[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"medulloblastoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:medulloblastoma":30},{"pageToken":4,"total":5,"offset":6,"count":7,"results":8},null,29,0,25,[9,52,75,108,138,171,210,242,263,286,349,371,395,426,456,490,508,549,584,620,664,685,724,751,776],{"id":10,"slug":11,"hasResults":12,"nctId":13,"briefTitle":14,"officialTitle":15,"acronym":4,"eligibilityCriteria":16,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":20,"targetDuration":4,"studyType":23,"phases":24,"briefSummary":27,"conditions":28,"keywords":33,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":41,"startDateStruct":44,"completionDateStruct":46,"leadSponsor":48,"locationsCount":51},"100528495","plx038-in-primary-central-nervous-system-tumors-containing-myc-or-mycn-amplifications-100528495",false,"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 must be confirmed by documented history. Participants who do not have documented history will be tested 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 (if necessary) 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).\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 unresolved or persistent grade 2 or higher GI toxicity from any type of RT at screening\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.","ALL","18 Years","120 Years",{"count":21,"type":22},146,"ESTIMATED","INTERVENTIONAL",[25,26],"PHASE1","PHASE2","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.",[29,30,31,32],"Glioma","Medulloblastoma","Ependymoma","Glioblastoma",[34,35,36,37,38],"Brain Tumors","Recurrent or progressive primary CNS tumors","Patient-Reported Outcomes","Spine Tumors","MYC or MYCN genes","RECRUITING","2026-08-11",{"date":42,"type":43},"2026-08-12","ACTUAL",{"date":45,"type":43},"2024-01-31",{"date":47,"type":22},"2033-11-14",{"name":49,"class":50},"National Cancer Institute (NCI)","NIH",1,{"id":53,"slug":54,"hasResults":12,"nctId":55,"briefTitle":56,"officialTitle":57,"acronym":4,"eligibilityCriteria":58,"healthyVolunteers":12,"sex":17,"minAge":4,"maxAge":59,"enrollmentInfo":60,"targetDuration":4,"studyType":23,"phases":62,"briefSummary":63,"conditions":64,"keywords":4,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":65,"lastUpdatePostDateStruct":66,"startDateStruct":67,"completionDateStruct":69,"leadSponsor":71,"locationsCount":74},"100415929","phase-2-dfmo-as-maintenance-therapy-for-molecular-highvery-high-risk-and-relapsed-medulloblastoma-100415929","NCT04696029","DFMO as Maintenance Therapy for Molecular High\u002FVery High Risk and Relapsed Medulloblastoma","Phase II Trial of Eflornithine\u002FDFMO as Maintenance Therapy for Molecular High Risk\u002FVery High Risk and Relapsed\u002FRefractory Medulloblastoma","Inclusion Criteria:\n\n1. Age: 0-21 years of age at diagnosis\n2. Pathology All patients must either have a pathologically confirmed diagnosis of medulloblastoma with molecular grouping identified by either Nanostring or methylation profiling.\n\n   Cohort 1- Molecular High Risk:\n   * Metastatic non-MYC amplified Group 3\n   * Metastatic Group 4\n   * Metastatic non-WNT\u002Fnon-SHH (Must be non-MYC amplified)\n\n   Cohort 2- Molecular Very High Risk\n   * Metastatic OR MYCN amplified OR TP53 mutant non-infant (\\>3 yrs) SHH\n   * MYC amplified Group 3\n   * Non-WNT, non-SHH infant (\\\u003C 3 yrs)\n\n   Cohort 3: Relapsed\u002FRefractory Medulloblastoma\n3. Pre-enrollment tumor survey:\n\n   Prior to enrollment on this study, a determination of mandatory disease staging must be performed:\n   * Tumor imaging studies including: Brain and spine MRI\n   * Lumbar Puncture only if previously positive\n   * Bone Marrow aspiration\u002Fbiopsy only if previously positive\n   * This disease assessment is required for eligibility and preferably should be done within 2 weeks prior to first dose of study drug, but must be done within a maximum of 4 weeks before first dose of study drug.\n4. Disease Status: Subjects must have no evidence of disease, or stable\\* residual nonbulky\\*\\* disease.\n\n   \\*Stable residual disease defined as non-progression over 2 separate imaging studies at least 6 weeks apart\n\n   \\*\\*Non-bulky disease defined as maximal cross-sectional area \\\u003C 3cm\\^2 at enrollment. Patients with leptomeningeal disease are allowed to participate on study.\n5. Timing from prior therapy:\n\n   Enrollment (first dose of DFMO) no later than 60 days after last dose of conventional chemotherapy. Patients who have undergone high dose chemotherapy (HDCT) with autologous stem cell transplantation (SCT) are eligible if more than 45 days have elapsed since date of last SCT.\n6. Patients must have a Lansky or Karnofsky Performance Scale score of ≥ 50% (see Appendix II) and patients must have a life expectancy of ≥ 2 months.\n7. All clinical and laboratory studies for organ functions to determine eligibility must be performed within 7 days prior to first dose of study drug unless otherwise indicated below.\n8. Patients must have adequate organ functions at the time of registration:\n\n   * Hematological: Hematological recovery as defined by ANC ≥750\u002FμL, platelets ≥30 (non-transfused x 7 days)\n   * Liver: Adequate liver function as defined by AST and ALT \\\u003C10x upper limit of normal\n   * Renal: Adequate renal function defined as (perform one of the following): Creatinine clearance or radioisotope GFR ≥ 70 mL\u002Fmin\u002F1.73 m2 or a serum creatinine based on age\u002Fgender\n9. Females of childbearing potential must have a negative pregnancy test. Patients of childbearing potential must agree to use an effective birth control method. Female patients who are lactating must agree to stop breast-feeding.\n10. Written informed consent in accordance with institutional and FDA guidelines must be obtained from all subjects (or patients' legal representative).\n\nExclusion Criteria:\n\n1. BSA of \\\u003C0.25 m2\n2. Metastatic disease outside of CNS\n3. Relapsed\u002Frefractory patients who are radiation-naïve and age 5 years or older at time of enrollment\n4. Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.\n5. Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from the hematological and bone marrow suppression effects of prior chemotherapy.\n6. Infection: Subjects who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.\n7. Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.","21 Years",{"count":61,"type":22},118,[26],"Difluoromethylornithine (DFMO) will be used in an open label, multicenter, study as Maintenance Therapy for Molecular High Risk\u002FVery High Risk and Relapsed\u002FRefractory Medulloblastoma.",[30],"2026-08-10",{"date":42,"type":43},{"date":68,"type":43},"2021-03-29",{"date":70,"type":22},"2029-03",{"name":72,"class":73},"Giselle Sholler","OTHER",26,{"id":76,"slug":77,"hasResults":12,"nctId":78,"briefTitle":79,"officialTitle":80,"acronym":81,"eligibilityCriteria":82,"healthyVolunteers":12,"sex":17,"minAge":83,"maxAge":84,"enrollmentInfo":85,"targetDuration":4,"studyType":23,"phases":87,"briefSummary":89,"conditions":90,"keywords":95,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":99,"lastUpdatePostDateStruct":100,"startDateStruct":101,"completionDateStruct":103,"leadSponsor":105,"locationsCount":107},"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":86,"type":22},74,[88],"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.",[30,91,92,31,93,94],"Medulloblastoma, Childhood","Medulloblastoma Recurrent","Ependymoma Malignant","Ependymoma of Brain",[96,97,98],"Individualized Treatment Plan","Genetic Screening","Screening","2026-08-07",{"date":40,"type":43},{"date":102,"type":43},"2022-02-22",{"date":104,"type":22},"2028-01-31",{"name":106,"class":73},"University of California, San Francisco",9,{"id":109,"slug":110,"hasResults":12,"nctId":111,"briefTitle":112,"officialTitle":112,"acronym":113,"eligibilityCriteria":114,"healthyVolunteers":12,"sex":17,"minAge":115,"maxAge":116,"enrollmentInfo":117,"targetDuration":4,"studyType":23,"phases":119,"briefSummary":120,"conditions":121,"keywords":125,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":128,"lastUpdatePostDateStruct":129,"startDateStruct":131,"completionDateStruct":133,"leadSponsor":135,"locationsCount":137},"100564069","phase-1-atovaquone-combined-with-radiation-in-children-with-malignant-brain-tumors-100564069","NCT06624371","Atovaquone Combined With Radiation in Children With Malignant Brain Tumors","AflacBT2303","Inclusion Criteria:\n\n-Stratum 1\n\n* Newly diagnosed pHGG\u002FDMG\u002FDIPG Patients must have histologically confirmed pediatric high-grade glioma (pHGG, WHO Grade 3 or 4) or diffuse midline glioma with altered H3K27 (DMG, WHO Grade 4). Primary pHGG or DMG spinal tumors are eligible. Diffuse intrinsic pontine glioma (DIPG) defined by MRI does not require histological confirmation.\n* Weight \\> 10kg\n* Karnofsky and Lansky performance score \\> 50%\n* Patients with stable seizures (e.g., no seizures for ≥ 7 days and not requiring escalation or addition of anti-epileptic drugs) will be eligible.\n* Adequate liver function defined as:\n\n  * Total bilirubin ≤ 2x upper limit of normal (ULN) and\n  * AST (SGOT) and ALT (SGPT) ≤ 225 U\u002FL (5x the ULN). The ULN for AST and ALT will be 45 U\u002FL.\n* Patients must have normal organ and marrow function as defined below:\n\n  * absolute neutrophil count \\> 1,000\u002FmcL\n  * platelets \\> 100,000\u002FmcL\n  * hemoglobin \\> 8g\u002FdL\n  * Total bilirubin within normal institutional limits\n  * AST(SGOT)\u002FALT(SGPT) \\\u003C 5 x (\\\u003C10 x if taking steroids) the institutional upper limit of normal\n  * creatinine within normal institutional limits for age 2 OR\n  * creatinine clearance \\> 60mL\u002Fmin\u002F1.73 m for patients with creatinine levels above institutional normal\n\nStratum 2\n\n* Relapsed, progressive pHGG\u002FDMG\u002FDIPG and medulloblastoma (MB) or pHGG\u002FDMG\u002FDIPG after completion of standard radiation therapy without prior atovaquone exposure and before progression. Patients with metastatic disease are allowed for Stratum 2 only.\n\n  --Measurable disease is not necessary for enrollment study.\n* Patients must have previously undergone standard-of-care treatment including surgery, radiation, and\u002For first-line adjuvant chemotherapy before the experimental treatment (atovaquone).\n* Patients must have recovered from the acute treatment-related toxicities (defined as \\\u003C grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy or radiotherapy prior to entering this study. There is no upper limit to the number of prior therapies that is allowed.\n* Age \\> 2 to 25 years\n* Weight \\> 10kg\n* Karnofsky and Lansky performance score \\> 50%\n* Patients with stable seizures (e.g., no seizures for ≥ 7 days and not requiring escalation or addition of anti-epileptic drugs) will be eligible.\n* Patients must have normal organ and marrow function as defined above for Stratum 1\n* Adequate liver function is defined as:\n\n  1. Total bilirubin ≤ 2x upper limit of normal (ULN) and\n  2. AST (SGOT) and ALT (SGPT) ≤ 225 U\u002FL (5x the ULN). The ULN for AST and ALT will be 45 U\u002FL.\n\nExclusion Criteria:\n\nStratum 1\n\n* Chronic systemic concurrent illness\n* Concurrent or history of anti-cancer therapy other than RT\n* Patients with metastatic tumor are excluded for Stratum 1 only.\n* Patients with uncontrolled seizures or seizure requiring escalation or addition of anti-epileptic drugs are excluded.\n* Patients must fully recover from all acute effects of prior surgical intervention.\n* History of allergic reactions to atovaquone or attributed to compounds of similar chemical or biological composition to atovaquone.\n* Symptomatic intratumoral hemorrhage, or asymptomatic intratumoral hemorrhage larger than punctate foci, at any time prior to enrollment.\n* Pregnant or breast-feeding women will not be entered into this study as there may be fetal risks or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during treatment and for 3 months after stopping treatment. This should be documented in the electronic medical records as part of the consent discussion.\n\nStratum 2\n\n* Concurrent illness\n* Patients must have recovered from all prior therapy as follows:\n\n  1. Patients must have received their last dose of known myelosuppressive anticancer therapy at least three (3) weeks before study enrollment or at least six (6) weeks if prior nitrosourea.\n  2. Biologic or investigational agent (anti-neoplastic): Patient must have received their last dose of the investigational or biologic agent ≥ 7 days before study enrollment.\n  3. Antibodies: ≥ 21 days must have elapsed from an infusion of the last dose of antibody and toxicity related to prior antibody therapy must be recovered to Grade ≤ 1. Agents with prolonged half-lives: At least three half-lives must have elapsed before enrollment.\n  4. Immunotherapy: Patient must have completed immunotherapy (e.g. tumor vaccines, oncolytic viruses. etc.) at least 42 days before enrollment.