newly defined tumour entities are best treated. These recommendations will be based on the experience of EORTC investigators with chosen treatments and their experience as reported in this data collection report.",[225,541,542,543,399,544,313,32,545,515,546,547,548],"Glioneuronal Tumor","Choroid Plexus Tumor","Pineal Tumors","Tumor of the Sellar Region","Embryonal Tumor","Hemangiopericytoma","Hemangioblastoma","Melanocytic Tumor of CNS",[550,551,552,553,554,555,556],"Rare primary brain tumor","2021 WHO Classification","molecular diagnosis","Gliomas","Choroid plexus tumors","Embryonal tumors","Pineal tumors","2025-12-11",{"date":519,"type":48},{"date":560,"type":48},"2023-03-21",{"date":562,"type":22},"2038-07-29",{"name":564,"class":565},"European Organisation for Research and Treatment of Cancer - EORTC","NETWORK",42,{"id":568,"slug":569,"hasResults":11,"nctId":570,"briefTitle":571,"officialTitle":572,"acronym":4,"eligibilityCriteria":573,"healthyVolunteers":11,"sex":17,"minAge":574,"maxAge":306,"enrollmentInfo":575,"targetDuration":4,"studyType":23,"phases":577,"briefSummary":578,"conditions":579,"keywords":4,"overallStatus":257,"whyStopped":4,"lastUpdateSubmitDate":580,"lastUpdatePostDateStruct":581,"startDateStruct":583,"completionDateStruct":585,"leadSponsor":587,"locationsCount":4},"100597679","phase-1-determine-maximum-tolerated-dose-safety-and-tolerability-of-rhenium-186re-in-pediatric-recurrent-refractory-or-progressive-ependymoma-and-high-grade-glioma-100597679","NCT07061626","Determine Maximum Tolerated Dose, Safety, and Tolerability of Rhenium (186Re) in Pediatric Recurrent, Refractory or Progressive Ependymoma and High-Grade Glioma","A Two-Part, Phase 1\u002F2a Trial to Determine the Maximum Tolerated Dose, Safety, and Tolerability of Rhenium (186Re) Obisbemeda (Rhenium-186 NanoLiposome, 186RNL) Delivered Via Convection Enhanced Delivery (CED) in Supratentorial Recurrent, Refractory, or Progressive Pediatric Ependymoma and High-Grade Glioma (HGG)","Inclusion Criteria:\n\n1. 6 years to 21 years\\* of age.\n2. Lesion number and size:\n\n   1. Phase 1a\u002Fb only: A single lesion (less than or equal to) ≤3.5 cm (longest axis) and volume of (less than or equal to) ≤22.4 mL as the largest tumor (subsequent to individual Cohort lesion size requirements).\n   2. Phase 2a only: A single lesion or any number of multiple lesions separated by (less than or equal to) ≤3 cm; each lesion (less than or equal to) ≤3.5 cm (longest axis) and volume of (less than or equal to) ≤22.4 mL as the largest tumor.\n3. Diagnosis:\n\n   a) Documented recurrent, refractory, or progressive ependymoma or HGG not eligible for resection or no longer receiving standard of care.\n\n   i) Phase 2a only: May include patients with recurrent, refractory, or progressive ependymoma or HGG where SOC surgery could be safely delayed four (4) weeks post-infusate.\n\n   b) Documented histologically confirmed high-grade glioma \\[following 2021 WHO CNS5 glioma nomenclature, e.g., Anaplastic astrocytoma, Anaplastic pleomorphic xanthoastrocytoma (PXA), Anaplastic ganglioglioma, Anaplastic oligodendroglioma, Glioblastoma, Diffuse midline glioma, H3K27M mutant\\].\n4. Karnofsky Performance Status ≥ 60. For subjects \\\u003C16 years of age, Lansky score ≥ 60.\n5. Acceptable liver function:\n\n   1. Bilirubin ≤ 1.5 times the upper limit of normal\n   2. AST (SGOT) and ALT (SGPT) ≤ 3.0 times the upper limit of normal (ULN)\n\n      6\\) Acceptable renal function:\n\n   \u003C!-- -->\n\n   1. Serum creatinine ≤1.5xULN\n\n7\\. Acceptable hematologic status (without hematologic support):\n\n1. ANC ≥1000 cells\u002FuL\n2. Platelet count ≥100,000\u002FuL\n3. Hemoglobin ≥9.0 g\u002FdL\n\n   8\\. All subjects of childbearing potential must have a negative serum pregnancy test, and subjects must agree to use effective means of contraception (for example, surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose.\n\n   9\\. Life expectancy of at least 2 months.\n\n   \\*Will consider treatment of subjects up to 25 years of age on a per-patient basis if no other co-morbidities are present that require subspecialty consultation outside of neurosurgical and oncologic care.\n\nExclusion Criteria:\n\n1. Spinal disease.\n2. Infratentorial location of tumor.\n3. Involvement of the leptomeninges.