[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"central-nervous-system-neoplasms\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:central-nervous-system-neoplasms":33},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,4,0,[8,49,79,117],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":26,"conditions":27,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":37,"lastUpdatePostDateStruct":38,"startDateStruct":41,"completionDateStruct":43,"leadSponsor":45,"locationsCount":48},"100468924","phase-1-study-of-abemaciclib-and-elacestrant-in-participants-with-brain-metastasis-due-to-erher-2--breast-cancer-100468924",false,"NCT05386108","Study of Abemaciclib and Elacestrant in Participants With Brain Metastasis Due to ER+\u002FHER-2- Breast Cancer","An Open-label Multicenter Phase 1b-2 Study of Elacestrant in Combination With Abemaciclib in Women and Men With Brain Metastasis From Estrogen Receptor Positive, HER-2 Negative Breast Cancer","ELECTRA","Inclusion Criteria:\n\n1. Participant has the signed informed consent form before any study-related activities according to local guidelines.\n2. Women or men aged ≥18 years, at the time of informed consent signature.\n\n   * Female participants may be either postmenopausal or pre\u002Fperimenopausal. Postmenopausal status is defined by:\n\n     1. Age ≥60 years\n     2. Age \\\u003C60 years and amenorrhea for 12 or more months without an alternative cause) and follicle stimulating hormone and estradiol in postmenopausal ranges per local reference ranges\n     3. Documentation of prior bilateral oophorectomy, at least 1 month before first dose of trial therapy).\n   * Pre-menopausal \u002F peri-menopausal women and men must be concurrently receiving a luteinizing hormone-releasing hormone (LHRH) agonist starting at least 3-4 weeks before the start of trial therapy and is planning to continue LHRH during the study.\n3. Participant must have ER-positive, HER-2 negative tumor status as confirmed by local laboratory testing in the following manner:\n\n   * Documentation of ER positive tumor with ≥ 1% staining by immunohistochemistry (IHC) as defined in the 2010 or 2020 American Society for Clinical Oncology (ASCO) recommendations for ER testing, with or without progesterone receptor (PGR) positivity\n   * HER-2 negative tumor with an IHC result of 0 or 1+ for cellular membrane protein expression or an in situ hybridization negative result as defined in the 2013 or 2018 ASCO recommendations for HER-2 testing\n4. In Phase 2, participants must have at least one active and measurable brain metastasis per RECIST version 1.1.\n\n   * Any of the following qualifies brain metastases as active:\n\n     1. Newly diagnosed brain metastasis in participants who never received prior central nervous system (CNS)-directed therapy.\n     2. Newly diagnosed brain metastasis outside any area that was previously subjected to CNS-directed therapy.\n     3. Brain metastases demonstrating unequivocal progression in the opinion of the treating investigator in an area that has previously been subjected to CNS-directed therapy.\n   * For lesions, including brain metastases, to qualify as measurable, and possibly be selected as target lesions, per RECIST version 1.1, the longest diameter must be ≥10 millimeters \\[mm\\] by computed tomography \\[CT\\] or magnetic resonance imaging \\[MRI\\]).\n   * In Phase 1b, the presence of brain metastases is allowed but not required for eligibility, in this case, at least 1 measurable lesion outside the brain is required.\n5. Participants receiving concomitant corticosteroids must be on a stable or decreasing dose for at least 7 days prior to baseline and not receiving doses higher than 4 mg of dexamethasone per day or equivalent.\n6. Participants have experienced no more than one seizure within 4 weeks prior to starting trial therapy.\n7. Participants' prior therapy received in the metastatic setting includes:\n\n   * At least one endocrine therapy\n   * Up to two chemotherapy regimens\n   * Up to two lines of prior cyclin-dependent kinase (CDK) 4\u002F6 inhibitor, not including abemaciclib\n\n   Note 1: Toxicity from prior therapy must be resolved to NCI CTCAE version 5.0 Grade ≤1, with the exception of alopecia and peripheral sensory neuropathy (Grade ≤2).\n\n   Note 2: Chemotherapy refers to not targeted cytotoxic agents (for example, alkylating agents, taxanes, nucleotide analogs, platinum-based drugs, vinca alkaloids, etc) and antibody drug conjugates (ADCs). Targeted therapies (for example, kinase inhibitors) are not considered chemotherapy for eligibility purposes. Not targeted cytotoxic agents administered for less than 1 cycle will not be counted as a prior chemotherapy regimen.