\n  5. Radiation: Patients must have had their last fraction of • Craniospinal irradiation ≥ 3 months before enrollment. • Other substantial bone marrow irradiation ≥ 6 weeks before enrollment • Local or palliative XRT (small port) ≥ 2 weeks.\n  6. Stem Cell Transplant: Patient must be ≥ 12 weeks since autologous bone marrow\u002Fstem cell transplant before enrollment. Patients with uncontrolled seizures or seizure requiring escalation or addition of anti-epileptic drugs are excluded.\n* Patients must fully recover from all acute effects of prior surgical intervention.\n* History of allergic reactions to atovaquone or attributed to compounds of similar chemical or biological composition to atovaquone.\n* Pregnant or breast-feeding women will not be entered into this study as there may be fetal risks or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during treatment and for 3 months after stopping treatment. This should be documented in the electronic medical records as part of the consent discussion.","2 Years","25 Years",{"count":118,"type":22},18,[25],"The goal of this interventional study is to Assess the safety and tolerability of atovaquone in combination with standard radiation therapy (RT) for the treatment of pediatric patients with newly diagnosed pediatric high-grade glioma\u002Fdiffuse midline glioma\u002Fdiffuse intrinsic pontine glioma (pHGG\u002FDMG\u002FDIPG).\n\nThe secondary aim is to assess the safety and tolerability of longer-term atovaquone treatment for pediatric patients with relapsed or progressed pHGG\u002FDMG\u002FDIPG and medulloblastoma (MB) or pHGG\u002FDMG\u002FDIPG after completion of RT and before progression.",[122,30,123,124],"High-grade Glioma","Diffuse Intrinsic Pontine Glioma","Diffuse Midline Glioma, H3 K27M-Mutant",[126,127],"Atovaquone","Progression-free survival","2026-07-30",{"date":130,"type":43},"2026-08-03",{"date":132,"type":43},"2025-03-28",{"date":134,"type":22},"2027-10",{"name":136,"class":73},"Emory University",2,{"id":139,"slug":140,"hasResults":12,"nctId":141,"briefTitle":142,"officialTitle":143,"acronym":4,"eligibilityCriteria":144,"healthyVolunteers":12,"sex":17,"minAge":145,"maxAge":146,"enrollmentInfo":147,"targetDuration":4,"studyType":149,"phases":4,"briefSummary":150,"conditions":151,"keywords":155,"overallStatus":161,"whyStopped":4,"lastUpdateSubmitDate":162,"lastUpdatePostDateStruct":163,"startDateStruct":165,"completionDateStruct":167,"leadSponsor":169,"locationsCount":4},"100645498","ai-assisted-mri-molecular-subtyping-in-pediatric-brain-tumors-100645498","NCT07703605","AI-Assisted MRI Molecular Subtyping in Pediatric Brain Tumors","AI-Assisted Presurgical MRI Molecular Subtyping for Pediatric Brain Tumors: A Single-Center Ambispective Clinical Cohort Study","Inclusion Criteria:\n\n* Age younger than 18 years at the time of index surgery.\n* Evaluated at a participating study center and scheduled for first surgical treatment of a suspected target pediatric brain tumor.\n* Preoperative brain MRI available before surgery, including at minimum T1-weighted, contrast-enhanced T1-weighted, T2-weighted, and FLAIR sequences in DICOM format; MRI preferably performed within 7 days before surgery and before biopsy or tumor-directed therapy.\n* Postoperative histopathology confirming one of the following target tumor categories: glioma, medulloblastoma, ependymoma, atypical teratoid\u002Frhabdoid tumor, intracranial germ cell tumors, craniopharyngioma, or choroid plexus tumors.\n* For the prospective cohort, written informed consent provided by a parent or legal guardian, with child assent obtained when appropriate according to age, understanding, and local ethics requirements.\n\nExclusion Criteria:\n\n* Postoperative pathology confirming a non-target tumor type.\n* Recurrent tumor, repeat surgery, or prior tumor-directed surgery before the index surgery.\n* Preoperative MRI of inadequate quality for analysis, including severe motion artifact, severe susceptibility\u002Fmetal artifact, or incomplete field of view.\n* Prior biopsy, radiotherapy, chemotherapy, or other tumor-directed treatment before the index preoperative MRI that is judged to substantially affect imaging interpretation.\n* Concurrent malignant disease other than the target brain tumor.\n* Inability to comply with follow-up requirements in the prospective cohort, in the investigator's judgment, because of severe comorbidity or other practical limitations.","0 Years","17 Years",{"count":148,"type":22},1400,"OBSERVATIONAL","This multicenter observational cohort study aims to develop and validate an artificial intelligence (AI)-assisted diagnostic system for preoperative molecular subtyping of pediatric brain tumors using routine magnetic resonance imaging (MRI). The study will include seven major pediatric brain tumor categories: glioma, medulloblastoma, ependymoma, atypical teratoid\u002Frhabdoid tumor (AT\u002FRT), intracranial germ cell tumors, craniopharyngioma, and choroid plexus tumors.\n\nThe study includes a retrospective cohort for model development and internal\u002Fexternal validation, and a prospective cohort for further validation. Retrospective data will be collected from pediatric patients who underwent first surgical treatment between January 1, 2020 and December 31, 2025. Prospective enrollment will begin on July 15, 2026, with an anticipated sample size of 150 participants. The AI system will analyze preoperative MRI sequences, including T1-weighted, contrast-enhanced T1-weighted, T2-weighted, and FLAIR images, to predict key molecular markers and integrated diagnostic categories. The primary objective is to evaluate the diagnostic performance of the AI system for prespecified molecular prediction tasks using postoperative histopathology and molecular testing as the reference standard. Secondary objectives include assessing agreement with integrated diagnosis, comparing performance against blinded radiologists, and exploring prognostic associations of AI-predicted subgroups.",[152,29,30,31,153,154],"Pediatric Brain Tumors","Craniopharyngioma","Choroid Plexus Tumors",[156,157,158,159,160],"Artificial Intelligence","Molecular Subtyping","Diagnostic Performance","Deep Learning","Pediatric Neuro-Oncology","NOT_YET_RECRUITING","2026-07-21",{"date":164,"type":43},"2026-07-23",{"date":166,"type":22},"2026-07-15",{"date":168,"type":22},"2029-12-30",{"name":170,"class":73},"Huashan Hospital",{"id":172,"slug":173,"hasResults":12,"nctId":174,"briefTitle":175,"officialTitle":176,"acronym":4,"eligibilityCriteria":177,"healthyVolunteers":12,"sex":17,"minAge":178,"maxAge":84,"enrollmentInfo":179,"targetDuration":4,"studyType":23,"phases":181,"briefSummary":182,"conditions":183,"keywords":196,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":200,"lastUpdatePostDateStruct":201,"startDateStruct":203,"completionDateStruct":205,"leadSponsor":207,"locationsCount":209},"100460636","phase-1-lutathera-for-treatment-of-recurrent-or-progressive-high-grade-cns-tumors-100460636","NCT05278208","Lutathera for Treatment of Recurrent or Progressive High-Grade CNS Tumors","Phase I\u002FII Study of Lutathera in Patients With Recurrent and\u002For Progressive High-Grade Central Nervous System Tumors and Meningiomas That Demonstrate Uptake on DOTATATE PET","All participants must meet the following inclusion and exclusion criteria. No exceptions will be given. Imaging studies to establish eligibility must be done within three weeks prior to enrollment. All other clinical evaluations to establish eligibility (except for \\[68Ga\\]Ga-DOTATATE PET) must be done within 7 days prior to enrollment.\n\n1. Screening Criteria\n\n   1.1 Diagnosis Patient must have a diagnosis of primary high-grade CNS tumor (any histopathologic diagnosis that is WHO grade III-IV) or meningioma (any histologic grade) that is recurrent, progressive, or refractory. Note that patients with DIPG (based on radiographic\u002Fclinical diagnosis) who have undergone biopsy will be eligible with histologic diagnosis of grade II-IV infiltrating glioma. All tumors must have histologic verification either at the time of diagnosis or recurrence, except for patients meningioma who have not previously undergone biopsy or resection.\n\n   Note: Refractory disease is defined as the presence of persistent abnormality on conventional MRI that is further distinguished by histology (biopsy or sample of lesion) or advanced imaging, OR as determined by the treating physician and discussed with the primary investigator prior to enrollment.\n\n   1.2 Prior Therapy Patients must have recurred\u002Fprogressed following prior standard therapy for their tumor. Note: Patients with meningioma, atypical meningioma, or anaplastic meningioma must have received at least surgical resection or radiation.\n\n   1.3 Screening Consent Participant\u002Flegal guardian is willing to sign a screening consent for \\[68Ga\\]Ga-DOTATATE PET imaging. The screening consent is to be obtained according to institutional guidelines. Assent, when appropriate, will be obtained according to institutional guidelines.\n2. Eligibility Criteria\n\n   * Phase I Age Patient must be ≥ 4 and \\\u003C12 years of age at the time of enrollment. Disease Status: Patients who participate in the efficacy expansion cohort must have bi-dimensionally measurable disease, defined as at least one lesion that can be accurately measured in at least two dimensions Patients with measurable extraneural disease only are also eligible.\n   * Phase II Age Patient must be 12 to \\\u003C\u002F=39 years at the time of enrollment.\n3. Inclusion Criteria\n\n   3.1 Uptake on \\[68Ga\\]Ga-DOTATATE PET Patients must have uptake on DOTATATE PET\u002FCT in at least one tumor lesion (corresponding to known disease) equivalent to a Krenning score ≥2 (confirmed by central radiology review).\n\n   3.2 Prior Therapy Patients must have recovered from the acute treatment related toxicities (defined as ≤ grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy, radiotherapy, or any other treatment modality prior to entering this study.\n\n   3.3 Chemotherapy Patients must have received their last dose of known myelosuppressive anticancer therapy at least 21 days prior to enrollment or at least 42 days if nitrosourea.\n\n   3.4 Investigational\u002FBiologic Agent\n\n   ●Biologic or investigational agent (anti-neoplastic): Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the investigational or biologic agent ≥ 7 days prior to study enrollment.\n\n   For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur.\n\n   ●Monoclonal Antibodies and agents with known prolonged half-lives: Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the agent ≥ 28 days prior to study enrollment.\n\n   3.5 Radiation\n\n   Patients must have had their last fraction of:\n   * Craniospinal irradiation or total body irradiation or radiation to \\> 50% of pelvis \\> 3 months prior to enrollment.\n   * Focal irradiation \\> 4 weeks prior to enrollment\n\n   3.6 Stem Cell Transplant\n\n   Patient must be:\n   * ≥ 6 months since allogeneic stem cell transplant prior to enrollment with no evidence of active graft vs. host disease\n   * ≥ 3 months since autologous stem cell transplant prior to enrollment\n\n   3.7 Growth Factors Patients must be off all colony-forming growth factor(s) for at least 1 week prior to enrollment (e.g. filgrastim, sargramostim or erythropoietin). Two weeks must have elapsed if patients received long-acting formulations.\n\n   3.8 Thrombopoietin receptor agonist\n   * Phase I: Patients must be off thrombopoietin receptor agonists for at least 1 week prior to enrollment (e.g. romiplostim, eltrombopag)\n   * Phase II: Patients can receive concurrent thrombopoietin receptor agonists\n\n   3.9 Somatostatin analogs Patients must be off long-acting somatostatin analogs for at least 4 weeks and off short-acting somastatin analogs (i.e., octreotide) for at least 24 hours.\n\n   3.10 Neurologic Status\n   * Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment, documented by a detailed neurological exam.\n   * Patients with seizure disorders may be enrolled if seizures are well controlled.\n\n   3.11 Performance Status Karnofsky Performance Scale (KPS for \\> 16 years of age) or Lansky Performance Score (LPS for ≤ 16 years of age) assessed within two weeks of enrollment must be ≥ 50. Patients who are unable to walk because of neurologic deficits, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score\n\n   3.12 Organ Function\n\n   Patients must have adequate organ and marrow function, for eligibility and enrollment, as defined below:\n   * Adequate Bone Marrow Function as defined as:\n\n     * Absolute neutrophil count ≥ 1.0 x 109 cells\u002F L\n     * Platelets ≥100 x 109 cells\u002F L (unsupported, defined as no platelet transfusion within 7 days)\n     * Hemoglobin ≥8 g\u002Fdl (may receive transfusions)\n   * Adequate Renal Function as defined as:\n\n     * Creatinine clearance or radioisotope GFR \\>70mL\u002Fmin\u002F1.73m2 OR\n     * A serum creatinine based on (Schwartz et al. J. Peds, 106:522, 1985) age\u002Fgender as follows:\n\n       1 to \\\u003C 2 years: maximum serum creatinine 0.6 mg\u002FdL for males and females. 