[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"Sabine Mueller, MD, PhD\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":158},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,5,0,[8,44,79,106,133],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":29,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":32,"lastUpdatePostDateStruct":33,"startDateStruct":36,"completionDateStruct":38,"leadSponsor":40,"locationsCount":43},"100627318","phase-2-study-of-novel-therapies-for-young-people-with-recurrentprogressive-atypical-teratoid-rhabdoid-tumor-atrt-100627318",false,"NCT07447076","Study of Novel Therapies for Young People With Recurrent\u002FProgressive Atypical Teratoid Rhabdoid Tumor (ATRT)","A Platform Study of Novel Therapies for Children, Adolescents and Young Adults With Recurrent\u002FProgressive Atypical Teratoid Rhabdoid Tumor (ATRT)","Inclusion Criteria:\n\n* In addition to the below, investigators are to refer to arm-specific inclusion criteria in the appendix.\n\n  * Participants must have a pathologic diagnosis of central nervous system (CNS) ATRT, with confirmation of SWI\u002FSNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily b, member 1 (SMARCB1) (INI1) loss by immunohistochemistry (IHC) and\u002For biallelic loss of function of SMARCB1 by molecular report. Loss of SWI\u002FSNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily A, Member 4 (SMARCA4) as confirmed by IHC or molecular report is also acceptable but requires study chair approval.\n  * Participants must have confirmation of methylation report, co-enrollment on PNOC-030 or sufficient tumor tissue available for methylation-based subgrouping\n  * Participants must have recurrent or progressive ATRT.\n  * Participants age must be ≥1 and ≤ 39 years at the time of study enrollment. Please refer to arm specific inclusion criteria for potential variations in lower age eligibility limit.\n  * Prior Therapy: Participants must have fully recovered from the acute effects of prior anti-cancer therapy, and the following wash-out periods need to be observed prior to enrollment:\n* Systemic myelosuppressive therapy: ≥ 21 days after the last dose (42 days for nitrosoureas or mitomycin C).\n* Intrathecal\u002Fintraventricular chemotherapy: \\> 7 days after the last dose.\n* Small molecule\u002Ftargeted\u002Fbiologic agent: ≥ 7 days after the last dose.\n* Monoclonal antibodies: ≥ 21 days after the last dose. Other non-myelosuppressive anti-cancer agents: ≥ 3 drug half-lives after the last dose.\n* CAR-T cell therapy (systemic or intraventricular): \\> 21 days.\n\n  • Previous radiotherapy. Participants will be eligible following radiotherapy, if they meet the following criteria:\n* Previous craniospinal or total body radiotherapy: Participants must have received their last fraction ≥ 12 weeks prior to enrollment and have evidence of progressive\u002Frecurrent evaluable disease post radiation.\n* Previous focal radiotherapy to target lesions: Participants must have received their last fraction to target lesions ≥12 weeks prior to enrollment and have evidence of progressive\u002Frecurrent evaluable disease post radiation; investigators are reminded to review potentially eligible cases to avoid confusion with pseudo-progression.\n* Focal radiotherapy to non-target lesions: Participants may have received radiotherapy to nontarget lesions as long as the last fraction was \\> 14 days prior to enrollment. Participants must have at least one non-irradiated lesion that is evaluable for response.\n\n  * Performance Score: Karnofsky ≥ 50 for participants \\> 16 years of age and Lansky ≥ 50 for participants ≤ 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.\n  * Corticosteroids: Participants who are receiving corticosteroids must be on a stable or decreasing dose for at least 1 week prior to enrollment. Please also refer to arm-specific inclusion criteria for potential variations in steroid limitations.\n  * Organ Function Requirements.