\n4. Serious intercurrent illness, as determined by the treating physician, which would compromise either patient safety or study outcomes such as:\n\n   1. Hypertension (two or more blood pressure readings performed at screening of systolic blood pressure (SBP) or diastolic blood pressure (DBP) above 95th percentile for age) despite optimal treatment.\n   2. Active medically significant infection unresponsive to antibiotics (e.g., non-healing wound, ulcer), uncontrolled systemic infection, or bone fracture.\n   3. Clinically significant cardiac arrhythmias.\n   4. Untreated hypothyroidism.\n   5. Congestive heart failure.\n   6. Myocarditis.\n   7. Inherited bleeding diathesis or coagulopathy with the risk of bleeding.\n   8. Known active malignancy other than ependymoma or high-grade glioma.\n5. Any of the following prior anticancer therapy:\n\n   1. Prior treatment with Bevacizumab or other VEGF agents within 12 months prior to study registration.\n   2. Non-standard radiation therapy such as brachytherapy, systemic radioisotope therapy, or intra-operative radiotherapy (IORT) to the target site at any time prior to study registration.\n   3. Standard radiation therapy within 12 weeks prior to study registration.\n   4. Any systemic therapy within 28 days or 2 half-lives, whichever is longer, prior to study registration (this may include investigational agents, small-molecule kinase inhibitors, non-cytotoxic hormonal therapy, biologic agents, metronomic\u002Fprotracted low-dose chemotherapy, etc.).\n   5. Nitrosoureas or mitomycin C within 42 days prior to study registration.\n6. Psychiatric illness\u002Fsocial situations that would limit compliance with the study requirements.\n7. A tumor located within 1.0cm of a ventricle AND it is determined by the surgeon, PI, and Sponsor to be a risk for drug extravasation to the subarachnoid space if given catheter placement and drug administration.\n8. A tumor within 1.5cm of critical structures, including the optic chiasm, optic nerves, or brainstem.\n9. Evidence of acute intracranial or intratumoral hemorrhage either by magnetic resonance imaging (MRI) or computerized tomography (CT) scan (subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin are eligible).\n10. Treatment with antiepileptic medications must have a two-week history of a stable dose of antiepileptic without seizures prior to study registration.\n11. Patients with corticosteroid requirements to control cerebral edema must be maintained at a stable or decreasing dose for a minimum of two weeks without progression of clinical symptoms prior to study registration.","6 Years",{"count":576,"type":22},56,[25],"Pediatric patients 6-21 years of age with supratentorial recurrent, refractory, or progressive pediatric ependymoma and high-grade glioma (HGG) will be included in this study of treatment with Rhenium-186 Nanoliposome (186RNL). Phase 1 of the study will look to determine the maximum tolerated dose (MTD) of 186RNL in this patient population. Phase 2 of the study will use the recommended dose determined in Phase 1 to continue to look at overall response rate and progression-free survival following 186RNL treatment.",[32,103],"2025-07-10",{"date":582,"type":48},"2025-07-11",{"date":584,"type":22},"2025-09",{"date":586,"type":22},"2027-03",{"name":588,"class":528},"Plus Therapeutics",{"id":590,"slug":591,"hasResults":11,"nctId":592,"briefTitle":593,"officialTitle":594,"acronym":595,"eligibilityCriteria":596,"healthyVolunteers":11,"sex":17,"minAge":597,"maxAge":361,"enrollmentInfo":598,"targetDuration":4,"studyType":251,"phases":4,"briefSummary":600,"conditions":601,"keywords":602,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":607,"lastUpdatePostDateStruct":608,"startDateStruct":610,"completionDateStruct":612,"leadSponsor":614,"locationsCount":86},"100575992","systemic-biomarkers-to-predict-radiation-induced-neurocognitive-decline-100575992","NCT06779487","Systemic Biomarkers to Predict Radiation-Induced Neurocognitive Decline","Systemic Biomarkers to Predict Radiation-Induced Neurocognitive Decline in Pediatric and Young Adults With Primary Brain Tumors (BIO-RIN)","BIO-RIN","Inclusion Criteria:\n\n1. Age 5-39 years\n2. Histological diagnosis of primary brain tumor\n3. Decision for treatment with radical intent radiotherapy\n4. Signed assent and parental consent form for pediatric age group and signed consent form for adults.\n\nExclusion Criteria:\n\n1. Inability to undergo neurocognitive evaluation\n2. Palliative radiotherapy.