\n8. Participant has documented intracranial and\u002For extracranial radiological progression or recurrence while on or after the most recent therapy.\n9. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2\n10. Participant has a life expectancy ≥ 12 weeks.\n11. Participant has adequate bone marrow and organ function, as defined by the following laboratory values:\n\n    1. Absolute neutrophil count (ANC) ≥1.5 × 10\\^9\u002Fliter (L)\n    2. Platelets ≥100 × 10\\^9\u002FL\n    3. Hemoglobin ≥9.0 grams (g)\u002Fdeciliter (dL)\n    4. Potassium, sodium, calcium (corrected for serum albumin) and magnesium CTCAE Grade ≤1 (if screening assessments are abnormal, these assessments may be repeated up to 2 times; participants may receive appropriate supplementation or treatment prior to reassessment)\n    5. Creatinine clearance (per Cockcroft-Gault formula) ≥50 mL\u002Fminute\n    6. Serum albumin ≥3.0 g\u002FdL (≥30 g\u002FL)\n    7. Liver function tests:\n\n       In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 × upper limit of normal (ULN). If the participant has liver metastases, ALT and AST ≤5.0 × ULN.\n    8. Total serum bilirubin \\\u003C1.5 × ULN except for participants with Gilbert's syndrome who may be included if the total serum bilirubin is ≤3.0 × ULN or direct bilirubin ≤ 1.5 × ULN\n12. The participant is willing and able to adhere to the study visit schedule and other protocol requirements.\n\nExclusion Criteria:\n\n1. Immediate CNS-specific treatment is likely to be required, per the treating physician's assessment.\n2. Participant has imminent organ failure and\u002For visceral crisis.\n3. Participant has leptomeningeal metastases, defined as having positive cerebrospinal fluid (CSF) cytology or unequivocal radiologic and clinical evidence of leptomeningeal involvement. Note: Discrete dural metastases are permitted.\n4. Breast cancer treatment-naïve participants (that is, not having received any systemic therapy) in the advanced\u002Fmetastatic setting.\n5. History of pulmonary embolism (PE), cardiovascular accident (CVA), myocardial infarction (MI) in the past 6 months from screening visit.\n6. Prior therapy with abemaciclib in the metastatic setting. Note: Use of abemaciclib in the adjuvant setting is allowed if the last treatment administration was more than 12 months prior to first recurrence.\n7. Prior therapy with elacestrant or other investigational selective estrogen receptor degraders (SERDs), or investigational alike agents such as selective estrogen receptor modulators (SERMs), selective estrogen receptor covalent antagonists (SERCANs), complete estrogen receptor antagonists (CERANs), and proteolysistargeting chimeras (PROTACs) in the metastatic setting.\n8. Participant has a concurrent malignancy or malignancy within 3 years of enrollment, with the exception of adequately treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or second primary breast cancer; and any other malignancy that is considered in complete remission by the Investigator(s) that is approved by the Medical Monitor.\n9. Currently participating in another breast cancer intervention clinical study. Participants who are being followed for overall survival for another clinical trial with no therapy and study intervention are allowed after the washout period for any prior therapy.\n10. Prior anti-cancer or investigational drug treatment within the following windows:\n\n    * Fulvestrant treatment (last injection) \\\u003C42 days before first dose of study drug\n    * Any other endocrine therapy \\\u003C14 days before first dose of study drug. Note: LHRH agonists should not be counted as endocrine therapy.\n    * Chemotherapy or other anti-cancer therapy \\\u003C14 days before first dose of study drug\n    * Any investigational anti-cancer drug therapy within \\\u003C28 days or \\\u003C5 half lives, whichever is shorter\n    * Bisphosphonates or receptor activator of nuclear factor-κB ligand (RANKL) inhibitors initiated, or dose changed \\\u003C1 month prior to first dose of study drug according to institutional guidelines.\n11. Radiation therapy (including CNS directed) within 7 days before the first dose of study drug or without a full recovery from radiotherapy acute effects.