\n\nAdequate Bone Marrow Function Defined as:\n\n* Peripheral absolute neutrophil count (ANC) ≥ 750\u002Fmm3\n* Platelet count ≥ 75,000\u002Fcubic millimeters (mm3) (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n\nAdequate Renal Function Defined as:\n\n* Serum creatinine ≤ 1.5 Upper Limit Normal (ULN) based on age and gender\n\nAdequate Liver Function Defined as:\n\n* Total bilirubin ≤ 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) ≤ 3 x ULN\n* Aspartate aminotransferase (AST) ≤ 3 x ULN\n\nAdequate Neurologic Function Defined as:\n\n* Participants with seizure disorder may be enrolled if well controlled. See arm-specific recommendations for potential interactions between anticonvulsant agent(s) with study drug.\n\n  * Effect on the developing human fetus Recommendations on the potential effect of interventional agents on the developing human fetus will be specified in each study arm's details of therapeutic agents. Unless otherwise specified, the effects of study interventions should be considered potentially teratogenic. Thus, 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 treatment and four months after its completion. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, or should a male participant's partners become pregnant during study participation, they should inform the treating physician immediately.\n  * A legal parent\u002Fguardian or patient must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.\n  * Participants must enroll on Pediatric Neuro-oncology Consortium (PNOC) COMP if PNOC COMP is open to accrual at the enrolling institution.\n\nExclusion Criteria:\n\n* Evidence of synchronous tumors or other extra-CNS malignancy\n* Participants who are receiving any other investigational agents\n* Participants who are currently receiving other anti-cancer agents\n* Participants with uncontrolled infection or other uncontrolled systemic illness\n* Female participants of childbearing potential who are pregnant or breast-feeding. Female participants of childbearing potential must have a negative serum or urine pregnancy test prior to the start of therapy and throughout study treatment.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition as the intended treatment regimen, as detailed in that arm's treatment description.\n\nArm A\n\nInclusion Criteria:\n\n* Subjects must meet all inclusion criteria for the overall study.\n* Patients must be evaluable per Response Assessment in Pediatric Neuro-Oncology (RAPNO) criteria for medulloblastoma and other leptomeningeal seeding tumors to be evaluated for the primary endpoint (Warren et al. 2018); patients with evaluable but non-measurable disease, including leptomeningeal disease or positive CSF cytology only are eligible.\n\nPatients with recurrent or progressive ATRT who receive surgery only for their disease progression and do not have evaluable disease may be eligible for study treatment but would not be included towards the primary efficacy endpoint (to be discussed with study chairs).\n\n* Subjects must be able to swallow intact capsules.\n* Adequate Metabolic Function Defined as:\n\n  * Non-fasting glucose ≤ 140 milligrams per deciliter (mg\u002FdL) without the use of antihyperglycemic agents.\n  * If non-fasting glucose \\> 140 mg\u002FdL, a fasting glucose should be done. If fasting glucose ≤ 125 mg\u002FdL without the use of antihyperglycemic agents, participant will meet adequate metabolic function criteria.\n  * Triglycerides of \\\u003C 300 mg\u002Fdl and total cholesterol of \\\u003C 300 mg\u002Fdl - can be on lipid lowering medications as needed to achieve.\n* Adequate Cardiac Function Defined as:\n\n  * Electrocardiogram (ECG) must be obtained to verify the Corrected QT Interval (QTC). If an abnormal reading is obtained, the ECG should be repeated in triplicate.\n  * QTC \\\u003C 470 millisecond (msec)\n\nArm A\n\nExclusion Criteria:\n\nIn addition to not meeting any of the exclusion criteria of the overall study, participation on arm A will also require that subjects do not meet any of the following:\n\n* Previous exposure to gemcitabine or paxalisib\n* Concomitant use of an antihyperglycemic agent (e.g. metformin)\n* Chronic diarrhea greater than Grade 2","ALL","1 Year","39 Years",{"count":20,"type":21},29,"ESTIMATED","INTERVENTIONAL",[24],"PHASE2","This is a multi-treatment arm study that will be conducted through the Pacific Pediatric Neuro-oncology Consortium (PNOC).The study will assess the safety and efficacy of novel therapies and combinatorial strategies for participants with recurrent