\n3. Expected life expectancy \\\u003C 1 year","5 Years",{"count":599,"type":22},200,"Radiation constitutes an integral component in the management of primary brain tumors in pediatric and young adults like medulloblastoma, ependymoma, low-grade glioma, pituitary tumors, etc. A decline in neurocognitive outcomes is a multifactorial effect occurring from the primary disease as well as associated with treatments, including radiation. Since many of these tumors are highly curable, it is crucial to reduce long-term side effects, including memory loss, to improve the quality of life in these patients, leading to better rehabilitation. Radiation-induced neurocognitive deterioration is postulated to occur from multiple factors like neuroinflammation, vascular damage, and depletion of neural stem cells. The proposed study will prospectively evaluate 200 pediatric and young adults with brain tumors treated with radiotherapy. Biological samples (peripheral blood and cerebrospinal fluid) will be procured during routine investigations (an additional amount will be collected for study purposes without the need for additional investigations). Serial blood markers (whenever available pre-operative and before, during, and after completion of radiation) of neuroinflammation and neural markers will be tested in patients undergoing radiation as part of their standard treatment, and correlate with the neurocognitive outcomes measured by age-appropriate Wechsler intelligence scales. Also, the impact of clinical (e.g. age) and radiotherapy parameters like volume, dose of radiation, and technique (photon versus proton therapy) on acute (during radiotherapy) and late systemic inflammatory markers will be analyzed. The study will even provide the opportunity to know the influence of radiation on systemic neuroinflammatory markers in the human population, providing better biological insights into the neurocognitive decline. If proven successful, these biomarkers can be used in routine clinical practice for early intervention to improve neurocognitive function in patients receiving radiation (even for other histology or other patients receiving radiation like brain metastasis).",[227,31,225,32],[426,603,604,605,606],"Radiotherapy","Proton Beam Therapy","Neuro-cognition","Bio-markers","2025-04-08",{"date":609,"type":48},"2025-04-11",{"date":611,"type":48},"2025-02-11",{"date":613,"type":22},"2032-02",{"name":615,"class":55},"Tata Memorial Centre",{"id":617,"slug":618,"hasResults":11,"nctId":619,"briefTitle":620,"officialTitle":621,"acronym":622,"eligibilityCriteria":623,"healthyVolunteers":11,"sex":17,"minAge":624,"maxAge":361,"enrollmentInfo":625,"targetDuration":4,"studyType":251,"phases":4,"briefSummary":627,"conditions":628,"keywords":4,"overallStatus":257,"whyStopped":4,"lastUpdateSubmitDate":630,"lastUpdatePostDateStruct":631,"startDateStruct":633,"completionDateStruct":635,"leadSponsor":637,"locationsCount":4},"100540942","integrated-analysis-of-therapy-response-and-resistence-in-embryonal-tumors-and-gliomas-100540942","NCT06323408","Integrated Analysis of Therapy Response and Resistence in Embryonal Tumors and Gliomas","Prospective Collection of Clinical and Imaging Data, Radiotherapy Planning and Biomaterials for Integrated Analysis of Therapy Response and Resistance and Detection of Molecular Targets in Adolescents and Young Adults With CNS Tumors","BZKF-AYA","Inclusion Criteria:\n\n1. first diagnosis of high-risk CNS tumors including glioma IDHmutated, medulloblastoma, ependymoma and other intra-axial primary brain tumors\n2. adolescents and young adults (AYA; 15 to 39 years)\n3. Karnofsky status of 60 or higher\n4. resection, extended biopsy or stereotactic biopsy with sufficient tissue volume\n5. multimodal therapy planned at the discretion of the treating specialist\n6. expected survival time of at least 6 months\n7. informed consent from the patient or the patient's legal guardian prior to the first study procedure\n8. complete material collection expected.