\n12. Uncontrolled significant active infections\n\n    * Participants with hepatitis B virus (HBV) and\u002For hepatitis C virus (HCV) infection must have undetectable viral load (or detected below the lower limit of quantification) during screening\n    * Participants known to be human immunodeficiency virus positive (HIV+) are allowed as long as they have undetectable viral load (viral suppression) at baseline.\n13. Major surgery within 4 weeks of starting trial therapy.\n14. Inability to take oral medication, or history of malabsorption syndrome or any other uncontrolled gastrointestinal condition that may significantly alter the absorption of study drugs.\n15. Females of childbearing potential who do not agree to use a highly effective non-hormonal method of contraception and to abstain from donating ova within 28 days of the first dose of study treatment through 120 days after the last dose of study treatment. Highly effective non-hormonal method of contraception includes any of the following:\n\n    1. Intrauterine device (non-hormonal)\n    2. Sexual abstinence\n    3. Bilateral tubal occlusion\u002Fligation\n    4. Have a vasectomized partner with confirmed azoospermia.\n16. Male participants (including males after a vasectomy) with a pregnant or non-pregnant female of childbearing potential partner who do not agree to use a highly effective barrier contraception method (condoms) within 28 days of the first dose of study treatment until 120 days of the last dose of study treatment. And male participants who do not agree to abstain from freezing or donating sperm within the same period. In addition, female partners of childbearing potential, of male participants (who has not undergone vasectomy) must use highly effective methods of contraception.\n17. Females who are pregnant or breastfeeding. Females should not get pregnant during study treatment and for 120 days after last dose of study treatment. Females should not breastfeed during administration of elacestrant and for 1 week after receiving the last dose.\n18. Known intolerance to either study drug or any of their excipients.\n19. Participants currently receiving or received any of the following medications prior to first dose of trial therapy:\n\n    1. Known strong or moderate inducers or inhibitors of cytochrome P450 (CYP) 3A4 (including foods and herbal preparations) within 14 days or \\\u003C5 half-lives, whichever is shorter)\n    2. Herbal preparations\u002Fmedications (which are not strong or moderate inducers or inhibitors of CYP3A4). These include, but are not limited to, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng within 7 days prior to initiating trial therapy\n    3. Vaccination, including but not limited to vaccination against coronavirus disease-19 (COVID-19), during the 7 days prior to randomization.\n20. Any severe medical or psychiatric condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study.","ALL","18 Years",{"count":20,"type":21},73,"ESTIMATED","INTERVENTIONAL",[24,25],"PHASE1","PHASE2","This is a multi-site, global, open-label study that includes a phase 1b evaluation of elacestrant in combination with abemaciclib in women and men with brain metastases from estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER-2) negative breast cancer. Phase 1b was designed to select the recommended phase 2 dose (RP2D) and is followed by an ongoing phase 2 evaluation of elacestrant in combination with abemaciclib in participants with active brain metastases from ER-positive, HER-2 negative breast cancer.",[28,29,30,31,32,33,34,35],"Breast Neoplasms","Brain Neoplasms","Neoplasms by Site","Neoplasms","Breast Diseases","Central Nervous System Neoplasms","Brain Diseases","Central Nervous System Diseases","RECRUITING","2026-06-03",{"date":39,"type":40},"2026-06-04","ACTUAL",{"date":42,"type":40},"2022-08-31",{"date":44,"type":21},"2026-12",{"name":46,"class":47},"Stemline Therapeutics, Inc.","INDUSTRY",86,{"id":50,"slug":51,"hasResults":11,"nctId":52,"briefTitle":53,"officialTitle":54,"acronym":4,"eligibilityCriteria":55,"healthyVolunteers":11,"sex":17,"minAge":4,"maxAge":56,"enrollmentInfo":57,"targetDuration":4,"studyType":22,"phases":59,"briefSummary":60,"conditions":61,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":68,"lastUpdatePostDateStruct":69,"startDateStruct":71,"completionDateStruct":73,"leadSponsor":75,"locationsCount":78},"100503471","phase-1-loc3car-locoregional-delivery-of-b7-h3-car-t-cells-for-pediatric-patients-with-primary-cns-tumors-100503471","NCT05835687","Loc3CAR: Locoregional Delivery of B7-H3-CAR T Cells for Pediatric Patients With Primary