or progressive ATRT.",[27,28],"Recurrent Atypical Teratoid\u002FRhabdoid Tumor","Atypical Teratoid\u002FRhabdoid Tumor (ATRT) of the CNS",[30],"Novel therapies","RECRUITING","2026-06-18",{"date":34,"type":35},"2026-06-23","ACTUAL",{"date":37,"type":35},"2026-06-17",{"date":39,"type":21},"2036-12-31",{"name":41,"class":42},"Sabine Mueller, MD, PhD","OTHER",2,{"id":45,"slug":46,"hasResults":11,"nctId":47,"briefTitle":48,"officialTitle":49,"acronym":50,"eligibilityCriteria":51,"healthyVolunteers":11,"sex":16,"minAge":52,"maxAge":53,"enrollmentInfo":54,"targetDuration":4,"studyType":22,"phases":56,"briefSummary":58,"conditions":59,"keywords":68,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":70,"lastUpdatePostDateStruct":71,"startDateStruct":73,"completionDateStruct":75,"leadSponsor":77,"locationsCount":78},"100418695","phase-1-onc206-for-treatment-of-newly-diagnosed-recurrent-diffuse-midline-gliomas-and-other-recurrent-malignant-cns-tumors-100418695","NCT04732065","ONC206 for Treatment of Newly Diagnosed, Recurrent Diffuse Midline Gliomas, and Other Recurrent Malignant CNS Tumors","Open Label Phase 1 and Target Validation Study of ONC206 in Children and Young Adults With Newly Diagnosed or Recurrent Diffuse Midline Glioma (DMG), and Other Recurrent Primary Malignant Central Nervous System (CNS) Tumors","PNOC023","Inclusion Criteria:\n\n* ARM A: Children and young adults with DMG, H3K27 altered (Dose escalation: 2-21 years of age; Dose expansion: 2 years of age and above) who completed at least one line of prior therapy. Prior treatment must have included focal radiation therapy and patients must be within 4-14 weeks from completion of radiation therapy to registration (patients must start treatment within 1 week from registration), have not started any other therapies post-radiation, and have no evidence of disease progression.\n* ARM A: Tumor tissue confirmation of DMG, H3K27 altered is mandatory and pathology must be consistent with a DMG, H3K27 altered.\n* ARM A: Participants must have recovered from all acute side effects of prior therapy.\n* ARM A: From the projected start of scheduled study treatment, the following time periods must have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 4 weeks from antibodies and must be at least 7 days since the completion of therapy with a biologic or small molecule agent. For any biologic or small molecule 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 (these should be discussed with the study team)\n* ARM B: Newly diagnosed children and young adults (Dose escalation: 2-21 years of age; Dose expansion: 2 years of age and above) with a diagnosis of DMG, H3K27 altered are eligible, including spinal cord DMGs.\n* ARM B: Tumor tissue confirmation of DMG is mandatory and pathology must be consistent with a DMG, H3K27 altered.\n* ARM C: Children and young adults with DMGs (Dose escalation: 2-21 years of age; Dose expansion: 2 years of age and above) who have evidence of progression but have not been treated for this progression and are recommended to get re-irradiation.\n* ARM C: Patients must have undergone prior focal radiation therapy as part of their initial therapy and should be at least 6 months from prior radiation therapy. If timing is less than 6 months from prior focal radiation, these patients need to be discussed with the study chair(s).\n* ARM C: Tumor tissue confirmation is mandatory and pathology must be consistent with a DMG, H3K27 altered.\n* ARM C: Participants must have recovered from all acute side effects of prior therapy\n* ARM C: From the projected start of scheduled study treatment, the following time periods must have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 4 weeks from antibodies and must be at least 7 days since the completion of therapy with a biologic or small molecule agent. For any biologic or small molecule 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 (these should be discussed with the study team)\n* ARM D: Children and young adults with recurrent primary malignant CNS tumors, excluding DMGs, (Dose escalation: 2-21 years of age; Dose expansion: 2 years of age and above) who have evidence of progression but have not been treated for this progression. Participants who received a surgical resection for that progression are eligible if surgery has no curative intent. These patients need to be discussed with the study team.