2 to \\\u003C 6 years: maximum serum creatinine 0.8 mg\u002FdL for males and females. 6 to \\\u003C 10 years: maximum serum creatinine 1.0 mg\u002FdL for males and females. 10 to \\\u003C 13 years: maximum serum creatinine 1.2 mg\u002FdL for males and females. 13 to \\\u003C 16 years: maximum serum creatinine 1.5 mg\u002FdL for males and 1.4 mg\u002FdL for females.\n\n       ≥ 16 years: maximum serum creatinine 1.7 mg\u002FdL for males and 1.4 mg\u002FdL for females.\n   * Adequate Liver Function as defined as:\n\n     * Total bilirubin ≤ 3 times institutional upper limit of normal (ULN) for age\n     * AST(SGOT)\u002FALT(SGPT) ≤ 3 times institutional ULN\n     * Serum albumin ≥ 2g\u002FdL\n     * Coagulation parameters: INR \\\u003C1.5 times ULN and aPTT \\\u003C1.5 times ULN unless patients are receiving therapeutic anticoagulation which affects these parameters\n   * Adequate Cardiac Function as defined as:\n\n     * Ejection fraction of ≥ 55% by echocardiogram\n     * Serum electrolytes (Sodium, Potassium, Chloride) within institutional limits of normal (patients can be on enteral supplementation)\n\n   3.13 Corticosteroids Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment, with a maximum dexamethasone dose of 2.5mg\u002Fm2\u002Fday.\n\n   3.14 Pregnancy Status Female patients of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.\n\n   3.15 Pregnancy Prevention Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study and for at least 7 months after drug cessation in females of childbearing potential and for at least 4 months after drug cessation in males of child fathering potential.\n\n   3.16 Informed Consent The patient or parent\u002Fguardian is able to understand the consent and is willing to sign a written informed consent document according to institutional guidelines.\n4. Exclusion Criteria\n\n   4.1 Confirmed bone marrow metastatic disease Patients with confirmed metastatic disease to bone marrow are ineligible.\n\n   4.2 Presence of bulky disease Patients with bulky disease on imaging as described below are ineligible. Treating physicians are encouraged to request a rapid central imaging review to confirm fulfillment of these criteria if there are questions or concerns.\n\n   Bulky disease is defined as:\n   * Tumor with evidence of clinically significant uncal herniation or midline shift.\n   * Tumor with diameter of \\>5cm in one dimension on T2\u002FFLAIR.\n   * Tumor that in the opinion of the site investigator shows significant mass effect in either the brain or spine.\n\n   Note that patients with metastatic or multi-focal disease (with exception of bone marrow) are eligible as long as no sites of disease meet above criteria for bulky disease.\n\n   4.3 Breast-feeding Nursing mothers are excluded from this study. There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Lutathera.\n\n   4.4 Concurrent Illness\n   * Patients with a history of any other malignancy, except patients with a secondary brain tumor if the patient's prior malignancy has been in remission for at least 5 years from the end of treatment.\n   * Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patient's ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results.\n   * Patients with type I diabetes.\n\n   4.5 Concomitant Medications\n   * Patients who are receiving any other anti-cancer or investigational drug therapy are ineligible.\n   * Prior or current treatment with 177Lu-DOTATATE\u002FTOC or 90Y-DOTATATE\u002FTOC.\n\n   4.6 Prisoners will be excluded from this study.\n\n   4.7 Inability to participate: Patients who in the opinion of the investigator are unwilling or unable to return for required follow-up visits, obtain follow-up studies required to assess toxicity to therapy, or adhere to drug administration plan, other study procedures, and study restrictions.\n5. Inclusion of Women and Minorities Both males and females of all races and ethnic groups are eligible for this study.","4 Years",{"count":180,"type":22},65,[25,26],"This study will evaluate the safety and efficacy of Lutathera (177Lu-DOTATATE) in patients with progressive or recurrent High-Grade Central Nervous System (CNS) tumors and meningiomas that demonstrate uptake on DOTATATE PET. The drug will be given intravenously once every 8 weeks for a total of up to 4 doses over 8 months in patients aged 4 to \\\u003C12 years (Phase I) or 12 to \\\u003C\u002F=39 years (Phase II) to test its safety and efficacy, respectively.\n\nFunding Source - FDA OOPD (grant number FD-R-0532-01)",[184,185,186,30,187,188,189,190,191,192,193,194,195],"High Grade Glioma","Meningioma","Embryonal Tumor","Anaplastic Ependymoma","Recurrent Diffuse Intrinsic Pontine Glioma","Recurrent Malignant Glioma","Recurrent Medulloblastoma","Recurrent Primary Central Nervous System Neoplasm","Refractory Diffuse Intrinsic Pontine Glioma","Refractory Malignant Glioma","Refractory Medulloblastoma","Refractory Primary Central Nervous System Neoplasm",[197,198,199],"Somatostatin Receptor","DOTATATE","Lutathera","2026-07-17",{"date":202,"type":43},"2026-07-20",{"date":204,"type":43},"2022-11-21",{"date":206,"type":22},"2033-11",{"name":208,"class":73},"Nationwide Children's Hospital",4,{"id":211,"slug":212,"hasResults":12,"nctId":213,"briefTitle":214,"officialTitle":215,"acronym":216,"eligibilityCriteria":217,"healthyVolunteers":12,"sex":17,"minAge":4,"maxAge":218,"enrollmentInfo":219,"targetDuration":4,"studyType":23,"phases":221,"briefSummary":222,"conditions":223,"keywords":224,"overallStatus":161,"whyStopped":4,"lastUpdateSubmitDate":233,"lastUpdatePostDateStruct":234,"startDateStruct":236,"completionDateStruct":238,"leadSponsor":240,"locationsCount":51},"100646102","targeting-myc-in-high-risk-medulloblastoma-100646102","NCT07694622","Targeting MYC in High-Risk Medulloblastoma","Exploiting High MYC Expression as a Potential Vulnerability for Treatment of High-Risk Medulloblastoma","MYCMB","Inclusion Criteria:\n\n* Patients with histologically confirmed Group 3 medulloblastoma (G3 MB)\n* Age between 0 and 20 years\n* Undergoing surgical treatment at the UOC Child Neurosurgery Unit, Fondazione Policlinico Universitario \"A. Gemelli\", IRCCS, Rome\n* Availability of tumor tissue obtained during standard-of-care surgical resection for molecular analyses and\u002For establishment of patient-derived organoids\n* Written informed consent provided by the patient and\u002For parent\u002Flegal guardian (prospective cohort)\n* Inclusion of retrospective cases in accordance with applicable Italian privacy regulations (Art. 110-bis)\n\nExclusion Criteria:\n\n* None","20 Years",{"count":220,"type":22},35,[88],"Medulloblastoma is the most common malignant brain tumor in children. Group 3 medulloblastoma (G3 MB) represents the most aggressive molecular subtype and is associated with poor prognosis, particularly in cases characterized by high expression or amplification of the MYC oncogene. Current treatment strategies are not tailored to this subgroup and are associated with significant long-term toxicities, highlighting the need for more specific therapeutic approaches.\n\nThis study aims to characterize biological processes and molecular pathways driven by high MYC expression in high-risk G3 medulloblastoma in order to identify potential therapeutic vulnerabilities. The study will investigate MYC-associated regulation of gene expression and RNA splicing in tumor cells and will define molecular dependencies that may be targeted using candidate or repurposed anticancer agents.\n\nTo achieve this, publicly available genomic datasets will be analyzed, findings will be validated in patient tumor specimens, and patient-derived three-dimensional (3D) tumor models will be established from surgical samples. These models will be used for ex vivo assessment of selected therapeutic strategies in a system that preserves key features of the original tumor.\n\nThis translational approach integrates computational analyses, molecular validation, and functional testing in patient-derived models to improve understanding of MYC-associated tumor biology in Group 3 medulloblastoma.",[30],[30,225,226,227,228,229,230,231,232],"Group 3 Medulloblastoma","MYC","RNA Splicing","Patient-Derived 3D Cultures","Gene Expression","MYC Amplification","Organoids","Transcriptomics","2026-07-03",{"date":235,"type":43},"2026-07-10",{"date":237,"type":22},"2026-09-01",{"date":239,"type":22},"2029-09-01",{"name":241,"class":73},"Fondazione Policlinico Universitario Agostino Gemelli IRCCS",{"id":243,"slug":244,"hasResults":12,"nctId":245,"briefTitle":246,"officialTitle":246,"acronym":4,"eligibilityCriteria":247,"healthyVolunteers":12,"sex":17,"minAge":4,"maxAge":4,"enrollmentInfo":248,"targetDuration":4,"studyType":149,"phases":4,"briefSummary":250,"conditions":251,"keywords":252,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":254,"lastUpdatePostDateStruct":255,"startDateStruct":257,"completionDateStruct":259,"leadSponsor":261,"locationsCount":51},"100599502","csimemphis-long-term-follow-up-of-medulloblastoma-survivors-that-received-craniospinal-irradiation-100599502","NCT07085325","CSIMEMPHIS: Long-term Follow-up of Medulloblastoma Survivors That Received Craniospinal Irradiation","Inclusion Criteria:\n\n* Diagnosis of any subtype of medulloblastoma between the ages of 3 to 22 years or between the ages of 22 to 44 years with the sonic hedgehog (SHH) subtype of medulloblastoma\n* Radiotherapy on or according to the SJMB12 protocol\n* Received radiotherapy at St. Jude Children's Research Hospital\n* 5 or more years since the initiation of radiation therapy and who did not have evidence of disease progression\n* Provision of informed consent by participant\u002Fguardian or legal representative; Assent by minor participant\n* Participants may choose to complete all or a subset of the proposed assessments; refusal to participate in some aspects of the study will not preclude participant inclusion\n* Participants must also complete enrollment on SJLIFE\n\nExclusion Criteria:\n\n* Participants or their legal guardian\u002Frepresentative are unwilling or unable to provide written informed consent.\n* Participants who had relapsed or refractory disease during or following completion of treatment for medulloblastoma",{"count":249,"type":22},184,"The study is being done to learn more about the long-term health and well-being of participants treated for medulloblastoma. The study is to decide which evaluations focusing on therapy-related lasting effects (or toxicities) should be considered.\n\nMedulloblastoma outcomes have improved with contemporary therapies including modern neurosurgical techniques and risk-adapted radiotherapy and chemotherapy regimens. However, survivors remain at risk for long-term health problems such as neurocognitive deficits, hearing loss, impaired cardiorespiratory fitness and physical performance, cardiac and neuroendocrine dysfunction, musculoskeletal conditions, and infertility.",[30],[30,253],"Survivor","2026-07-02",{"date":256,"type":43},"2026-07-06",{"date":258,"type":43},"2026-04-20",{"date":260,"type":22},"2031-10",{"name":262,"class":73},"St. Jude Children's Research Hospital",{"id":264,"slug":265,"hasResults":12,"nctId":266,"briefTitle":267,"officialTitle":268,"acronym":4,"eligibilityCriteria":269,"healthyVolunteers":12,"sex":17,"minAge":83,"maxAge":270,"enrollmentInfo":271,"targetDuration":4,"studyType":23,"phases":273,"briefSummary":274,"conditions":275,"keywords":4,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":254,"lastUpdatePostDateStruct":277,"startDateStruct":279,"completionDateStruct":281,"leadSponsor":283,"locationsCount":285},"100570020","phase-2-digoxin-medulloblastoma-study-100570020","NCT06701812","Digoxin Medulloblastoma Study","Evaluation of Digoxin for Relapsed Non-WNT, Non-SHH Medulloblastoma","Inclusion Criteria:\n\n* Patients must be age \\>12 months and \\\u003C30 years at the time of enrollment.\n* Patients must have relapsed non-WNT, non-SHH medulloblastoma confirmed by a CAP\u002FCLIA certified assay (such as nanostring or methylation) performed on tissue from diagnosis or relapse.\n* Patients must have received at least one prior course of chemotherapy for their medulloblastoma. They must also have received irradiation.\n* Prior therapy: Therapy may not have been received more recently than the timeframes defined below: Craniospinal radiotherapy: At least 3 months have elapsed since prior craniospinal radiotherapy (at doses ≥ 18 Gy). Local radiotherapy: At least 3 months since prior local radiotherapy to primary tumor. Focal radiotherapy: At least 2 weeks since prior focal radiotherapy to symptomatic metastatic sites. Myelosuppressive chemotherapy and\u002For immunotherapy and\u002For biologics: More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas), immunotherapy, or biologics. Hematopoietic growth factor: Seven days must have elapsed since the completion of therapy with colony-stimulating factors (e.g., filgrastim \\[G-CSF\\], sargramostim \\[GM-CSF\\], or erythropoietin), or platelet-stimulating agents.