CNS Tumors","Loc3CAR: Locoregional Delivery of B7-H3-specific Chimeric Antigen Receptor Autologous T Cells for Pediatric Patients With Primary CNS Tumors","Inclusion Criteria: Screening Eligibility\n\n1. Age ≤ 21 years of age\n2. Primary CNS tumor\n3. For Cohort A, must have evidence of relapsed or refractory non-brainstem CNS tumor\n4. For Cohort B, must meet one of the following criteria:\n\n   * Adequate tumor tissue from primary tumor resection or biopsy for central pathology review (i.e., B7-H3 expression evaluation by immunohistochemistry \\[IHC\\] or H3K27M mutation if pontine lesion)\n   * Has a diagnosis of diffuse midline glioma that harbors a mutation associated with this entity (e.g. H3K27M)\n   * Has presumptive\u002Fsuspected brainstem high-grade neoplasm with available imaging for central imaging review\n5. Life expectancy of \\> 12 weeks\n6. Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines\n\nExclusion Criteria: Screening Eligibility All Participants\n\n1\\. Participant has other clinically significant medical disorders (e.g. serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that could compromise their ability to tolerate protocol therapy or would interfere with study procedure.\n\nInclusion Criteria: Procurement and T-cell Production Eligibility\n\n1. Age ≤ 21 years of age\n2. Primary CNS tumor with measurable or evaluable disease and meets criteria for either Cohort A or B:\n\n   * Cohort A: relapsed\u002Frefractory non-brainstem CNS primary tumor AND tumor is B7-H3 positive\n   * Cohort B: Diffuse midline glioma AND tumor is:\n\n     * B7-H3 positive if non-pontine\n     * OR H3K27-altered diffuse midline pontine glioma\n     * OR radiographically-confirmed classic\u002Ftypical DIPG\n3. Estimated life expectancy of \\>12 weeks\n4. Karnofsky or Lansky performance score ≥50\n5. Participant of childbearing\u002Fchild-fathering potential agrees to use contraception\n6. For females of childbearing age:\n\n   * Not pregnant with negative serum pregnancy test\n   * Not lactating with intent to breastfeed\n7. Chemotherapy\u002Fbiologic therapy must be discontinued ≥ 7 days prior to enrollment\n8. The last dose of antibody therapy (including check point inhibitor) must be at least 3 half-lives or 30 days, whichever is shorter, from the time of enrollment\n9. At least 30 days from most recent cell infusion prior to enrollment.\n10. All systemically administered corticosteroid therapy must be stable or decreasing for ≥1 week prior to enrollment, with a maximum dexamethasone dose of 2.8 mg\u002Fm\\^2\u002Fday\n11. Meets eligibility for apheresis, or has an apheresis product previously collected at a FACT-accredited program\n12. Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines\n\nExclusion Criteria: Procurement and T-cell Production Eligibility\n\n1. Known primary immunodeficiency or acquired immunodeficiency.\n2. Known HIV positivity\n3. Severe intercurrent bacterial, viral or fungal infection (e.g. active hepatitis B or C infection or adenovirus infection).\n4. Rapidly progressive disease\n5. Known underlying medical condition for which participation in this trial would not be in the best interest of the participant or that could prevent, limit or confound protocol assessments.\n6. Adult patient, Parent, or legal guardian is unwilling or unable to provide consent for participation in a 15 year long-term follow up study.\n\nInclusion Criteria: Treatment Eligibility\n\nCohort A\n\n* Relapsed\u002Frefractory non-brainstem CNS primary tumor\n* Tumor must be considered B7-H3 positive\n\nCohort B\n\n* Diffuse Midline Glioma - Must meet one of the following criteria\n\n  * Tumor is considered B7-H3 positive\n  * H3K27-altered diffuse midline pontine glioma\n  * Radiographically-confirmed classic\u002Ftypical DIPG\n* Must complete standard radiation prior to Loc3CAR treatment and be a minimum of 6 weeks post-completion of radiation therapy\n\nAll participants\n\n1. Age ≤ 21 years old\n2. Primary CNS tumor with measurable or evaluable disease\n3. Available autologous T-cell product that has met GMP release criteria\n4. Participant has a CNS reservoir catheter (e.g., Ommaya) or programmable shunt\n5. First CAR T cell infusion is planned\u002Fscheduled ≥ 5 days from CNS surgery, including catheter placement\n6. The following treatments must be discontinued for the specified duration prior to treatment enrollment:\n\n   * Radiation therapy: ≥ 6 weeks\n   * Bevacizumab: ≥ 28 days\n   * Cytotoxic chemotherapy: ≥ 21 days\n   * Biologic agents: ≥ 7 days\n   * Antibody therapy: ≥ 3 half-lives or 30 days (whichever is shorter)\n   * Cellular therapy: ≥ 30 days\n   * Investigational agent: ≥ 3 half-lives or 30 days (whichever is shorter)\n   * Corticosteroids: All systemically administered therapy must be stable or decreasing for ≥ 1 week prior to enrollment, with a maximum dexamethasone dose of 2.8 mg\u002Fm\\^2\u002Fday. Corticosteroid physiologic replacement therapy for management of pituitary\u002Fadrenal axis insufficiency and\u002For topical administration (e.g. inhaled or dermatologic) is allowed.