\n\nExclusion Criteria:\n\n1. synchronous independent tumor disease other than basal cell carcinoma and carcinoma in situ\n2. participation in interventional clinical trial except in standard arms of interventional clinical trials.","15 Years",{"count":626,"type":22},72,"The treatment of adolescents and young adults (AYA, 15 to 39 years) with malignant intra-axial CNS parenchymal tumors such as IDH-mutated gliomas, medulloblastomas and ependymomas is still not curative in all cases. The tumor biology and clinical needs to diagnose and treat these tumors are comparable across all age groups, so an integrated treatment environment overseen by adult and pediatric neuro-oncology specialists seems promising to leverage synergisms and advance diagnostic and therapeutic development in these tumors. A comprehensive, prospective and integrated biomaterial and imaging-based pipeline for the multi-faceted evaluation of AYAs has not yet been established for AYA patients with brain tumors in Germany. Current diagnostic platforms neglect the integrative processing of data from MRI and FET-PET imaging, radiotherapy plans, tumor tissue, liquid biopsies and clinical data as well as prognostic markers. A prospective AYA pipeline can therefore enable a better understanding of the aforementioned high-risk CNS malignancies and promises clinical advances for AYA patients and the clinical and scientific research landscape.",[629,545,31,32],"Glioma, Malignant","2025-03-24",{"date":632,"type":48},"2025-03-25",{"date":634,"type":22},"2025-05",{"date":636,"type":22},"2026-03",{"name":638,"class":55},"University Hospital Regensburg",{"id":640,"slug":641,"hasResults":11,"nctId":642,"briefTitle":643,"officialTitle":643,"acronym":4,"eligibilityCriteria":644,"healthyVolunteers":11,"sex":17,"minAge":218,"maxAge":4,"enrollmentInfo":645,"targetDuration":597,"studyType":251,"phases":4,"briefSummary":647,"conditions":648,"keywords":4,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":656,"lastUpdatePostDateStruct":657,"startDateStruct":659,"completionDateStruct":661,"leadSponsor":663,"locationsCount":56},"100412277","proton-therapy-research-infrastructure--protrait--neuro-oncology-100412277","NCT04648462","Proton Therapy Research Infrastructure- ProTRAIT- Neuro-oncology","Inclusion Criteria:\n\n1. All brain tumors with a favorable prognosis (median survival \\> 10 year)\n2. Age ≥ 18 years\n3. ECOG performance status 0 - 1 \u002F Karnofsky performance status 80 - 100\n4. No - minimal neurocognitive impairment\n5. Dosimetrical gain of protontherapy relative to photontherapy (≥5% on supratentorial brain dose or hippocampi)\n6. Informed consent\n\nExclusion Criteria:\n\n1. Not eligible for chemotherapy\n2. Eligible for stereotactic radiotherapy",{"count":646,"type":22},1500,"The first proton therapy treatments in the Netherlands have taken place in 2018. Due to the physical properties of protons, proton therapy has tremendous potential to reduce the radiation dose to the healthy, tumour-surrounding tissues. In turn, this leads to less radiation-induced complications, and a decrease in the formation of secondary tumours. The Netherlands has spearheaded the development of the model-based approach (MBA) for the selection of patients for proton therapy when applied to prevent radiation-induced complications. In MBA, a pre-treatment in-silico planning study is done, comparing proton and photon treatment plans in each individual patient, to determine (1) whether there is a significant difference in dose in the relevant organs at risk (ΔDose), and (2) whether this dose difference translates into an expected clinical benefit in terms of NormalTissue Complication Probabilities (ΔNTCP). To translate ΔDose into ΔNTCP, NTCP-models are used, which are prediction models describing the relation between dose parameters and the likelihood of radiation-induced complications. The Dutch Society for Radiotherapy and Oncology (NVRO) setup the selection criteria for proton therapy in 2015, taking into account toxicity and NTCP. However, NTCP-models can be affected by changes in the irradiation technique. Therefore, it is paramount to continuously update and validate these NTCP-models in subsequent patient cohorts treated with new techniques. In ProTRAIT, a Findable, Accessible, Interoperable and Reusable (FAIR)data infrastructure for both clinical and 3D image and 3D dose information has been developed and deployed for proton therapy in the Netherlands. It allows for a prospective, standardized, multi-centric data from all Dutch proton and a representative group of photon therapy patients.",[649,32,650,504,651,104,652,653,654,546,255,655],"Astrocytoma","Ganglioglioma","Optic Nerve Glioma","Nerve Sheath Neoplasms","Adenoma","Craniopharyngioma","Neurilemmoma","2024-11-25",{"date":658,"type":48},"2024-11-26",{"date":660,"type":48},"2018-01-01",{"date":662,"type":22},"2035-01-01",{"name":664,"class":55},"Maastricht