\n* Patients must have recovered from any surgical procedures such as biopsy, with neurological stability for \\> 7 days.\n* Patients must have clear residual disease, defined as tumor that is measurable in two perpendicular diameters on MRI (ie, largest tumor diameter and its largest perpendicular). The size of a measurable lesion at baseline should be at least 2 times the thickness of the slices showing the tumor (adding the interslice gap).\n* Patients must have a Lansky or Karnofsky performance status score of ≥ 50%. Use Karnofsky for patients \\> 16 years of age and Lansky for patients \\\u003C 16 years of age. Patients who are unable to ambulate but who are functional in a wheelchair will be considered ambulatory for the purpose of assessing the performance score.\n* Patients must have normal organ and marrow function.\n* Patient has no evidence of Wolff-Parkinson-White syndrome or high-grade AV block (form of second-degree heart block) on screening ECG.\n* Patient has no evidence of hypertrophic obstructive cardiomyopathy on screening echo.\n* Any patient that reports recent palpitations (within the last month), or concerning findings on echo or ECG must be evaluated and cleared for treatment with digoxin by a cardiologist prior to enrollment. Study PI should be contacted for additional questions\u002Fconcerns regarding these patients.\n* Patients receiving concurrent dexamethasone are eligible, provided dosage is stable or decreasing for ≥7 days prior to study enrollment.\n* Patients must have a stable neurologic status for ≥7 days prior to study enrollment. If a patient experiences neurologic decline following enrollment but prior to day 1 of cycle 1, they should be reassessed for eligibility.\n* Pregnancy: Females of childbearing potential must have a negative urine or serum pregnancy test prior to enrollment. Female patients who are lactating must agree to stop breastfeeding.\n* 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 and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.\n* All patients and\u002For their parents or legal guardians must have the ability to understand and the willingness to sign a written informed consent or assent document.\n\nExclusion Criteria:\n\n* Participants who are receiving concurrent anticancer or any other investigational agents are ineligible.\n* Participants taking digoxin for any reason during treatment for initial diagnosis of medulloblastoma or relapse are ineligible. Exposure to digoxin therapy prior to initial diagnosis of medulloblastoma is allowed.\n* Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to digoxin are ineligible.\n* Patients with serious or inadequately controlled cardiac arrhythmias, including baseline ectopy, ventricular tachycardia, frequent premature ventricular contractions (PVCs), or symptomatic sinus bradycardia are excluded from the study.\n* Patients taking medications that are known to interfere with digoxin metabolism are ineligible.\n* Participants with uncontrolled intercurrent illness, concurrent clinically significant unrelated systemic illness (e.g. serious infection) or significant cardiac, pulmonary, hepatic, or other organ dysfunction that would compromise the patient's ability to tolerate study treatment or would likely interfere with study procedures or results are ineligible.\n* Participants with psychiatric illness\u002Fsocial situations that would limit compliance with study requirements are ineligible.\n* Pregnant women or women unwilling to stop breastfeeding are excluded from this study because it is unknown how pregnant women with recurrent medulloblastoma will metabolize and tolerate digoxin. There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with digoxin in this setting.\n* Participants who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.","30 Years",{"count":272,"type":22},23,[26],"The purpose of this study is to evaluate the efficacy of digoxin in treating relapsed non-SHH, non-WNT medulloblastoma in pediatric and young adult patients.",[30,276],"Medulloblastoma, Non-WNT\u002FNon-SHH",{"date":278,"type":43},"2026-07-07",{"date":280,"type":43},"2026-01-15",{"date":282,"type":22},"2027-02",{"name":284,"class":73},"H. Lee Moffitt Cancer Center and Research Institute",15,{"id":287,"slug":288,"hasResults":12,"nctId":289,"briefTitle":290,"officialTitle":291,"acronym":292,"eligibilityCriteria":293,"healthyVolunteers":12,"sex":17,"minAge":294,"maxAge":4,"enrollmentInfo":295,"targetDuration":4,"studyType":23,"phases":296,"briefSummary":297,"conditions":298,"keywords":316,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":340,"lastUpdatePostDateStruct":341,"startDateStruct":343,"completionDateStruct":345,"leadSponsor":347,"locationsCount":51},"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":7,"type":22},[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)",[299,30,300,301,185,302,303,304,305,306,32,307,308,309,310,311,312,313,92,314,31,315],"Solid Tumor Cancer","High Risk Neuroblastoma","High Grade Gliomas","Paraganglioma","Pheochromocytoma","Neuroendocrine Tumours (NET)","Adrenal Tumours","DIPG","Glioblastoma (GBM)","Osteosarcoma Recurrent","Carcinoma Adrenal","Synovial Sarcomas","Esthesioneuroblastoma","Neuroblastoma Recurrent","Solid Tumor Refractory to Conventional Treatment","Paraganglioma\u002F Phaeochromocytoma","Ependymoma Recurrent",[317,318,319,320,321,322,323,324,325,326,327,328,329,306,330,331,332,333,334,335,336,337,338,31,339],"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":342,"type":43},"2026-06-04",{"date":344,"type":43},"2024-09-20",{"date":346,"type":22},"2029-12",{"name":348,"class":73},"Fundación de investigación HM",{"id":350,"slug":351,"hasResults":12,"nctId":352,"briefTitle":353,"officialTitle":354,"acronym":355,"eligibilityCriteria":356,"healthyVolunteers":12,"sex":17,"minAge":357,"maxAge":116,"enrollmentInfo":358,"targetDuration":4,"studyType":23,"phases":360,"briefSummary":361,"conditions":362,"keywords":4,"overallStatus":161,"whyStopped":4,"lastUpdateSubmitDate":363,"lastUpdatePostDateStruct":364,"startDateStruct":366,"completionDateStruct":367,"leadSponsor":369,"locationsCount":51},"100619556","phase-1-liothyronine-in-combination-with-bit-regimen-for-medulloblastoma-with-or-without-minimal-residual-disease-100619556","NCT07346157","Liothyronine in Combination With BIT Regimen for Medulloblastoma With or Without Minimal Residual Disease","PNOC044: Liothyronine (L-T3) in Combination With Bevacizumab, Irinotecan and Temozolomide (BIT) for Progressive or Relapsed Medulloblastoma (Cohort 1) or as Monotherapy for Medulloblastoma With Minimal Residual Disease (Cohort 2)","PNOC044","Inclusion Criteria:\n\n1. Phase 1 and Phase 2, Cohort 1:\n\n   Participants must have histologically confirmed medulloblastoma that is relapsed\u002Fprogressive following standard upfront therapy. Tissue confirmation of medulloblastoma diagnosis is required at diagnosis and not required at the time of relapse for entry into the study.\n2. Phase 2, Cohort 2: Participants must have cerebrospinal fluid (CSF) with cell-free deoxyribonucleic acid (cf-DNA) + assessed in a Chemiluminescent immunoassay (CLIA)-certified or protocol-approved laboratory. After entry into the study, another CSF sample will be collected and analyzed centrally prior to initiation of protocol therapy to verify cf-DNA positivity.\n3. Evidence of Disease:\n\n   Phase 1 and Phase 2, Cohort 1:\n\n   Participants may have either Measurable or Evaluable Disease Measurable Disease: Participants must have clear residual disease at the time of enrollment, defined as tumor that is measurable in two perpendicular dimensions on MRI Evaluable Disease: Diffuse leptomeningeal disease OR clear MRI evidence of disease that may not be measurable in two perpendicular dimensions.\n\n   Phase 2, Cohort 2:\n\n   For cf-DNA positive cohort: Participants are not required to have measurable or evaluable disease but must have cf-DNA positivity in a CLIA-certified or protocol-approved laboratory, as above.\n4. Prior Therapy: Participants must have received standard upfront therapy for medulloblastoma (either with craniospinal radiation or high dose chemotherapy and autologous stem cell rescue. If other therapy utilized, must be discussed with study chairs prior to participation). Participants for Phase 1 and Phase 2 cohort 1 may have received further chemotherapy and\u002For radiation therapy beyond standard upfront therapy prior to trial enrollment. Participants within the Phase 2 cohort 1 must have experienced at least one, and at most, two relapses prior to study enrollment.\n5. Age 1-25 years old.\n6. Performance Score: Karnofsky ≥ 50 for participants \\> 16 years of age and Lansky ≥ 50 for participants ≤16 years of age (See Appendix A). 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.\n7. For those participants currently treated with levothyroxine (Synthroid) they must have stable dosing for a minimum of 3 months prior to enrollment.\n8. Organ Function Requirements\n\n   1. Peripheral absolute neutrophil count (ANC) ≥ 1000\u002Fcubic millimeters (mm3)\n   2. Platelet count ≥ 75,000\u002Fmicroliter (uL) (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n   3. A serum creatinine \\\u003C 1.5 institutional\u002Freference range upper Limit normal (ULN) based on age and gender\n   4. Total bilirubin ≤ 3 x upper limit of normal (ULN); in presence of Gilbert's syndrome, total bilirubin ≤ 6 x ULN or direct bilirubin ≤ 3 x ULN\n\n      * Alanine aminotransferase (ALT) ≤ 5 x upper limit of normal (ULN)\n      * Aspartate aminotransferase (AST) ≤ 5 x ULN. 3.3.7.4 Adequate Neurologic Function Defined as:\n      * Participants with seizure disorder may be enrolled if well controlled. Participants on non-enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drug. 3.3.7.5 Adequate Cardiac Function Defined as:\n      * Normal left ventricular systolic function on baseline transthoracic echocardiogram (TTE)\n      * Normal left ventricular systolic function is defined as left ventricular ejection fraction (LVEF) \\>55% or shortening fraction (SF) \\>28%.\n\n   AND\n   * No clinically significant arrhythmia on baseline ECG (sinus arrhythmia, sinus tachycardia, sinus bradycardia, early repolarization and 1st degree atrioventricular block when partial response (PR) interval \\\u003C 300 millisecond (ms) are not considered clinically significant arrhythmias).\n   * In addition, the following ECG findings are not considered clinically significant in the setting of a normal echocardiogram:\n   * Left axis deviation\n   * Left atrial enlargement\n   * Right atrial enlargement\n   * Possible left ventricular hypertrophy\n   * Possible right ventricular hypertrophy\n   * Non-specific T wave abnormality 3.3.7.6 For the Phase 1 cohort, normal adrenal axis function is required. For those participants in the Phase 2 cohort, must have controlled adrenal insufficiency \\>3 months (no change in steroid replacement or stress dose plan for at least 3 months).\n   * Normal adrenal axis function as defined as:\n   * Morning (AM) cortisol \\>11mcg\u002Fdeciliter (dL)\n   * If AM cortisol is \\\u003C11 microgram (mcg)\u002FdL, cosyntropin stimulation test with rise to \\>18\n9. Endocrine conditions: Participants with diabetes insipidus, diabetes melitus, or being treated with levothyroxine, must have stable dosing and control for minimum of 3 months prior to enrollment\n10. For Cohort 1 only: participants must have recovered from any surgical procedure before enrolling on this study (see below for examples of major, intermediate, and minor surgical procedures):\n\n    1. Participants with a major surgical procedure within 28 days prior to enrollment should be excluded.\n    2. Participants with an intermediate surgical procedure within 14 days prior to enrollment should be excluded.\n    3. For minor surgical procedures (including Broviac line or infusaport placement), participants should not receive the first planned dose of bevacizumab until the wound is healed and at least 7 days have elapsed.\n    4. There should be no anticipation of need for major surgical procedures during the course of the study.\n11. The effects of L-T3 with chemotherapy on the developing human fetus are unknown. For this reason and because chemotherapy agents as well as other therapeutic agents used in this trial are known to be teratogenic, 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 L-T3 and chemotherapy administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.\n12. Participants must be enroll on PNOC COMP 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. For Cohort 1 only: participants who have previously been treated with BIT in combination. Treatment with individual bevacizumab, irinotecan or TMZ is not an exclusion criteria.\n2. Participants who have had myelosuppressive chemotherapy within 3 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. (Participants receiving chemotherapy directly into the CSF at doses not expected to be myelosuppressive may have received therapy up to 7 days prior to enrollment).