\n7. Estimated life expectancy of \\>8 weeks\n8. Karnofsky or Lansky performance score ≥ 50\n9. Echocardiogram with a left ventricular ejection fraction ≥ 50%\n10. Adequate renal function defined as calculated creatinine clearance or radioisotope GFR ≥ 50 mL\u002Fmin\u002F1.73m\\^2.\n11. Adequate pulmonary function defined as forced vital capacity (FVC) ≥50% of predicted value or pulse oximetry ≥90% on room air.\n12. Total Bilirubin ≤3 times the upper limit of normal for age.\n13. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 times the upper limit of normal for age.\n14. Hemoglobin \\>8.0 g\u002FdL (can be transfused).\n15. Platelet count \\>50,000\u002Fmm\\^3 (can be transfused).\n16. Absolute neutrophil count (ANC) ≥1000\u002FuL.\n17. Taking anti-seizure medication, or agrees to initiate anti-seizure medication prior to starting study therapy.\n18. Has recovered from all NCI CTAE grade III-IV, non-hematologic acute toxicities from prior therapy.\n19. Male participants of child-fathering potential agree to use contraception\n20. Female participants of childbearing potential:\n\n    * Negative serum pregnancy test within 7 days prior to infusion\n    * Not lactating with intent to breastfeed\n    * If sexually active, agrees to use birth control until 3 months after T-cell infusion. Male partners should use a condom\n21. Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines\n\nExclusion Criteria: Treatment Eligibility-All Participants\n\n1. Participant has a non-programmable ventricular shunt that could compromise study therapy\n2. Participant has a reservoir catheter or shunt in a location that could compromise study therapy or patient safety\n3. Known primary immunodeficiency or acquired immunodeficiency.\n4. Known HIV positivity\n5. Severe intercurrent bacterial, viral or fungal infection\n6. Myocardial infarction, unstable angina, New York Heart Association class III and IV congestive heart failure, myocarditis, or ventricular arrhythmias requiring medication within 6 months prior to study entry\n7. Receiving therapy as outlined above during the 'wash-out' period\n8. Rapidly progressing disease\n9. Received any live vaccines within 30 days\n10. Known underlying medical condition for which participation in this trial would not be in the best interest of the participant or that could prevent, limit or confound protocol assessments\n11. Adult patient, Parent, or legal guardian is unwilling or unable to provide consent for participation in a 15 year long-term follow up study\n12. Evidence of uncontrolled hypertension. Anti-hypertensive medications are permitted if on a stable dose.\n13. Uncontrolled seizures","21 Years",{"count":58,"type":21},48,[24],"Loc3CAR is a Phase I clinical trial evaluating the use of autologous B7-H3-CAR T cells for participants ≤ 21 years old with primary CNS neoplasms. B7-H3-CAR T cells will be locoregionally administered via a CNS reservoir catheter. Study participants will be divided into two cohorts: cohort A with B7-H3-positive relapsed\u002Frefractory non-brainstem primary CNS tumors, and cohort B with diffuse midline gliomas (DMG). Participants will receive four (4) B7-H3-CAR T cell infusions over a 4 week period. The purpose of this study is to find the maximum (highest) dose of B7-H3-CAR T cells that are safe to give patients with primary brain tumors.\n\nPrimary objectives\n\n* To determine the safety, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for the locoregional delivery of autologous B7-H3-CAR T cells in patients ≤ 21 years of age with recurrent\u002Frefractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B).\n\nSecondary objectives\n\n* To assess the efficacy, defined as sustained objective response, a partial response (PR) or complete response (CR) observed anytime on active treatment with B7-H3-CAR T cells in patients with relapsed\u002Frefractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B).