Radiation Oncology",{"id":666,"slug":667,"hasResults":11,"nctId":668,"briefTitle":669,"officialTitle":670,"acronym":671,"eligibilityCriteria":672,"healthyVolunteers":11,"sex":17,"minAge":64,"maxAge":673,"enrollmentInfo":674,"targetDuration":4,"studyType":251,"phases":4,"briefSummary":676,"conditions":677,"keywords":4,"overallStatus":257,"whyStopped":4,"lastUpdateSubmitDate":678,"lastUpdatePostDateStruct":679,"startDateStruct":681,"completionDateStruct":683,"leadSponsor":685,"locationsCount":86},"100554480","in-vitro-models-from-pediatric-brain-tumors-100554480","NCT06499636","In Vitro Models From Pediatric Brain Tumors","In Vitro Models Derived From Pediatric Glial Tumors and Pediatric Embryonal Tumors for Drug Testing and Molecular Studies","PBTS23","Inclusion Criteria:\n\n* Children and young adults who undergo standard surgical resection for suspected primary brain tumors or recurrent brain tumors\n* signed written informed consent\n\nExclusion Criteria:\n\n* no informed consent","35 Years",{"count":675,"type":22},100,"Tumors of the Central Nervous System (CNS) represent the leading cause of cancer-related deaths in children. Current treatment options are not curative for most malignant histologies, and intense preclinical and clinical research are necessary to develop more effective therapeutic interventions against these tumors, most of which meet the FDA definition for orphan diseases. The majority of malignant CNS tumors in children and adolescents belong to two broad histologic tumor entities: those of glial origin, such as high-grade glioma (HGG)and ependymoma (EPN), and those of neuronal origin, also identified as embryonal tumors, that include medulloblastoma and AT\u002FRT(1). Over the last few years, whole-genome sequencing, gene-expression profiling and genome-wide methylation studies have greatly deepened our understanding of the biology and genetics of these tumors, allowing for robust stratification in clinically relevant molecular subgroups. The advancement of single-cell omics over the last decade have highlighted the enormous heterogeneity of tumors, a complex mixture of co-existing cancer subclones and supportive normal cell populations.\n\nHowever, current treatments have remained largely static, and 5-year survival rate for children with malignant CNS tumors only achieves a modest 57.5%.\n\nMore effective treatment strategies should include novel chemotherapeutic agents that take into account high intrinsic tumor heterogeneity as well as the complex regulations of transcriptional and translational mechanisms that control protein expression. Identification of novel drugs and treatment strategies is further limited by the paucity of appropriate preclinical models, which mirror the molecular characteristics of distinct tumor subgroups.\n\nWe propose to establish patient-derived in vitro models to predict chemotherapeutic drug sensitivity\u002Fresistance in malignant pediatric CNS tumors. Next, we propose to perform molecular analyses in tissues of pediatric CNS tumors to determine whether in vitro findings have clinical correlates.",[629,32,31],"2024-07-08",{"date":680,"type":48},"2024-07-12",{"date":682,"type":22},"2024-09-01",{"date":684,"type":22},"2029-06-30",{"name":686,"class":55},"Fondazione Policlinico Universitario Agostino Gemelli IRCCS",{"id":688,"slug":689,"hasResults":11,"nctId":690,"briefTitle":691,"officialTitle":692,"acronym":693,"eligibilityCriteria":694,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":695,"targetDuration":4,"studyType":23,"phases":696,"briefSummary":697,"conditions":698,"keywords":4,"overallStatus":257,"whyStopped":4,"lastUpdateSubmitDate":699,"lastUpdatePostDateStruct":700,"startDateStruct":702,"completionDateStruct":704,"leadSponsor":706,"locationsCount":4},"100553424","phase-1-axitinib-and-oral-metronomic-etoposide-for-pediatric-children-and-aya-refractoryrelapsing-medulloblastoma-and-ependymoma-100553424","NCT06485908","Axitinib and Oral Metronomic Etoposide for Pediatric Children and AYA Refractory\u002FRelapsing Medulloblastoma and Ependymoma","MEPENDAX: Phase I\u002FII Study of Axitinib (Inlyta®) and Oral Metronomic Etoposide for Pediatric Children and AYA Refractory\u002FRelapsing Medulloblastoma and Ependymoma","MEPENDAX","Inclusion Criteria:\n\n* Histologically proven diagnosis of ependymoma or medulloblastoma\n* Methyloma classification performed or available