\n3. Participants must be at least 7 days since the completion of therapy with a biologic or small molecule agent or non-myelosuppressive chemotherapy 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. Radiation: For participants on the Phase 1 and Phase 2 Cohort 1, the tumor designated as \"measurable\" for protocol purposes must not have received radiation within 6 weeks prior to study entry and focal radiation to areas of symptomatic metastatic disease must not be given within 14 days of study entry. If a new lesion occurs outside the radiation field, the participant is eligible to enroll at any time point from completion of radiation. For Cohort 2 participants, there is no required washout for radiation therapy.\n5. Participants who are receiving any other investigational agents.\n6. History of allergic reactions attributed to compounds of similar chemical or biologic composition to L-T3 or other agents used in study.\n7. Participants receiving any medications or substances that are strong inhibitors or strong inducers of CYP450 enzymes are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated list such as http:\u002F\u002Fmedicine.iupui.edu\u002Fclinpharm\u002Fddis\u002Ftable.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment\u002Finformed consent procedures, the participant and\u002For legal parent or guardian will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering.\n8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection.\n9. Women of childbearing potential must not be pregnant or breast-feeding.\n10. Human immunodeficiency virus- (HIV) positive participants will be ineligible if HIV therapy regimen has not been stable for at least 4 weeks or there is intent to change the regimen within 8 weeks following enrollment, or if they are severely immunocompromised.\n11. Diagnosis of Graves' Disease or other pre-existing hyperthyroid disease.\n12. Participants with severe protein calorie malnutrition that in the opinion of the investigator may not tolerate protocol therapy.\n13. Participants with previous or active clinical cardiovascular disease, including the history of heart failure, myocardial infarction, cardiomyopathy, or ventricular systolic dysfunction on TTE (LVEF \\\u003C55% or SF \\\u003C28%), clinically significant arrhythmia (including atrial fibrillation, atrial flutter, frequent ventricular ectopy), clinically significant peripheral vascular disease.\n14. Participants with uncontrolled systemic hypertension (systolic blood pressure \\> 95th percentile for age and height if participant is ≤ 17 years old)\n15. Participants with uncontrolled diabetes mellitus (HbA1c \\>8%) or uncontrolled diabetes insipidus","1 Year",{"count":359,"type":22},69,[25,26],"This is a Phase 1\u002FPhase 2 study assessing liothyronine (L-T3) immunotherapy and in combination with standard chemotherapy (bevacizumab, irinotecan and temozolomide (BIT)) in children and young adults with medulloblastoma that is relapsed or progressive after standard upfront therapy.",[30,91,92],"2026-05-28",{"date":365,"type":43},"2026-06-01",{"date":128,"type":22},{"date":368,"type":22},"2031-03-31",{"name":370,"class":73},"Sabine Mueller, MD, PhD",{"id":372,"slug":373,"hasResults":12,"nctId":374,"briefTitle":375,"officialTitle":376,"acronym":377,"eligibilityCriteria":378,"healthyVolunteers":12,"sex":17,"minAge":178,"maxAge":18,"enrollmentInfo":379,"targetDuration":4,"studyType":149,"phases":4,"briefSummary":381,"conditions":382,"keywords":4,"overallStatus":161,"whyStopped":4,"lastUpdateSubmitDate":386,"lastUpdatePostDateStruct":387,"startDateStruct":389,"completionDateStruct":391,"leadSponsor":393,"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":380,"type":22},38,"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.",[383,30,384,31,385],"Pediatric Central Nervous System Tumors","Germinoma","Atypical Teratoid\u002FRhabdoid Tumor (AT\u002FRT)","2026-05-10",{"date":388,"type":43},"2026-05-15",{"date":390,"type":22},"2026-04-30",{"date":392,"type":22},"2033-12-31",{"name":394,"class":73},"Ruijin Hospital",{"id":396,"slug":397,"hasResults":12,"nctId":398,"briefTitle":399,"officialTitle":400,"acronym":401,"eligibilityCriteria":402,"healthyVolunteers":12,"sex":17,"minAge":115,"maxAge":18,"enrollmentInfo":403,"targetDuration":4,"studyType":23,"phases":405,"briefSummary":406,"conditions":407,"keywords":4,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":417,"lastUpdatePostDateStruct":418,"startDateStruct":420,"completionDateStruct":422,"leadSponsor":424,"locationsCount":51},"100641039","phase-1-phase-i-study-of-becotatug-vedotin-for-safety-and-efficacy-in-egfr-positive-pediatric-relapsedrefractory-or-metastatic-solid-tumors-100641039","NCT07584499","Phase I Study of Becotatug Vedotin for Safety and Efficacy in EGFR-Positive Pediatric Relapsed\u002FRefractory or Metastatic Solid Tumors","A Phase I Clinical Study to Explore the Safety and Efficacy of Becotatug Vedotin in Pediatric Patients With EGFR-Positive Relapsed\u002FRefractory or Metastatic Solid Tumors","MRG003","Inclusion Criteria:\n\n* All participants must meet all of the following criteria to be eligible for enrollment:\n\nInformed Consent: The patient (and\u002For legal guardian, as age-appropriate) fully understands the study, voluntarily agrees to participate, and signs a written informed consent form (ICF). A separate biomarker consent form is required for EGFR testing prior to screening.\n\nAge: 2 to 18 years old at the time of consent. Life Expectancy: Estimated overall survival of at least 3 months.\n\nHistologically Confirmed Disease: Pathologically confirmed relapsed\u002Frefractory or metastatic EGFR-positive solid tumor, belonging to one of the following subtypes:\n\nHead and neck squamous cell carcinoma, nasopharyngeal carcinoma, or lymphoepithelial carcinoma that progressed during or after at least one line of platinum-based chemotherapy and PD-1\u002FPD-L1 inhibitor therapy Rhabdomyosarcoma Neuroblastoma Medulloblastoma Wilms tumor Atypical teratoid\u002Frhabdoid tumors (AT\u002FRTs) Diffuse intrinsic pontine gliomas (DIPGs) Other EGFR-positive solid tumor subtypes deemed eligible by the investigator Measurable Disease: At least one measurable tumor lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST v1.1 criteria (longest diameter ≥10 mm; pathological lymph node short axis ≥15 mm).\n\nPerformance Status: Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.\n\nAdequate Bone Marrow Function:\n\nAbsolute neutrophil count (ANC) ≥1.5 × 10⁹\u002FL Platelet count ≥75 × 10⁹\u002FL Hemoglobin ≥80 g\u002FL Exception for patients with bone marrow involvement: ANC ≥1.0 × 10⁹\u002FL, platelets ≥50 × 10⁹\u002FL, hemoglobin ≥75 g\u002FL\n\nAdequate Hepatic and Renal Function:\n\nSerum creatinine ≤1.5 × upper limit of normal (ULN) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN Total bilirubin ≤1.5 × ULN Exception for patients with liver involvement: AST\u002FALT ≤5 × ULN, total bilirubin ≤3 × ULN\n\nExclusion Criteria:\n\n* Participants will be excluded from the study if they meet any of the following criteria:\n\nHypersensitivity: Known hypersensitivity to any component of Becotatug Vedotin (MRG003) or its excipients.\n\nSymptomatic CNS Metastases: Presence of symptomatic central nervous system (CNS) metastases.\n\nPrior Malignancies: History of other primary malignant tumors, except for:\n\nLocally excised basal cell or squamous cell carcinoma of the skin Cervical carcinoma in situ Any prior malignancy that has been in complete remission for ≥3 years without treatment Note: Melanoma (any stage) is explicitly excluded\n\nSignificant Liver Disease: Clinically significant liver disease, including:\n\nPositive hepatitis C virus (HCV) antibody Chronic active hepatitis B (HBV DNA \\>20,000 IU\u002FmL) HIV Infection: Known human immunodeficiency virus (HIV) infection. Severe Ocular Abnormalities: History of severe ophthalmologic conditions, such as severe dry eye syndrome or exposure keratitis.\n\nUncontrolled Systemic Diseases: Severe or uncontrolled medical conditions, including:\n\nInterstitial lung disease or pneumonitis Active autoimmune diseases requiring systemic immunosuppressive therapy\n\nCardiac Disease: Clinically significant cardiac dysfunction or cardiac disease, including:\n\nCongestive heart failure (New York Heart Association Class ≥II) Uncontrolled arrhythmias QTc interval prolongation \\>450 ms (males) or \\>470 ms (females) Recent Antitumor Therapy: Received any systemic antitumor therapy (chemotherapy, biological therapy, immunotherapy, targeted therapy) within 3 weeks prior to the first dose of study drug, and have not recovered to CTCAE v4.03 Grade ≤1 (except alopecia).\n\nRecent Major Surgery: Underwent major surgical procedure within 3 weeks prior to the first dose of study drug.\n\nPlanned Surgery: Planned surgical procedure during the study period, or any surgery deemed necessary by the investigator.\n\nPrior EGFR Therapy Toxicity: History of severe skin toxicity caused by prior EGFR-targeted therapy, or chronic skin disease requiring ongoing oral or intravenous treatment.\n\nOther Significant Risks: Any other concurrent medical condition that, in the investigator's judgment, would increase the risk of toxicity or compromise the patient's ability to complete the study.",{"count":404,"type":22},51,[25],"There is a significant unmet medical need for effective therapies for pediatric relapsed\u002Frefractory solid tumors. EGFR is highly and stably expressed in multiple pediatric solid tumor subtypes, and adult Phase I data of Becotatug Vedotin demonstrated a manageable safety profile and promising antitumor activity in EGFR-positive advanced solid tumors.This is a multicenter, non-randomized, single-arm, open-label Phase I clinical trial sponsored by Sun Yat-sen University Cancer Center (SYSUCC). The trial evaluates the safety, tolerability, pharmacokinetics (PK), immunogenicity, and preliminary efficacy of Becotatug Vedotin-an EGFR-targeted antibody-drug conjugate (ADC)-in pediatric patients with EGFR-positive relapsed\u002Frefractory or metastatic solid tumors.",[408,409,410,411,412,30,413,414,415,416],"Head and Neck Squamous Cell Carcinoma (HNSCC) - Recurrent\u002FMetastatic (R\u002FM)","Nasopharyngeal Carcinoma","Lymphoepithelial Carcinoma","Rhabdomyosarcoma","Neuroblastoma","Wilms Tumor","Atypical Teratoid\u002FRhabdoid Tumors","Diffuse Intrinsic Pontine Gliomas","Other EGFR-positive Pediatric Solid Tumors Deemed Eligible by the Investigator","2026-05-07",{"date":419,"type":43},"2026-05-13",{"date":421,"type":22},"2026-05-30",{"date":423,"type":22},"2028-05-30",{"name":425,"class":73},"Sun Yat-sen University",{"id":427,"slug":428,"hasResults":12,"nctId":429,"briefTitle":430,"officialTitle":430,"acronym":431,"eligibilityCriteria":432,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":433,"targetDuration":4,"studyType":23,"phases":435,"briefSummary":436,"conditions":437,"keywords":441,"overallStatus":161,"whyStopped":4,"lastUpdateSubmitDate":447,"lastUpdatePostDateStruct":448,"startDateStruct":450,"completionDateStruct":451,"leadSponsor":453,"locationsCount":455},"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":434,"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.",[438,32,29,31,30,185,439,440],"Brain (Nervous System) Cancers","Rare Primary Brain Tumors","Rare CNS Primary Tumors",[442,443,444,445,446],"pharmacoscopy","drug testing","refractory tumor","drug repurposing","personalized medicine","2026-04-29",{"date":449,"type":43},"2026-05-06",{"date":365,"type":22},{"date":452,"type":22},"2028-09-15",{"name":454,"class":73},"University of Zurich",3,{"id":457,"slug":458,"hasResults":12,"nctId":459,"briefTitle":460,"officialTitle":460,"acronym":4,"eligibilityCriteria":461,"healthyVolunteers":12,"sex":17,"minAge":462,"maxAge":463,"enrollmentInfo":464,"targetDuration":4,"studyType":23,"phases":466,"briefSummary":467,"conditions":468,"keywords":475,"overallStatus":161,"whyStopped":4,"lastUpdateSubmitDate":481,"lastUpdatePostDateStruct":482,"startDateStruct":484,"completionDateStruct":486,"leadSponsor":488,"locationsCount":51},"100632643","mynavigate-a-guide-to-after-treatment-effects-for-adolescents-and-young-adults-100632643","NCT07516353","my.naviGATE: A Guide to After-Treatment Effects for Adolescents and Young Adults","Inclusion Criteria:\n\n* Patients aged 15-24 who are currently undergoing cancer treatment at one of the three participating sites: DFCI, CNH, or RPOCH.\n* Patients must have initiated and be actively receiving cancer directed therapy for a newly diagnosed cancer.\n* Patients must be actively receiving cancer directed therapy, between the time of diagnosis and end of therapy for the following diagnoses: 1) Sarcomas: including osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma; 2) Acute Myeloid Leukemia (AML); 3) Acute Lymphoblastic Leukemia\u002FLymphoma (ALL); 4) Hodgkin and mature B-cell Lymphomas; and 5) Medulloblastoma.