\n* To characterize and monitor neurologic toxicities in patients while on study (Cohort A and B).",[33,62,63,64,65,66,67],"Atypical Teratoid\u002FRhabdoid Tumor","Diffuse Midline Glioma, H3 K27M-Mutant","Ependymoma","High Grade Glioma","Glioblastoma","Medulloblastoma","2026-05-01",{"date":70,"type":40},"2026-05-05",{"date":72,"type":40},"2023-04-27",{"date":74,"type":21},"2028-03",{"name":76,"class":77},"St. Jude Children's Research Hospital","OTHER",1,{"id":80,"slug":81,"hasResults":11,"nctId":82,"briefTitle":83,"officialTitle":84,"acronym":4,"eligibilityCriteria":85,"healthyVolunteers":11,"sex":17,"minAge":86,"maxAge":56,"enrollmentInfo":87,"targetDuration":4,"studyType":22,"phases":89,"briefSummary":90,"conditions":91,"keywords":102,"overallStatus":106,"whyStopped":4,"lastUpdateSubmitDate":107,"lastUpdatePostDateStruct":108,"startDateStruct":110,"completionDateStruct":112,"leadSponsor":114,"locationsCount":116},"100622970","phase-1-b7-h3cd28zcart-in-cns-neoplasms-100622970","NCT07390539","B7-H3.CD28Z.CART in CNS Neoplasms","A Phase 1\u002F1b Study of Autologous b7-h3 Chimeric Antigen Receptor t Cells (b7-h3.cd28z.Cart) in Children and Young Adults With Recurrent or Progressive Cns Neoplasms Expressing b7-h3 Target","Pre-screening Inclusion Criteria:\n\n* Participants must have histologically and\u002For molecularly confirmed CNS embryonal tumor (see eligible tumor types below), OR ependymoma that is recurrent\u002Fprogressive following standard of care treatment.\n\n  --Eligible CNS embryonal tumor types include:\n  * Medulloblastoma\n  * Atypical Teratoid Rhabdoid Tumor (ATRT)\n  * Embryonal Tumor with Multilayered Rosettes (ETMR) Pineoblastoma\n  * Other CNS embryonal tumor types, at the discretion of the study chair (or designee)\n* Participants must have adequate pre-trial tumor material available to determine B7- H3 expression status. Tumor tissue from the most recent resection or biopsy of recurrent disease is preferred. If unavailable, tumor tissue from prior recurrences or from time of initial diagnosis is acceptable. Biopsies will not be performed for participation in this research trial or for research purposes.\n* Pre-screening IHC Consent: All participants ≥ 18 years of age must be able to give informed consent. For participants \\\u003C18 years of age, their legal authorized representative (LAR) (i.e. parent or guardian) must give informed consent. Pediatric participants will be included in age-appropriate discussion and written assent will be obtained for those ≥10 years of age, where appropriate. If a minor becomes of age during participation of this study, they will be asked to reconsent as an adult.\n\nInclusion Criteria:\n\n* Participants must have histologically and\u002For molecularly confirmed CNS embryonal tumor (see eligible tumor types below), OR ependymoma that is recurrent\u002Fprogressive following standard of care treatment.\n\n  --Eligible CNS embryonal tumor types include:\n  * Medulloblastoma\n  * Atypical Teratoid Rhabdoid Tumor (ATRT)\n  * Embryonal Tumor with Multilayered Rosettes (ETMR)\n  * Pineoblastoma\n  * Other CNS embryonal tumor types, at the discretion of the study chair (or designee)\n* B7-H3 expression: Demonstration of B7-H3 expression with H score greater than 100 by immunohistochemistry (IHC) is required.\n* Age: greater than or equal to two (2) years of age and less than or equal to 21 years of age. The first participant treated at each dose level within each stratum (Standard Risk and High Risk) will be ≥ 6 years of age when feasible.\n* Disease status: Participants must have evaluable disease in the central nervous system to be eligible. Evaluable disease includes either measurable OR non-measurable disease, defined as follows:\n\n  --Measurable disease (contrast-enhancing or non-enhancing tumor)\n  * Clearly defined lesional margins with two perpendicular diameters of at least 10mm, OR\n  * At least two times (in both perpendicular diameters) the MRI slice thickness, plus the interslice gap\n\n    --Non-measurable disease (tumor that is too small to be accurately measured)\n  * Lesion that is measurable in only one perpendicular dimension, OR\n  * Lesion that is less than 10mm in at least one perpendicular dimension, OR\n  * Lesion that is less than two times the MRI slice thickness, plus the interslice gap\n  * Note: Leptomeningeal (LM) disease is considered non-measurable but evaluable.