material for methyloma analysis\n* Confirmed progressive or refractory disease despite standard therapy, or for which no effective standard therapy exists\n* Male and female subjects with \\> 4 to ≤ 25 years of age at inclusion\n* Weight \\> 20 kg\n* Evaluable target lesion(s) according to RAPNO\n* Performance status: Karnofsky performance status (for patients \\>12 years of age) or Lansky Play score (for patients ≤12 years of age) ≥ 70%. Patients who are unable to walk because of paralysis or stable neurological disability, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score\n* Life expectancy ≥ 3 months\n* No known allergy to any of the compounds in the experimental treatment\n* Able to take oral treatments\n* Adequate organ function:\n\nHematologic criteria\n\n* Peripheral absolute neutrophil count (ANC) ≥ 1000\u002Fmm3 (unsupported)\n* Platelet count ≥ 100,000\u002Fmm3 (unsupported)\n* Hemoglobin ≥ 8.0 g\u002FdL (transfusion is allowed) Cardiac function\n* Shortening fraction (SF) \\>29% and left ventricular ejection fraction (LVEF) ≥50% at baseline, as determined by echocardiography (mandatory only for patients who have received cardiotoxic therapy).\n\nRenal and hepatic function\n\n* Serum creatinine \\\u003C 1.5 x upper limit of normal (ULN) for age\n* Total bilirubin \\\u003C 1.5 x ULN\n* Alanine aminotransferase (ALT)\u002F Aspartate aminotransferase (AST)\u002F \\\u003C 2.5 x ULN\n\n  * Able to comply with scheduled follow-up and with management of toxicity.\n  * Females of child bearing potential must have a negative serum pregnancy test within 7 days prior to initiation of treatment.\n  * Sexually active patients must agree to use adequate and appropriate contraception (in accordance with Clinical Trials Facilitation and Coordination Group (CTFG) recommendations) while on study drug and for 6 months after stopping the study drug.\n  * Patient able to comfortably swallow capsules.\n  * Written informed consent from parents\u002Flegal representative, patient, and age-appropriate assent before any study-specific screening procedures are conducted according to local, regional or national guidelines.\n  * Patient affiliated to a social security regimen or beneficiary of the same according to local requirements.\n\nNon-inclusion Criteria\n\n* Chemotherapy within 21 days of day 1 from the start of study treatment. This period can be shortened in the case of treatment with vincristine (2 weeks) and extended to 6 weeks in the case of treatment with nitrosureas. The period is set to 5 half-lives in the case of targeted therapies or metronomic chemotherapy. The period is set to 2 weeks after bevacizumab administration. Evidence of \\> Grade 1 recent CNS hemorrhage on the baseline MRI or scan.\n* Impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).\n* Clinically significant, uncontrolled heart disease (including history of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening).\n* Known active viral hepatitis or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection.\n* Presence of any NCI-CTCAE v5 grade ≥ 2 treatment-related extra-hematological toxicity with the exception of alopecia, ototoxicity or peripheral neuropathy.\n* Known congenital immunodeficiency.\n* Radiotherapy within the 2 months preceding D1 of the start of study treatment. Palliative RT on a non-target lesion is allowed up to 1 weeks before beginning of treatment.\n* Major surgery within 21 days of the first dose. Gastrostomy, ventriculo-peritoneal shunt, endoscopic ventriculostomy, tumor biopsy and insertion of central venous access devices are not considered major surgery, but for these procedures, a 48 hour interval must be maintained before the first dose of the investigational drug is administered.\n* Bleeding disorder.\n* Clinically significant, uncontrolled heart disease (including history of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening).\n* Known hypersensitivity to any study drug or component of the formulation.\n* Absence of effective contraception in patients of childbearing age (see appendix 3)\n* Pregnant or nursing (lactating) females.\n* Patients with galactose intolerance, lactase deficiency or glucose or galactose malabsorption syndrome (rare hereditary diseases).\n* Severe infections requiring parenteral antibiotic therapy.