\n* Patients whose treatment includes alkylators, anthracyclines, and\u002For radiation.\n\nInclusion of Children:\n\n• This study is designed to keep AYAs aged 15-24 engaged in cancer survivorship care and therefore a subset of participants will be \\\u003C18 years of age. The rationale for inclusion of children in this study is that AYA cancer survivors are particularly vulnerable to loss to follow-up and consequently lack of risk-based survivorship care, resulting in increased risk for preventable toxicity. Many existing interventions to improve engagement in survivorship screening and care are introduced after treatment completion and in long-term survivorship. Yet, for patients who are unaware of their late effect risks, and\u002For those who move frequently and are lost to follow-up, this may be too late. This study is designed to improve awareness of and engagement in risk-informed survivorship care for AYAs. This study presents no more than minimal risk to participants.\n\nExclusion Criteria:\n\n* Patients who are unwilling to give informed consent or assent to participate will be excluded. For patients under 18, patients whose guardians do not give informed consent will be excluded.\n* Patients with no chance of cure as identified by the AYA's physician, will be excluded given that issues of survivorship are not relevant and may be distressing to this population. Similarly, patients with relapsed or refractory disease will also be excluded.\n* Patients who are non-English-speaking and -reading will be excluded as the digital tool is being developed initially in English.\n* We will seek physician permission before offering enrollment to patients. If the provider team requests that the patient not be approached to participate, the patient will be excluded.","15 Years","24 Years",{"count":465,"type":22},143,[88],"This study aims to design and test a novel, personalized digital intervention-my.naviGATE-for adolescent and young adults (AYA) with cancer. my.naviGATE is a mobile app that provides personalized survivorship education, access to virtual peer navigation, and responsive participant-reported outcomes (PROs).",[469,470,471,411,472,473,17,30,474],"Sarcoma","Osteosarcoma","Ewing Sarcoma","Acute Myeloid Leukemia","Aml","Acute Lymphoblastic Leukemia ,Lymphomas",[476,477,478,479,480,469,470,471,411,472,473,17,30],"Cancer Survivorship","Adolescent and Young Adult Cancer","Late Effects of Cancer Treatment","Hodgkin and mature B-cell Lymphomas","Acute Lymphoblastic Leukemia\u002FLymphoma","2026-03-31",{"date":483,"type":43},"2026-04-08",{"date":485,"type":22},"2026-08-20",{"date":487,"type":22},"2030-12-31",{"name":489,"class":73},"Dana-Farber Cancer Institute",{"id":491,"slug":492,"hasResults":12,"nctId":493,"briefTitle":494,"officialTitle":494,"acronym":4,"eligibilityCriteria":495,"healthyVolunteers":12,"sex":17,"minAge":145,"maxAge":270,"enrollmentInfo":4,"targetDuration":4,"studyType":496,"phases":4,"briefSummary":497,"conditions":498,"keywords":4,"overallStatus":503,"whyStopped":4,"lastUpdateSubmitDate":504,"lastUpdatePostDateStruct":505,"startDateStruct":4,"completionDateStruct":4,"leadSponsor":507,"locationsCount":51},"100330361","an-intermediate-expanded-use-trial-of-dfmo-100330361","NCT03581240","An Intermediate Expanded Use Trial of DFMO","Inclusion Criteria:\n\n* Age: 0-30 years at the time of initial diagnosis.\n* Diagnosis: Histologic verification at either the time of original diagnosis or a previous relapse of High Risk neuroblastoma, medulloblastoma, atypical teratoid rhabdoid tumor, embryonal tumor with abundant neuropil and true rosettes, ependymoblastoma, medulloepithelioma and other rare pediatric MYC, ODC or LIN28\u002FLet7 driven tumors (each type will form a new subset).\n* Disease Status: Subjects must be in one of the following disease categories:\n\n  1. High risk neuroblastoma patients that have completed standard of care upfront therapy and are not eligible for NMTRC014.\n  2. Medulloblastoma patients who have completed standard of care therapies.\n  3. Relapsed\u002Frefractory neuroblastoma patients who have completed standard of care therapies.\n  4. Rare tumors with increased LIN28 expression or MYCN amplification or up regulation of ornithine decarboxylase who have completed standard of care therapies.\n* Subjects are not eligible to enroll on DFMO studies NMTRC002, NMTRC003, NMTRC010, or NMTRC014.\n* A negative serum or urine pregnancy test is required for female subjects of child bearing potential (onset of menses or ≥13 years of age).\n* Both male and female post-pubertal study subjects need to agree to use one of the more effective birth control methods during treatment and for six months after treatment is stopped. These methods include total abstinence (no sex), oral contraceptives (\"the pill\"), an intrauterine device (IUD), levonorgestrol implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam with a condom is recommended.\n* Informed Consent: All subjects and\u002For legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines\n\nExclusion Criteria:\n\n* BSA (m2) of \\\u003C0.25\n* Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.","EXPANDED_ACCESS","To provide DFMO in an expanded use setting to subjects with relapsed rare tumors with increased LIN28 expression or MYCN amplification or up regulation of ornithine decarboxylase.",[412,30,499,500,501,502],"Typical Teratoid Rhabdoid Tumor","Embryonal Tumor With Abundant Neuropil and True Rosettes","Ependymoblastoma","Medulloepithelioma","AVAILABLE","2026-02-18",{"date":506,"type":43},"2026-02-20",{"name":72,"class":73},{"id":509,"slug":510,"hasResults":12,"nctId":511,"briefTitle":512,"officialTitle":513,"acronym":4,"eligibilityCriteria":514,"healthyVolunteers":12,"sex":17,"minAge":4,"maxAge":515,"enrollmentInfo":516,"targetDuration":4,"studyType":23,"phases":518,"briefSummary":519,"conditions":520,"keywords":521,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":540,"lastUpdatePostDateStruct":541,"startDateStruct":543,"completionDateStruct":545,"leadSponsor":547,"locationsCount":548},"100480375","phase-2-molecular-and-clinical-risk-directed-therapy-for-infants-and-young-children-with-newly-diagnosed-medulloblastoma-100480375","NCT05535166","Molecular and Clinical Risk-Directed Therapy for Infants and Young Children With Newly Diagnosed Medulloblastoma","SJiMB21: Phase 2 Study of Molecular and Clinical Risk-Directed Therapy for Infants and Young Children With Newly Diagnosed Medulloblastoma","Inclusion Criteria - Screening Phase (All Patients)\n\n* Participants with presumptive\u002Fsuspected newly diagnosed medulloblastoma.\n* Participant meets one of the following criteria at the time of screening:\n\n  * Age \\\u003C 36 months OR Age ≥ 36 months and \\\u003C 60 months with presumptive\u002Fsuspected non-metastatic disease\n* Participant must have adequate tumor tissue from primary tumor for central review of pathology and molecular classification by methylation and IHC\n* Participant must be able to begin treatment as outlined in the protocol within 36 days of definitive surgery (day of surgery is Day 0). In case a second surgery is clinically indicated to remove the residual tumor prior to starting treatment, the second surgery will be considered as the definitive surgery (Day 0).\n* Parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines.\n\nExclusion Criteria - Screening Phase\n\n* Participants with other clinically significant medical disorders (i.e., 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 the study procedure.\n\nInclusion Criteria - Study Enrollment (All Patients)\n\n* Participant must be \\\u003C 60 months of age at time of enrollment.\n\n  * Note: Each treatment stratum has additional specific age requirements\n* Participant must have confirmation of newly diagnosed medulloblastoma per Central Review:\n\n  * Central review includes histopathology, IHC and St. Jude Clinical Genomic Methylation Profiling conducted on MLPNet. If tissue or the extracted DNA does not meet quality control criteria for methylation analysis or if methylation classifier is unable assign molecular group\u002Fsubgroup within the assigned classifier (MLPNet) parameters, then IHC will be used to define molecular group of these cases. IHC cannot be used to determine molecular subgroup. Therefore, IHC defined SHH patients will be enrolled on Stratum S-1 under \"SHH-NOS\", and all NWNS and indeterminate molecular group will be enrolled on stratum N.\n  * Note: Diagnosis of medulloblastoma, as well as group and subgroup assignment, will be done by central pathology review at St. Jude only. No outside testing is allowed for trial enrollment.\n* Participant must have disease staged by MRI of the brain and spine and by cytologic examination of CSF\\* and be placed into the following categories:\n\n  * M0: no evidence of metastatic disease.\n\n    * must include a negative CSF cytology result\n  * M1: Tumor cells found in the CSF but no other evidence of metastasis\n  * M2: Intracranial tumor beyond the primary tumor site\n  * M3: Metastatic disease in the spine\n  * M4: Extraneural metastatic disease\n  * \\*All participants are to undergo CSF cytologic examination regardless of presence or absence of gross metastatic disease unless procedure is medically contraindicated. CSF is to be obtained by lumbar puncture (LP) performed at least 10 days after surgery. If LP is medically contraindicated, ventricular CSF from a shunt or Ommaya reservoir may be used for staging but this is not the preferred option due to lower sensitivity. If LP is medically contraindicated and the patient doesn't have a shunt or reservoir for CSF sampling, the treating physician should reach out to PI or Co-PI regarding decision on enrollment to SJiMB21. The decision to enroll without CSF cytology will be made on case-by-case basis.\n  * Note: Participants who have M2 disease and positive CSF will be assigned to M3.\n  * Note: Participants will be assigned to the highest stage number for which they meet eligibility.\n  * Note: Treatment stratums may have additional stage requirements.\n* Patient must have received no previous radiotherapy, chemotherapy, or other brain tumor-directed therapy other than corticosteroid therapy and surgery.\n* Participant must have a Lansky performance score of \\> 30 (except for patients with posterior fossa syndrome.\n* Participant must have adequate organ function prior to study entry, as defined by:\n\n  * Absolute neutrophil counts (ANC) \\>750\u002Fmm\\^3\n  * Platelet count ≥ 50,000\u002Fmm\\^3 without support of a platelet transfusion within 7 days\n  * Hemoglobin ≥8.0 g\u002FdL (with or without support of a blood transfusion).\n  * Normal liver function as defined by Alanine aminotransferase (ALT) concentration ≤ 3 x 45 U\u002FL and total bilirubin ≤ 3 x 1.0.\n* Adequate renal function as defined by a serum creatinine concentration:\n\n  * Age - 0 to \\\u003C1year; Maximum Serum Creatinine (mg\u002Fdl) - Male 0.5; Female 0.5\n  * Age - 1 to \\\u003C 2years; Maximum Serum Creatinine (mg\u002Fdl) - Male 0.6; Female 0.6\n  * Age - 1 to \\\u003C 2yearsr; Maximum Serum Creatinine (mg\u002Fdl) - Male 0.8; Female 0.8\n* Participant's parent or legal guardian has the ability to understand and the willingness to sign a written informed consent document according to institutional guidelines.\n\nInclusion Criteria - Stratum S-2\n\n* Participant must have confirmed diagnosis of the following medulloblastoma molecular group and subgroup per Central Review.\n\n  * Medulloblastoma SHH-2\n* Participant must meet one of the following criteria at time of enrollment:\n\n  * Age \\\u003C36 months OR Age ≥ 36 months and \\\u003C 60 months with non-metastatic disease (M0) Inclusion Criteria - Stratum S-1\n* Participant must have confirmed diagnosis of one of the following medulloblastoma molecular subgroups per Central Review.\n\n  * Medulloblastoma SHH-1\n  * Medulloblastoma SHH-3\n  * Medulloblastoma SHH-4\n  * Medulloblastoma SHH-NOS\n\n    * Includes medulloblastoma cases that could not be assigned to a molecular subgroup using the DNA methylation classifier, but which are in the SHH group and\u002For cases defined as SHH by IHC.\n* Participant must be \\\u003C 36 months of age at time of enrollment\n\n  * Note: Patients who are \\\u003C 36 months of age, regardless of metastatic status (M0\u002FM+), are eligible for enrollment on stratum S-1.\n\nInclusion Criteria - Stratum N\n\n* Participant must have confirmed diagnosis of one of the following medulloblastoma molecular subgroups per Central Review.\n\n  * Medulloblastoma G3\n  * Medulloblastoma G4\n  * Medulloblastoma - Not classified into SHH (i.e., NWNS or indeterminate)\n\n    * Includes medulloblastoma cases that could not be assigned to a molecular group using the DNA methylation classifier but which are in the NWNS class and\u002For defined as NWNS by IHC.