\n* Performance status: Karnofsky performance status ≥60% for participants ≥16 years of age and Lansky performance status ≥60% for participants \\\u003C16 years of age (see APPENDIX A PERFORMANCE STATUS CRITERIA). NOTE: Participants with neurologic deficits must have a stable neurologic exam for seven (7) days prior to enrollment. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n* Life expectancy of greater than 12 weeks\n* Prior therapy: Participants must have received prior standard of care therapy, including maximal safe surgical resection, radiation therapy and\u002For standard chemotherapy, and is recovered from all acute treatment-related toxicities (defined as ≤ Grade 1 or stable) from all prior therapy before entering this study There is no upper limit to the number of prior therapies allowed, but must have received all standard curative options for their tumor type.\n* Participants must meet the following washouts prior to enrollment:\n\n  * Radiation therapy - Participants must have had their last fraction of:\n\n    ---Craniospinal irradiation, whole brain radiation therapy, or radiation therapy to \\>50% of the pelvis or spine \\>28 days prior to enrollment\n\n    ---Focal irradiation (small port) \\>14 days prior to enrollment\n  * At least 14 days since any prior cytotoxic chemotherapy\n  * At least 7 days since any biologic antineoplastics, tyrosine kinase inhibitor, targeted agent\n  * At least 21 days or 5 half-lives (whichever is shorter) since any investigational antineoplastic or disease-directed agent (but at least 28 days from prior investigational antineoplastic vaccine therapy)\n  * At least 21 days since any monoclonal antibody therapy\n  * At least 90 days since any systemic inhibitor\u002Fstimulatory immune checkpoint therapy\n  * At least 28 days from prior autologous stem cell transplantation, with no ongoing toxicities\n  * At least 14 days after peg-filgrastim and 7 days for hematopoietic growth factor support\n* Steroid use: Must not require concurrent systemic steroid therapy, although physiologic corticosteroid replacement therapy for management of pituitary\u002Fadrenal insufficiency and\u002For topical administration (e.g. inhaled or dermatologic) is allowed. Use of topical, ocular, intranasal, or inhaled corticosteroids are permitted per PI\n\ndiscretion.\n\n* Participants must have adequate organ function, as defined below\n\n  --Adequate bone marrow function\n  * Hemoglobin ≥ 8 g\u002FdL\n  * Absolute neutrophil count (ANC) ≥ 1000 cells\u002FuL\n  * Absolute lymphocyte count (ALC) ≥ 150 cells\u002FuL\n  * Platelets ≥100,000\u002FuL (unsupported, defined as no platelet transfusion within 4 days)\n* Adequate renal function defined as creatinine within normal limits for age OR creatinine clearance (as estimated by Cockcroft Gault Equation for participants ≥ 18yo and Bedside Schwartz for participants \\\u003C18yo) ≥70mL\u002Fmin\n\n  * Maximum Serum Creatinine mg\u002FDL ---6 months to 1 year Male 0.5 Female 0.5 ---1 to \\\u003C 2 years Male 0.6 Female 0.6 ---2 to \\\u003C 6 years Male 0.8 Female 0.8\n\n    * 6 to \\\u003C 10 years Male 1 Female 1\n    * 10 to \\\u003C 13 years Male 1.2 Female 1.2\n    * 13 years to \\\u003C 16 years Male 1.5 Female 1.4\n\n      * 16 years Male 1.7 Female 1.4\n* Adequate hepatic function\n\n  * Serum ALT\u002FAST ≤3.0 upper limit of normal (ULN)\n  * Total bilirubin ≤1.5mg\u002FdL, except in subjects with confirmed Gilbert's syndrome\n* Adequate cardiac function\n\n  --Ejection fraction ≥50% or fractional shortening ≥28%, measured by echocardiography\n* Adequate pulmonary function\n\n  * No evidence of dyspnea at rest\n  * Pulse oximetry \\>92% whilst breathing room air\n* Adequate neurologic function\n\n  * Participants with seizure disorders on anticonvulsants may be enrolled if seizures are well controlled (no seizure activity within 7 days prior to enrollment)\n  * Nervous system disorders (CTCAE v6.0) resulting from prior therapy must be ≤ Grade 2, with the exception of decreased tendon reflex (DTR; any Grade eligible). Participants with neurological deficits should be stable for a minimum of 7 days prior to enrollment. (A baseline detailed neurological exam should clearly document the neurological status of the participant prior at enrollment).\n* Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization are not considered to be of childbearing potential)\n* Participants of childbearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for one year after receiving the preparative lymphodepletion regimen, or for as long as B7- H3.CD28Z.CART cells are detectable in peripheral blood or CSF, whichever is later.