\n* ARM D: Prior tumor tissue confirmation is mandatory and pathology from the primary tumor must be consistent with malignant CNS tumor (diagnosis of ependymoma is allowed).Tissue at the time of progression is not required.\n* ARM D: Participants must have recovered from all acute side effects of prior therapy\n* ARM D: From the projected start of scheduled study treatment, the following time periods must have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 4 weeks from antibodies and must be at least 7 days since the completion of therapy with a biologic or small molecule agent. For any biologic or small molecule 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 (these should be discussed with the study team). Bevacizumab used for pseudoprogression does not require a wash out period.\n* TARGET VALIDATION: Newly diagnosed children and adults (2 years of age and above) with imaging consistent with a DMG, H3K27 altered are eligible.\n* TARGET VALIDATION: Children and young adults with recurrent primary malignant CNS tumors, including recurrent DMG, (2 years of age and above) who have evidence of progression but have not been treated for this progression.\n* TARGET VALIDATION: Participants must undergo tumor tissue collection as part of their standard of care\n* Participants who are receiving steroids must be on a stable or decreasing dose for at least 3 days prior to registration.\n* Peripheral absolute neutrophil count (ANC) \\>= neutrophil 1.0 g\u002Fl.\n* Platelet count \\>= 100 x 10\\^9\u002FL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n* Serum creatinine \\\u003C 1.5 Upper Limit normal (ULN) based on age and gender.\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= 3 x ULN.\n* Aspartate aminotransferase (AST) \\\u003C= 3 x ULN.\n* Patients with seizure disorder may be enrolled if seizure disorder is well controlled\n* The effects of ONC206 on the developing human fetus is unknown. For this reason, females of child-bearing potential and males must agree to use adequate contraception. Adequate methods include: hormonal or barrier method of birth control; or 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. Males treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for the duration of study participation\n* 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\n* Participants must be willing to provide adequate tissue. A minimum of 10-20 paraffin embedded unstained slides OR 1 block with tumor content of 40% or greater is required. Frozen tissue is also acceptable. Participants who previously enrolled on PNOC022 and provided adequate tissue, may not need to submit additional tissue - confirm with Study Chairs. Participants who do not meet this criterion may be discussed on a case-by-case basis with the Study Chairs.\n* 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* Patients must be enrolled on PNOC COMP if PNOC COMP is open to accrual at the enrolling institution\n\nExclusion Criteria:\n\n* Arm A \\& B: For tumors that do not have a pontine or spinal cord epicenter the following specific exclusion criteria apply: Thalamic DMG and cerebellar, H3K27 altered that has undergone standard radiation without concurrent therapy (other than temozolomide).\n* Arm C \\& D: Patients who participated in trials investigating ONC201 in the upfront setting will not be eligible. Prior ONC201 exposure as part of PNOC022 or expanded access programs will be allowed.\n* Participants who are currently receiving another investigational drug are not eligible.\n* Participants who are currently receiving other anti-cancer agents are not eligible.\n* Participants with a known disorder that affects their immune system, such as human immunodeficiency virus (HIV) or hepatitis B or C, or an auto-immune disorder requiring systemic cytotoxic or immunosuppressive therapy are not eligible. Note: Participants that are currently using inhaled, intranasal, ocular, topical or other non-oral or non-intravenous (IV) steroids are not necessarily excluded from the study but need to be discussed with the study chair.\n* Participants with uncontrolled infection.