\n* Participant must be \\\u003C36 months of age at time of enrollment\n* All NWNS patients (M+ and M0) are eligible for enrollment in stratum N\n\nExclusion Criteria - All Patients\n\n* CNS embryonal tumor other than medulloblastoma, for example, patients with diagnosis of Atypical Teratoid\u002FRhabdoid Tumor (ATRT), PNET, Pineoblastoma, Ependymoma, and ETMR are excluded.\n* Participant with prior treatment for medulloblastoma, including:\n\n  * Radiotherapy\n  * Chemotherapy\n  * Cancer directed immunotherapy\n  * Targeted agents\n  * NOTE: Corticosteroid therapy is acceptable; prior treatment with chemotherapy, immunotherapy or targeted agents for non-cancer directed indications are acceptable as long as these have been stopped at least 14 days prior to start of therapy or 2 half-lives from last dose. (i.e., methotrexate for juvenile rheumatoid arthritis, JAK inhibitor therapy for eczema, etc.)\n* Participant who is actively receiving any other investigational agents.\n* Participant with other clinically significant medical disorders (i.e., 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 the study procedures or results.","59 Months",{"count":517,"type":22},130,[26],"This is a multi-center, multinational phase 2 trial that aims to explore the use of molecular and clinical risk-directed therapy in treatment of children 0-4.99 years of age with newly diagnosed medulloblastoma.",[30],[522,523,524,525,526,527,528,529,530,531,532,533,534,535,536,537,538,539],"SJiMB21","Brain Cancer","Brain Tumors in Children","Medulloblastoma Sonic Hedgehog subgroup 1","Medulloblastoma Sonic Hedgehog subgroup 2","Medulloblastoma Sonic Hedgehog subgroup 3","Medulloblastoma Sonic Hedgehog subgroup 4","Medulloblastoma Sonic Hedgehog-not otherwise specified","Medulloblastoma G3","Medulloblastoma G4","Medulloblastoma indeterminate","MLPNet","Neural Net Classification Pipeline","Non-WNT non-SHH medulloblastoma","Posterior fossa syndrome","St. Jude Brain Tumor Studies","Treatment for Brain Tumors in Infants and Young Children","Untreated Childhood Medulloblastoma","2026-02-10",{"date":542,"type":43},"2026-02-12",{"date":544,"type":43},"2022-12-20",{"date":546,"type":22},"2035-07",{"name":262,"class":73},10,{"id":550,"slug":551,"hasResults":12,"nctId":552,"briefTitle":553,"officialTitle":554,"acronym":4,"eligibilityCriteria":555,"healthyVolunteers":12,"sex":17,"minAge":115,"maxAge":59,"enrollmentInfo":556,"targetDuration":4,"studyType":23,"phases":558,"briefSummary":559,"conditions":560,"keywords":571,"overallStatus":161,"whyStopped":4,"lastUpdateSubmitDate":575,"lastUpdatePostDateStruct":576,"startDateStruct":578,"completionDateStruct":580,"leadSponsor":582,"locationsCount":137},"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.",{"count":557,"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)",[561,562,563,564,565,30,91,566,92,31,567,568,569,570],"Central Nervous System Neoplasms","Brain Tumor","Brain Tumor, Recurrent","Brain Tumor, Pediatric","Brain Tumor Adult","Medulloblastoma, Adult","Atypical Teratoid\u002FRhabdoid Tumor","Embryonal Tumor With Multilayered Rosettes","Pineoblastoma","Leptomeningeal Disease",[561,562,564,572,573,30,91,566,92,31,567,574,569,570],"Brain Tumor, Adult","Brain Tumor Recurrent","Embryonal Tumor with Multilayered Rosettes","2026-01-28",{"date":577,"type":43},"2026-02-05",{"date":579,"type":22},"2026-07",{"date":581,"type":22},"2032-08-31",{"name":583,"class":73},"Robbie Majzner",{"id":585,"slug":586,"hasResults":12,"nctId":587,"briefTitle":588,"officialTitle":589,"acronym":4,"eligibilityCriteria":590,"healthyVolunteers":12,"sex":17,"minAge":357,"maxAge":270,"enrollmentInfo":591,"targetDuration":4,"studyType":23,"phases":592,"briefSummary":593,"conditions":594,"keywords":601,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":611,"lastUpdatePostDateStruct":612,"startDateStruct":614,"completionDateStruct":616,"leadSponsor":618,"locationsCount":51},"100599631","phase-1-gpc2-car-t-cell-therapy-for-relapsed-or-refractory-medulloblastoma-in-children-and-young-adults-100599631","NCT07087002","GPC2-CAR T Cell Therapy for Relapsed or Refractory Medulloblastoma in Children and Young Adults","Phase I Clinical Trial of GPC2 Chimeric Antigen Receptor T (GPC2-CAR T) Cells for Relapsed or Refractory Medulloblastoma in Children and Young Adults","Inclusion Criteria:\n\n1. Diagnosis: Histologically confirmed diagnosis of medulloblastoma or other primary CNS embryonal tumor according to 2021 CNS WHO Classification (5th edition)\n\n   * Other acceptable CNS embryonal tumors include:\n   * Embryonal Tumor with Multilayered Rosettes (ETMR)\n   * Pineoblastoma\n   * Atypical Teratoid\u002FRhabdoid Tumor (ATRT) of the CNS\n   * CNS neuroblastoma, FOXR2-activated\n   * CNS Embryonal Tumor NOS\n2. Recurrent\u002FRefractory Disease: History of relapsed and\u002For recurrent disease defined as tumor progression or recurrence following initial diagnosis and upfront treatment with curative intent, or failure to achieve disease control with standard curative-intent therapy.\n3. GPC2 Positive: H-score ≥ 100 by IHC staining performed on the (Prescreening Protocol IRB-78780, PI: Katherine Ryan, DO) at Stanford Clinical Anatomic Pathology Lab for GPC2 from a tumor sample any time since initial diagnosis.\n4. Evaluable Disease: Evaluable disease as per radiographic findings and\u002For positive cerebrospinal fluid cytology within 28 days of enrollment.\n5. Patients with VP shunts: Patients with pre-existing ventriculo-peritoneal (VP) shunt devices must have a programmable shunt device to enroll on this study. A VP shunt is not a requirement for this study.\n6. Prior therapy: No limit to the number of prior treatment regimens. Toxicities due to prior therapy must be stable or recovered to ≤ Grade 1 (except for clinically non-significant toxicities such as alopecia, nutritional support measures, electrolyte abnormalities, or those not impacting the investigator's ability to assess treatment emergent toxicities).\n\n   At time of enrollment, subjects are on track to meet the required therapy wash out period(s) prior to apheresis.\n\n   a. At least 6 weeks following craniospinal radiation therapy. i. At least 14 days wash-out needed following small volume radiotherapy (i.e., Stereotactic Radiosurgery (SRS)).\n\n   b. At least 21 days or 5 half-lives (whichever is shorter) must have elapsed since any prior systemic therapy, except for systemic inhibitory\u002Fstimulatory immune checkpoint therapy, which requires 5 half-lives.\n\n   c. At least 28 days following bevacizumab treatment. d. At least 30 days following any investigational drug. e. At least 12 weeks following systemic inhibitory or stimulatory immune checkpoint therapy.\n7. Age: ≥ 12 months to ≤ 30 years of age at time of enrollment The first 3 subjects treated with GPC2-CAR T cells must be ≥ 3 years old at time of infusion\n8. Performance Status: Subjects ≥ 16 years of age must have Karnofsky ≥ 60%. Subjects \\\u003C 16 years of age must have Lansky scale 60%; or ECOG performance status ≤ 2 (see Section 11.3).\n9. Normal Organ and Marrow Function \\[supportive care is allowed per institutional standards, i.e., filgrastim, transfusion\\]\n\n   1. Hemoglobin ≥ 8 g\u002FdL\n   2. Absolute Neutrophil Count (ANC) ≥ 1,000\u002FμL\n   3. Platelet count ≥ 75,000\u002FμL, with no platelet transfusion within 96 hours prior to enrollment\n   4. Absolute lymphocyte count (ALC) ≥ 150\u002FμL\n   5. PT\u002FINR, PTT ≤ 1.5 x ULN for age\n\n      Adequate renal, hepatic, cardiac, and pulmonary function defined as:\n   6. Serum creatinine \\\u003C 1.5 x ULN for age and gender, OR creatinine clearance or GFR (radioisotope or iothalamate) ≥ 70 mL\u002Fmin\u002F1.73 m2\n   7. Serum ALT or AST ≤ 3x ULN\n   8. Total bilirubin ≤ 1.5 mg\u002FdL, unless subject has Gilbert's Syndrome\n   9. Cardiac ejection fraction ≥ 45%\n   10. No evidence of physiologically significant pericardial effusion as determined by an ECHO\n   11. No clinically significant ECG findings\n   12. No clinically significant pleural effusion\n   13. Pulse oximetry ≥ 92% on room air, OR forced vital capacity ≥ 50% of predicted value\n10. Not Pregnant: Females of childbearing potential must have a negative pregnancy test.\n11. Contraception: Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four (4) months after receiving the preparative regimen or for as long as CAR T cells are detectable in peripheral blood.\n12. Must provide informed consent. All subjects ≥ 18 years of age must be able to give informed consent. For subjects \\\u003C18 years old or adults with limited decision-making capacity, their legal authorized representative (LAR) (i.e., parent or guardian) must give informed consent. Pediatric subjects will be included in age-appropriate discussion and assent will be obtained for those \\> 7 years of age, when appropriate. If a minor becomes of age during participation of this study, he\u002Fshe will be asked to reconsent as an adult.\n\nExclusion Criteria\n\n1. Any patient with metastatic disease OUTSIDE the CNS.\n2. Unwilling or unable, in the investigator's judgement, to have a CSF reservoir (Ommaya or Rickham) placed. Does not apply to subjects who have a pre-existing device suitable for ICV delivery of CAR T cells and ICP monitoring.\n3. Clinical evidence of active\u002Fon-going significant increased intracranial pressure (i.e., impending herniation) or uncontrolled seizures.\n4. Prior receipt of a chimeric antigen receptor (CAR)-based therapy.\n5. Currently receiving anticoagulation therapy.\n6. Known history of infection with HIV or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive).\n\n   EXCEPTION: A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and\u002For nucleic acid testing.\n7. Pregnancy or breastfeeding in a postpartum female.\n8. Known sensitivity or allergy to any agents\u002Freagents used in this study.\n9. History of prior other malignancy. EXCEPTION: Previously diagnosed and definitively treated more than 5 years prior to enrollment or whose prognosis is deemed good enough to not warrant surveillance.\n10. Primary immunodeficiency or history of autoimmune disease (e.g., Crohn's, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression\u002Fsystemic disease modifying agents within the last 2 years.\n11. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment.\n12. Significant medical diseases or poorly controlled conditions that, in the judgement of the investigator, put the subject at an unacceptable risk of complications, including but not limited to: uncontrolled diabetes mellitus, chronic obstructive pulmonary disease, pulmonary fibrosis, clinically significant inflammatory disorders, immunodeficiency (e.g., HIV infection), immunocompromised for reasons other than malignancy (e.g., chronic corticosteroid therapy or other immunosuppressive therapy), renal failure including patients requiring dialysis, or clinically significant liver dysfunction.\n13. In the Investigator's judgment, the subject or parents\u002Fcaregivers (as required) will not be able to comply with the study procedures outlined in the study protocol including follow-up visits.",{"count":118,"type":22},[25],"This is a single-site, open-label Phase 1 clinical trial evaluating the feasibility, safety, and preliminary activity of autologous GPC2-targeted chimeric antigen receptor (CAR) T cells administered via intracerebroventricular (ICV) infusion in children and young adults with relapsed or refractory medulloblastoma or other eligible Central Nervous System (CNS) embryonal tumors.",[30,595,194,190,596,597,569,598,599,600],"Central Nervous System Embryonal Tumor","Pediatric Brain Tumor","Embryonal Tumor With Multilayered Rosettes (ETMR)","Atypical Teratoid\u002FRhabdoid Tumor (ATRT) of the CNS","CNS Neuroblastoma","FOXR2-activated",[602,603,604,605,606,30,607,608,609,569,598,610,600],"GPC2-CAR T cells","Chimeric Antigen Receptor T cells","Intracerebroventricular CAR T","Pediatric CNS tumors","Immunotherapy","Refractory brain tumors","T cell therapy","Embryonal Tumor with Multilayered Rosettes (ETMR)","CNS neuroblastoma","2026-01-26",{"date":613,"type":43},"2026-01-27",{"date":615,"type":43},"2025-08-28",{"date":617,"type":22},"2027-08",{"name":619,"class":73},"Stanford University",{"id":621,"slug":622,"hasResults":12,"nctId":623,"briefTitle":624,"officialTitle":625,"acronym":4,"eligibilityCriteria":626,"healthyVolunteers":12,"sex":17,"minAge":294,"maxAge":116,"enrollmentInfo":627,"targetDuration":4,"studyType":23,"phases":629,"briefSummary":630,"conditions":631,"keywords":633,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":655,"lastUpdatePostDateStruct":656,"startDateStruct":658,"completionDateStruct":660,"leadSponsor":662,"locationsCount":51},"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":628,"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.",[31,30,32,632],"Primary Brain Tumor",[634,635,636,637,638,639,640,641,642,643,644,645,646,647,648,649,650,651,652,653,654],"IDO","indoleamine 2,3-dioxygenase","indoximod","BTK","Bruton's Tyrosine Kinase","ibrutinib","immunotherapy","pediatric","childhood","brain tumor","brain cancer","glioblastoma","medulloblastoma","ependymoma","PNET","cyclophosphamide","etoposide","immune","central nervous system","CNS","temozolomide","2026-01-07",{"date":657,"type":43},"2026-01-09",{"date":659,"type":43},"2022-02-08",{"date":661,"type":22},"2028-09-30",{"name":663,"class":73},"Theodore S. Johnson",{"id":665,"slug":666,"hasResults":12,"nctId":667,"briefTitle":668,"officialTitle":668,"acronym":4,"eligibilityCriteria":669,"healthyVolunteers":12,"sex":17,"minAge":4,"maxAge":670,"enrollmentInfo":671,"targetDuration":4,"studyType":23,"phases":673,"briefSummary":675,"conditions":676,"keywords":4,"overallStatus":161,"whyStopped":4,"lastUpdateSubmitDate":677,"lastUpdatePostDateStruct":678,"startDateStruct":680,"completionDateStruct":682,"leadSponsor":684,"locationsCount":137},"100615322","phase-3-comparison-of-neurocognitive-outcome-in-two-standard-regimen-for-treatment-of-low-risk-medulloblastoma-100615322","NCT07291102","Comparison of Neurocognitive Outcome in Two Standard Regimen for Treatment of Low-risk Medulloblastoma","Inclusion Criteria for screening:\n\n* Age at diagnosis \\\u003C 5 years\n* Patients with institutional suspicion or diagnosis of SHH-activated MB\n* Patient and family in social circumstances that will allow neuropsychological follow-up\n* Ability of parents\u002Flegal representatives to understand the patient information and to personally sign and date the informed consent to participate in screening procedures\n* Patient and the parents\u002Flegal representative are able and willing to participate in the entire study (if patient is eligible)\n\nExclusion Criteria for overall study:\n\n* Patients previously treated for any other brain tumor or any type of malignant disease\n* Patients, in whom compliance with toxicity management guidelines and study procedures cannot be assured\n* History of hypersensitivity to an investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of an investigational medicinal product.