\n* Inability to undergo medical monitoring of the trial for geographic, social or psychological reasons.",{"count":331,"type":22},[25,26],"It is an open multicentric phase I\u002FII trial with axitinib (Inlyta®) and metronomic delivery of etoposide for children, adolescent and young adults (AYA) with refractory\u002F relapsing solid tumors. It is a two-stage trial:\n\nFirst stage: To determine the Maximum Tolerated Dose (MTD) of the combination of axitinib and oral metronomic etoposide for patient with medulloblastoma or ependymoma Second stage: Extension cohort evaluating the preliminary efficacy at the recommended dose for the phase II (RDP2) of the combination. The 2nd stage will start after a meeting of independent data monitoring committee (IDMC). Two cohorts of 9 patients with ependymoma and medulloblastoma Patients treated at first stage won't be included in the second stage.",[31,32],"2024-07-02",{"date":701,"type":48},"2024-07-03",{"date":703,"type":22},"2024-10",{"date":705,"type":22},"2030-01",{"name":707,"class":55},"Assistance Publique Hopitaux De Marseille",{"id":709,"slug":710,"hasResults":11,"nctId":711,"briefTitle":712,"officialTitle":713,"acronym":714,"eligibilityCriteria":715,"healthyVolunteers":11,"sex":17,"minAge":716,"maxAge":218,"enrollmentInfo":717,"targetDuration":597,"studyType":251,"phases":4,"briefSummary":719,"conditions":720,"keywords":722,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":724,"lastUpdatePostDateStruct":725,"startDateStruct":727,"completionDateStruct":729,"leadSponsor":731,"locationsCount":86},"100490893","genetic-and-molecular-risk-profiles-of-pediatric-malignant-brain-tumors-in-china-100490893","NCT05672043","Genetic and Molecular Risk Profiles of Pediatric Malignant Brain Tumors in China","Perspective Study on Genetic Predispositions and Clinical Prognosis of Children and Adolescents With Malignant Brain Neoplasms in China","GRIPP","Inclusion Criteria:\n\n\\- Children and adolescents aged between 0-18 years old, diagnosed with medulloblastoma or other malignant central nervous system tumors including glioma, ependymoma, germ cell tumors,tuberous sclerosis, neuronal and neuronoglial tumors, choroid plexus tumors, atypical teratoid\u002Frhabdoid tumors, ependymoblastoma, and medulloepithelioma;\n\nPatients must be eligible for and receive tumor resection;\n\nHistological examination by institutional neuro-pathological evaluation must confirmed the diagnosis of brain malignancies;\n\nParticipants consent with joining the current study and comply with follow-up visits;\n\nThe patients must have no previous radiotherapy or chemotherapy other than corticosteroids.\n\nExclusion Criteria:\n\n\\- Patients with major perioperative complications which lead to significant and sudden deterioration;\n\nPatients with major systemic illness (e.g., serious infection or significant cardiac, pulmonary, hepatic, or other organ dysfunction) which might compromise the patient's ability to tolerate standard treatment or would likely interfere with overall prognosis;\n\nPatients with major adverse events or sudden deterioration irrelevant to the current study;\n\nQuality of tumor tissue sample did not meet the criterion for genetic sequencing and laboratory investigations;\n\nPatients who refuse to participate in the study or who request dropping out from the study","0 Years",{"count":718,"type":22},400,"Primary malignant central nervous system (CNS) tumors are the second most common childhood malignancies. Amongst, medulloblastomas are the most common malignant brain tumor of childhood and occur primarily in the cerebellum. According to molecular characteristics, medulloblastomas were classified into four subtypes: WNT, SHH, Group3 and Group4 and different prognosis were noticed between subgroups. Several genetic predispositions related to clinical outcome were also discovered and might influence the treatment of medulloblastomas as novel pharmaceutical targets. This study aims to investigate genetic and cellular profiles of pediatric brain malignancies, mostly medulloblastomas, and other central nervous system tumor based on WGS, RNA-seq, single-cell sequencing and spatial transcriptomics. We also aim to investigate the correlation between genetic characteristics and clinical prognosis.",[31,721,32,399,225,428],"Central Nervous System Tumor, Pediatric",[471,723],"pediatric brain tumor","2023-01-03",{"date":726,"type":48},"2023-01-05",{"date":728,"type":48},"2023-01-01",{"date":730,"type":22},"2032-12-31",{"name":732,"class":55},"Beijing Tiantan Hospital"]