\n* Female participants of childbearing potential must not be pregnant or breast-feeding. Female participants of childbearing potential must have a negative serum or urine pregnancy test prior to the start of therapy.\n* Active illicit drug use or diagnosis of alcoholism.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC206.\n* Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant or family.\n* Any participants with illnesses that may affect absorption of ONC206.\n* Any participants on strong inhibitors or inducers of CYP3A4, 2D6, 1A2, 2C9 and 2C19 at least 14 days prior and throughout the study.","2 Years","21 Years",{"count":55,"type":21},208,[57],"PHASE1","This phase I trial studies the effects and best dose of ONC206 alone or in combination with radiation therapy in treating patients with diffuse midline gliomas that is newly diagnosed or has come back (recurrent) or other recurrent primary malignant CNS tumors. ONC206 is a recently discovered compound that may stop cancer cells from growing. This drug has been shown in laboratory experiments to kill brain tumor cells by causing a so called \"stress response\" in tumor cells. This stress response causes cancer cells to die, but without affecting normal cells. ONC206 alone or in combination with radiation therapy may be effective in treating newly diagnosed or recurrent diffuse midline gliomas and other recurrent primary malignant CNS tumors.",[60,61,62,63,64,65,66,67],"Diffuse Midline Glioma (DMG)","Glioblastoma","Recurrent Ependymoma","Recurrent Malignant Central Nervous System Neoplasm","Spinal Cord Glioma","World Health Organization (WHO) Grade III Glioma","CNS Tumor","Central Nervous System Tumor",[69],"H3 K27M-Mutant","2026-06-08",{"date":72,"type":35},"2026-06-11",{"date":74,"type":35},"2021-08-23",{"date":76,"type":21},"2027-07-31",{"name":41,"class":42},7,{"id":80,"slug":81,"hasResults":11,"nctId":82,"briefTitle":83,"officialTitle":84,"acronym":85,"eligibilityCriteria":86,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":87,"enrollmentInfo":88,"targetDuration":4,"studyType":22,"phases":90,"briefSummary":91,"conditions":92,"keywords":4,"overallStatus":96,"whyStopped":4,"lastUpdateSubmitDate":97,"lastUpdatePostDateStruct":98,"startDateStruct":100,"completionDateStruct":102,"leadSponsor":104,"locationsCount":105},"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","25 Years",{"count":89,"type":21},69,[57,24],"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.",[93,94,95],"Medulloblastoma","Medulloblastoma, Childhood","Medulloblastoma Recurrent","NOT_YET_RECRUITING","2026-05-28",{"date":99,"type":35},"2026-06-01",{"date":101,"type":21},"2026-07-30",{"date":103,"type":21},"2031-03-31",{"name":41,"class":42},1,{"id":107,"slug":108,"hasResults":11,"nctId":109,"briefTitle":110,"officialTitle":111,"acronym":112,"eligibilityCriteria":113,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":114,"targetDuration":4,"studyType":22,"phases":116,"briefSummary":117,"conditions":118,"keywords":122,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":124,"lastUpdatePostDateStruct":125,"startDateStruct":127,"completionDateStruct":129,"leadSponsor":131,"locationsCount":132},"100474997","phase-2-tovorafenib-for-treatment-of-craniopharyngioma-in-children-and-young-adults-100474997","NCT05465174","Tovorafenib for Treatment of Craniopharyngioma in Children and Young Adults","Tovorafenib for the Treatment of Newly Diagnosed or Recurrent Craniopharyngioma in Children and Young Adults","PNOC029","Inclusion Criteria:\n\nNewly Diagnosed Participants:\n\n* Newly diagnosed craniopharyngioma, as based on imaging characteristics and central radiology review. Participants will initially be screened within confines of a screening consent and only those participants with findings consistent with craniopharyngioma and without findings suggesting an indeterminate lesion or lesion of an alternative diagnosis (including abnormal tumor markers found in blood or cerebral spinal fluid (CSF), if completed as part of standard of care (SOC) work-up or if lesion concerning for alternate diagnosis) will move ahead with enrollment on the treatment protocol. Additionally, for participants that have undergone initial biopsy to confirm diagnosis, are within 6 weeks of radiographic diagnosis, and are planned to undergo follow up second surgery for additional tumor resection as per standard of care recommendations, these participants will also be considered eligible.