\n* Patients\u002Fparents who do not wish to abstain from treatment with live vaccines during study participation\n* Patients with a language barrier too extensive to complete neuropsychological tests based on the investigator's judgement\n* Patients with severe premorbid developmental delay (based on the investigator's judgement), which will not allow WPPSI-IV assessment after 2.5 years\n* Patients cannot undergo MRI\n\nInclusion Criteria for Bridging chemotherapy (carboplatin\u002Fetopiside) in interventional arms:\n\n* Patients with SHH-activated MB, TP53-wt demonstrated by IHC for Gab1 or p75-NGFR, Yap1, beta-catenin, and TP53 (lack of strong and widespread nuclear p53 positivity) on central review according to WHO classification 2021.\n* No clinical evidence of extra-CNS metastases\n* Negative CSF cytology\n* No prior therapy for MB other than surgery\n* No other medical contraindications to chemotherapy:\n* No uncontrolled invasive fungal infection or other severe systemic infection requiring system\u002Fparental therapy\n* No other severe organ dysfunctions, which cannot be clinically controlled\n* No concomitant use with yellow fever vaccine and with live virus and bacterial vaccines\n* No demyelinating form of Charcot-Marie-Tooth syndrome\n* Assessment of hearing function completed\n* No evidence of cancer predisposition syndromes other than Gorlin syndrome or ELP1, GPR161 germline alterations.\n* Provided written informed consent by parent(s)\u002Fparent representative(s) by bridging chemotherapy\n* Patient should be enrolled within 28 days after diagnosis. Bridging chemotherapy can start as early as criteria for enrollment are met, and must start no later than 33 days after diagnosis\n\nExclusion Criteria for bridging chemotherapy:\n\n* One or more of the inclusion criteria for bridging chemotherapy are lacking\n* Other histology than SHH MB\n\nInclusion Criteria for randomization:\n\n* Patient has received bridging chemotherapy as described in this protocol\n* Patients with centrally reviewed SHH-activated MB, TP53-wt, according to WHO classification 2021\n* Absence of metastatic disease on central radiology review\n* Exclusion of TP53-mutation by DNA sequencing of the TP53-gene from tumor tissue by central review. Results from local institution will be accepted if raw data of this analysis is forwarded to the national central review institution\n* Confirmation of SHH activation by DNA methylation-based classification on central review. Results from local institution will be accepted if raw data of this analysis is forwarded to the national central review institution\n* No amplification of MYC (amplification of MYCN allowed). Array-based technologies (850k array, molecular inversion probe assay (MIP)), array-based comparative genomic hybridization (array-CGH) or next generation sequencing (NGS) DNA sequencing coverage MYC locus will be used. If these alternative assays give any indication of possible amplification, FISH will be performed on central review.\n* No other medical contraindications to chemotherapy:\n* No uncontrolled invasive fungal infection or other severe systemic infection requiring system\u002Fparental therapy\n* No other severe organ dysfunctions, which cannot be clinically controlled\n* No concomitant use with yellow fever vaccine and with live virus and bacterial vaccines\n* No demyelinating form of Charcot-Marie-Tooth syndrome\n* Retrospective assessment of pre-operative health-related QoL (HR-QoL) measured by Pediatric Quality of Life Inventory\n* Provided written informed consent by parent(s)\u002Fparent representative(s) for randomization\n\nExclusion criteria for randomization:\n\n-Patients are excluded from the interventional study if any of the following criteria are met:\n\n1. One or more of the inclusion criteria for randomization are lacking\n2. Patients with metastatic disease\n3. TP53-mutated SHH MB\n4. MYC amplified MB\n5. Pre-existing condition incompatible with scheduled therapy (e.g. Fanconi anemia)\n6. Patients with non-communicating hydrocephalus, e.g. due to perinatal intracranial haemorrhage, adueductal stenosis, or meningitis\n7. Contraindication for any components of the randomized therapies, including HDCT and intraventricular chemotherapy. Note: postperative hydrocephalus is not a contraindication for i.ventr. MTX.","5 Years",{"count":672,"type":22},96,[674],"PHASE3","This is a trial to compare neurocognitive outcomes in the intent-to-treat population 2.5 years after diagnosis between patients with newly diagnosed, non-metastatic, SHH-activated, TP53-wt, non-MYC amplified MF randomized to the interventional arms A (\"Head Start 4\") or B (HIT-SKK).",[30],"2025-12-17",{"date":679,"type":43},"2025-12-18",{"date":681,"type":22},"2026-07-01",{"date":683,"type":22},"2038-10",{"name":208,"class":73},{"id":686,"slug":687,"hasResults":12,"nctId":688,"briefTitle":689,"officialTitle":690,"acronym":4,"eligibilityCriteria":691,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":692,"targetDuration":4,"studyType":23,"phases":694,"briefSummary":695,"conditions":696,"keywords":715,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":677,"lastUpdatePostDateStruct":716,"startDateStruct":717,"completionDateStruct":719,"leadSponsor":721,"locationsCount":51},"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":693,"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.",[561,32,697,698,699,700,701,702,703,704,124,31,705,30,706,707,708,709,710,711,712,713,714],"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",[32,699,698,713,701],{"date":679,"type":43},{"date":718,"type":43},"2020-10-26",{"date":720,"type":22},"2026-12",{"name":722,"class":723},"Jazz Pharmaceuticals","INDUSTRY",{"id":725,"slug":726,"hasResults":12,"nctId":727,"briefTitle":728,"officialTitle":729,"acronym":730,"eligibilityCriteria":731,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":732,"enrollmentInfo":733,"targetDuration":4,"studyType":23,"phases":735,"briefSummary":737,"conditions":738,"keywords":4,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":742,"lastUpdatePostDateStruct":743,"startDateStruct":745,"completionDateStruct":747,"leadSponsor":749,"locationsCount":51},"100368775","phase-4-68-ga-dotatate-petmri-in-the-diagnosis-and-management-of-somatostatin-receptor-positive-cns-tumors-100368775","NCT04081701","68-Ga DOTATATE PET\u002FMRI in the Diagnosis and Management of Somatostatin Receptor Positive CNS Tumors.","68Ga(Gallium)-DOTATATE Positron Emission Tomography (PET)\u002FMRI in the Diagnosis and Management of Somatostatin Receptor Positive Central Nervous System CNS Tumors.","DOMINO-START","Inclusion Criteria:\n\n* ≥ 18 years of age\n* Diagnosis of meningioma based on pathology reports and suspected recurrence or residual disease based on standard-of-care MRI\n* Additionally, patients with other somatostatin receptor 2 positive brain tumors, including esthesioneuroblastoma, hemangioblastoma, medulloblastoma, paraganglioma, pituitary adenoma, and SSTR-positive systemic cancers metastatic to the brain will be considered for the purposes of obtaining feasibility data\n* As the investigator's institution, PET\u002FMRI scanner utilizes a 3 Tesla (T) magnet, patients who may be ineligible to undergo 3T MRI but may undergo 1.5 Tesla (T) MRI, will undergo a 1.5T MRI as per clinical standard-of-care and a Ga68-DOTATATE PET\u002FCT with the PET portion to be fused with the 1.5T MRI utilizing fusion software.\n\nExclusion Criteria:\n\n* Contraindications to gadolinium-based contrast agent\n* History of allergic reaction to Gallium-68-DOTATATE\n* Pregnancy","100 Years",{"count":734,"type":22},200,[736],"PHASE4","The study population consists of patients who undergo resection for somatostatin receptor-positive (SSTR-positive) CNS tumors, focusing on meningioma, and including esthesioneuroblastoma, hemangioblastoma, medulloblastoma, paraganglioma, pituitary adenoma, and SSTR-positive systemic cancers metastatic to the brain, such as small cell carcinoma of the lung. The study indication is to determine the diagnostic utility of 68Ga-DOTATATE PET\u002FMRI in the diagnosis and management of patients with SSTR-positive CNS tumors, specifically whether 68Ga-DOTATATE PET\u002FMRI demonstrates utility distinguishing between tumor recurrence and post-treatment change. To date, the utility of Ga-68-DOTATATE PET\u002FMRI in meningioma has not been explored. Investigators have over the past 3 months been able to accrue the largest case series of presently 12 patients in whom Ga-68-DOTATATE PET\u002FMRI demonstrated utility in the assessment of meningioma, including assessment for postsurgical\u002Fpostradiation recurrence, detection of additional lesions not visualized on MRI alone, and evaluation of osseous invasion. Based on this initial experience, investigators intend to study the impact of Ga-68-DOTATATE PET\u002FMRI in the assessment of the extent of residual tumor in patients status post meningioma resection, specifically in patients in whom tumor location limits resectability, patients with World Health Organization (WHO) grade II\u002FIII disease, and patients with history of stereotactic radiosurgery (SRS) who develop postradiation change.",[739,185,311,740,30,302,741],"CNS Tumors","Hemangioblastoma","Pituitary Adenoma","2025-11-17",{"date":744,"type":43},"2025-11-21",{"date":746,"type":43},"2019-09-04",{"date":748,"type":22},"2038-12-31",{"name":750,"class":73},"Weill Medical College of Cornell University",{"id":752,"slug":753,"hasResults":12,"nctId":754,"briefTitle":755,"officialTitle":756,"acronym":757,"eligibilityCriteria":758,"healthyVolunteers":12,"sex":17,"minAge":670,"maxAge":84,"enrollmentInfo":759,"targetDuration":4,"studyType":149,"phases":4,"briefSummary":760,"conditions":761,"keywords":762,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":767,"lastUpdatePostDateStruct":768,"startDateStruct":770,"completionDateStruct":772,"leadSponsor":774,"locationsCount":51},"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",{"count":734,"type":22},"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).",[34,30,29,31],[562,763,764,765,766],"Radiotherapy","Proton Beam Therapy","Neuro-cognition","Bio-markers","2025-04-08",{"date":769,"type":43},"2025-04-11",{"date":771,"type":43},"2025-02-11",{"date":773,"type":22},"2032-02",{"name":775,"class":73},"Tata Memorial Centre",{"id":777,"slug":778,"hasResults":12,"nctId":779,"briefTitle":780,"officialTitle":781,"acronym":782,"eligibilityCriteria":783,"healthyVolunteers":12,"sex":17,"minAge":462,"maxAge":84,"enrollmentInfo":784,"targetDuration":4,"studyType":149,"phases":4,"briefSummary":786,"conditions":787,"keywords":4,"overallStatus":161,"whyStopped":4,"lastUpdateSubmitDate":789,"lastUpdatePostDateStruct":790,"startDateStruct":792,"completionDateStruct":794,"leadSponsor":796,"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.",{"count":785,"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.",[788,186,30,31],"Glioma, Malignant","2025-03-24",{"date":791,"type":43},"2025-03-25",{"date":793,"type":22},"2025-05",{"date":795,"type":22},"2026-03",{"name":797,"class":73},"University Hospital Regensburg"]