\n* Participant or parent of participant or legally recognized representative must be able to sign a written informed consent document. Pediatric participants will be included in age-appropriate discussion and written assent will be obtained for those ≥10 years of age, where appropriate.\n\nExclusion Criteria:\n\n* Participants with bulky tumor are ineligible. Bulky tumor is defined as:\n\n  * Tumor with diameter of \\>5cm in one dimension on T2\u002FFLAIR sequence\n  * Tumor with evidence of clinically significant midline shift or uncal herniation\n  * Tumor that, in opinion of the site investigator, shows significant mass effect in either the brain or spine\n* Participants with clinical or radiological evidence of brain herniation.\n* Participants who have received other B7-H3 targeted cellular therapies. Other prior cellular therapies are eligible, including immune checkpoint inhibition and vaccine therapy. These prior therapies should be discussed with the study chair (or designee) prior to participant enrollment.\n* Concurrent illness\n\n  * Participants with any prior immunodeficiency or history of autoimmune disease requiring systemic steroids\u002F immunosuppressive medication\u002F disease-modifying agents within the last two (2) years.\n  * Uncontrolled (Grade 3) bacterial, viral, fungal, or other infection.\n  * Ongoing infection with HIV or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive). A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and\u002For nucleic acid testing.\n  * Evidence of severe or uncontrolled systemic disease (e.g. Grade 3 significant cardiac, pulmonary, hepatic, renal or other organ dysfunction) that in the judgement of the principal investigator is likely to interfere with assessment of safety or efficacy of the investigational regimen and its requirements.\n  * Known sensitivity or allergy to any of the agents\u002Freagents used in this study (i.e. DSMO, cyclophosphamide, fludarabine)\n  * History of severe hypersensitivity reaction to compounds of similar chemical or biologic compositions to any agent used in the study or in the manufacturing of cells.\n* Concomitant medications\n\n  * Current systemic corticosteroid therapy\n  * Note, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency will be allowed.\n  * Participants who are receiving any other anti-cancer or investigational drug therapy are ineligible.\n  * Participants who have received the last vaccination of a live vaccine ≤ 30 days prior to the start of treatment are ineligible.\n  * Ongoing use of dietary supplements, alternative therapies or extreme diets, or any medication not approved by the study chair (or designee).\n* Any other condition which in the principal investigator's opinion makes the individual clinically unsuitable to participate in this trial, or which would jeopardize compliance with the protocol, or would make it difficult to interpret adverse events or study data.","2 Years",{"count":88,"type":21},70,[24],"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)",[33,92,93,94,95,67,96,97,98,64,62,99,100,101],"Brain Tumor","Brain Tumor, Recurrent","Brain Tumor, Pediatric","Brain Tumor Adult","Medulloblastoma, Childhood","Medulloblastoma, Adult","Medulloblastoma Recurrent","Embryonal Tumor With Multilayered Rosettes","Pineoblastoma","Leptomeningeal Disease",[33,92,94,103,104,67,96,97,98,64,62,105,100,101],"Brain Tumor, Adult","Brain Tumor Recurrent","Embryonal Tumor with Multilayered Rosettes","NOT_YET_RECRUITING","2026-01-28",{"date":109,"type":40},"2026-02-05",{"date":111,"type":21},"2026-07",{"date":113,"type":21},"2032-08-31",{"name":115,"class":77},"Robbie Majzner",2,{"id":118,"slug":119,"hasResults":11,"nctId":120,"briefTitle":121,"officialTitle":122,"acronym":4,"eligibilityCriteria":123,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":124,"targetDuration":4,"studyType":22,"phases":126,"briefSummary":127,"conditions":128,"keywords":147,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":148,"lastUpdatePostDateStruct":149,"startDateStruct":151,"completionDateStruct":153,"leadSponsor":154,"locationsCount":78},"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":125,"type":21},102,[24],"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.",[33,66,129,130,131,132,133,134,135,136,63,64,137,67,138,139,140,141,142,143,144,145,146],"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",[66,131,130,145,133],"2025-12-17",{"date":150,"type":40},"2025-12-18",{"date":152,"type":40},"2020-10-26",{"date":44,"type":21},{"name":155,"class":47},"Jazz Pharmaceuticals"]