\n* Participants must be surgical candidates for biopsy or resection and planned for standard of care biopsy or resection.\n\nRecurrent Participants:\n\n* Recurrent craniopharyngioma, as based on histologic confirmation at time of initial diagnosis (participants with Adamantinomatous craniopharyngioma (ACP) will only be eligible for the recurrent arm).\n* Recurrent craniopharyngioma without prior histologic confirmation will initially be screened within confines of a screening consent and only those participants with findings consistent with craniopharyngioma and without findings suggesting an indeterminate lesion or lesion of an alternative diagnosis (including abnormal tumor markers found in blood or CSF, if completed as part of SOC work-up or if lesion concerning for alternate diagnosis) will move ahead with enrollment on the treatment protocol.\n* Participants should be surgical candidates for biopsy or resection. If participants are not surgical candidates, but have available archival tumor tissue, they will be enrolled into the exploratory cohort.\n* Participants must be willing to provide archival tissue, a minimum of 10-20 paraffin embedded unstained slides OR 1 block with tumor content of 40% or greater is required. Participants who do not meet this criteria may be discussed on a case-by-case basis with the Study Chair(s).\n* Participants can have been previously treated with surgical resection alone, cyst drainage and biopsy alone, radiation therapy, other systemic therapies, or any combination thereof.\n* Prior Therapy:\n\n  * Had their last dose of myelosuppressive chemotherapy \\>= 21 days prior to study registration (\\>=42 days if nitrosourea therapy).\n  * Had their last dose of hematopoietic growth factor \\>=14 days (long-acting growth factor) or \\>=7 days (short-acting growth factor) prior to study registration, or beyond the time during which adverse events (AEs) are known to occur.\n  * Had their last dose of biologic (anti-neoplastic agent) \\>=7 days prior to study registration, or beyond the time during which AEs are known to occur.\n  * Had their last dose of monoclonal antibodies \\>=21 days prior to study registration.\n\nRadiation:\n\n* Had their last fraction of local irradiation to primary tumor \\>=12 weeks prior to registration; investigators are reminded to review potentially eligible cases to avoid confusion with pseudo-progression.\n* At least 14 days after local palliative radiation (small-port).\n\nAll Participants:\n\n* Age 1 to 39 years.\n* Participants continuing on maintenance therapy after standard of care biopsy\u002Fresection must have measurable disease, as defined as lesions that can be accurately measured in two dimensions (longest diameter to be recorded) with a minimum size of no less than double the slice thickness. Previously irradiated lesions are considered non-measurable except in cases of documented progression of the lesion since the completion of radiation therapy. Participants without measurable disease may continue on study and will be followed for study endpoints, but will not be included as part of target accrual.\n* Performance Score: 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.\n* Corticosteroids: Participants who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to registration. The participant steroid dose should be no more than a steroid-equivalent of dexamethasone 0.1 mg\u002Fkg\u002Fday (or maximum 4mg\u002Fday; whichever is the lower dose) at time of enrollment. Participants that have been stable on physiologic hormone replacement for hypopituitarism are allowed.\n* Organ Function Requirements:\n\n  * Adequate Bone Marrow Function defined as:\n\n    * Peripheral absolute neutrophil count (ANC) \\>=1000\u002Fmm3.\n    * Platelet count \\>= 100,000\u002Fmm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n  * Adequate Renal Function defined as-\n\n    ---A serum creatinine \\\u003C 1.5 Upper Limit normal (ULN) based on age and gender.\n  * Adequate Liver Function defined as-\n\n    * Bilirubin (sum of conjugated + unconjugated) \\\u003C= 1.5 x upper limit of normal (ULN) for age (except in participants with documented Gilbert syndrome).\n    * Serum glutamic-pyruvic transaminase (SGPT)((alanine aminotransferase (ALT)) \\\u003C= 3 x ULN.\n    * Serum albumin \\>=2 g\u002FdL (20g\u002FL).\n  * Adequate Neurologic Function defined as 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.\n  * Adequate Pulmonary Function defined as no evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry of \\> 92% while breathing room air.\n  * prothrombin time (PT) \u002Fpartial thromboplastin time (PTT)\u002FInternational Normalized Ratio (INR) within institutional normal limits or deemed appropriate for surgical intervention by the treating team for patients undergoing surgery biopsy\u002Fresection\n* The effects of Tovorafenib on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (non-hormonal contraception; barrier method of birth control; abstinence - note, tovorafenib can make hormonal contraceptives ineffective) prior to study entry, for the duration of study participation and 28 days after completion of Tovorafenib administration, whichever is later. 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* A legal parent\u002Fguardian or participants must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.\n* Ability to complete the PedsQL Core Module.\n* Patients must enroll on PNOC COMP if PNOC COMP is open to accrual at the enrolling institution.\n\nExclusion Criteria:\n\nNewly Diagnosed Participants:\n\n\\- Participants should not have undergone any previous tumor-directed therapy.\n\nRecurrent Participants:\n\n* 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 acute adverse events due to agents administered more than 4 weeks earlier.\n* Participants must be at least 1 week since the completion of therapy with a biologic or small molecule agent. For any agent with known adverse events that can occur beyond 1 week 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.\n* Participants should not have previously received any RAS-pathway, but have not received Tovorafenib will be eligible.\n\nAll Participants:\n\n* Rapidly progressive symptoms that require urgent surgery or radiation therapy, which would prevent central review and or preclude participation with tumor-directed medical management alone.\n* Uncontrolled symptoms of neuroendocrine dysfunction such as diabetes insipidus, hypothyroidism, panhypopituitarism (participants can be on supplemental medications for hormonal repletion; however, should be on controlled doses for at least 2 weeks prior to enrollment).\n* Clinically significant active cardiovascular disease, or history of myocardial infarction, or deep vein thrombosis\u002Fpulmonary embolism within 6 months prior to registration, ongoing cardiomyopathy, or current prolonged QT interval corrected for heart rate by Fridericia's formula (QTcF) interval \\> 440 ms based on triplicate ECG average.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to tovorafenib.\n* Nausea and vomiting \\>= Grade 2, malabsorption requiring supplementation, or significant bowel or stomach resection that would preclude adequate absorption.\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection.\n* Participants who are receiving any other investigational agents.\n* Women of childbearing potential must not be pregnant or breast-feeding.\n* Current treatment with a strong cytochrome P4502C8(CYP2C8) inhibitor or inducer other than those allowed per Section 5.6.1. Medications that are substrates of CYP2C8 are allowed but should be used with caution.\n* Participants with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.",{"count":115,"type":21},57,[24],"The current study assesses the tolerability and efficacy of monotherapy with pan-RAF-kinase (Tovorafenib) inhibition for the treatment of children and young adults with craniopharyngioma.",[119,120,121],"Craniopharyngioma, Child","Craniopharyngioma","Recurrent Craniopharyngioma",[123],"Neoadjuvant therapy","2026-04-21",{"date":126,"type":35},"2026-04-23",{"date":128,"type":35},"2022-09-12",{"date":130,"type":21},"2028-03-01",{"name":41,"class":42},20,{"id":134,"slug":135,"hasResults":11,"nctId":136,"briefTitle":137,"officialTitle":138,"acronym":4,"eligibilityCriteria":139,"healthyVolunteers":11,"sex":16,"minAge":140,"maxAge":18,"enrollmentInfo":141,"targetDuration":4,"studyType":22,"phases":143,"briefSummary":144,"conditions":145,"keywords":4,"overallStatus":96,"whyStopped":4,"lastUpdateSubmitDate":150,"lastUpdatePostDateStruct":151,"startDateStruct":153,"completionDateStruct":155,"leadSponsor":157,"locationsCount":105},"100622873","phase-1-combination-adi-peg-20-tmz-and-rt-for-treatment-of-newly-diagnosed-high-grade-glioma-hgg-100622873","NCT07389278","Combination ADI-PEG 20, TMZ, and RT for Treatment of Newly Diagnosed High-grade Glioma (HGG)","A Phase 1\u002F2 Study of Pegylated Arginine Deiminase (ADI-PEG 20) Plus Radiotherapy (RT) and Temozolomide (TMZ) in Children, Adolescents, and Young Adults With Newly Diagnosed High-grade Glioma (HGG)","Inclusion Criteria:\n\n1. Participants must have histologically and molecularly confirmed newly diagnosed World Health Organization (WHO) grade 3 or 4 glioma.\n\n   1. Phase 1: any newly diagnosed HGG (including DMG of any location and primary spinal cord tumors).\n   2. Phase 2:\n\n      * Cohort 1: Newly diagnosed non-pontine, non-spinal cord HGG histone-wildtype.\n      * Cohort 2: Newly diagnosed non-pontine, non-spinal cord H3K27 altered diffuse midline glioma (DMG).\n      * Cohort 3: Newly diagnosed non-pontine, non-spinal cord H3G34 mutant diffuse hemispheric glioma (DHG).\n2. Prior surgery: must have undergone maximal safe resection. For patients with DMG of the pons, biopsy is sufficient.\n3. Prior Therapy: Participants must NOT have received ANY prior therapy (except surgery) before enrollment on study.\n4. Tumor Tissue Requirement: Participants must have sufficient tumor tissue (5-10 unstained formalin-fixed paraffin-embedded (FFPE) slides or a tumor block) for study enrollment.\n5. Age:\n\n   Phase 1:\n\n   o 3 to \\\u003C18 years of age.\n\n   Phase 2:\n   * Cohort 1: 3 to 25 years of age.\n   * Cohorts 2 \\& 3: 3 to 39 years of age.\n6. Performance Score: 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.\n7. Corticosteroids: Participants who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to registration.\n8. Organ Function Requirements:\n\n   1. Peripheral absolute neutrophil count (ANC) \\>= 1000\u002Fmm\\^3.\n   2. Platelet count \\>= 100,000\u002Fmm\\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n   3. Creatinine Clearance (CrCl) or estimated glomerular filtration rate (eGFR) with cutoff value of ≥ 60 mL\u002Fmin for renal function in participants with age ≥ 18 years. For participants \\\u003C 18 years old, estimate eGFR using the Schwartz equation. eGFR (mL\u002Fmin\u002F1.73 m\\^2) = (k × Height (cm)) \u002F Serum Creatinine (mg\u002FdL).\n   4. 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   5. alanine aminotransferase (ALT) \\\u003C= 3 x ULN.\n   6. aspartate aminotransferase (AST) \\\u003C= 3 x ULN.\n   7. 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.\n9. The effects of ADI-PEG 20 have been shown to be associated with embryofetal toxicity in rodents. For this reason and because chemotherapy 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 treatment. 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.\n10. A legal parent\u002Fguardian or participant must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.\n11. Participants must enroll on PNOC COMP if PNOC COMP is open to accrual at the enrolling institution.\n\nExclusion Criteria:\n\n1. Participants who have received any systemic therapy or RT, including any investigational agents.\n2. History of allergic reactions attributed to compounds of similar chemical or biologic composition to ADI-PEG 20 such as pegylated compounds.\n3. Phase 2 cohorts: tumors with epicenter in pons or spinal cord\n4. Participants with metastatic or leptomeningeal disease. Multi-focal disease should be discussed with the study chairs,\n5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection that would interfere with the study.\n6. Women of childbearing potential must not be pregnant or breast-feeding.\n7. 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.\n8. Corrected QT Interval (QTc) cutoff \\>480 ms.\n\nImportant note: The eligibility criteria listed above are interpreted literally and cannot be waived.","3 Years",{"count":142,"type":21},97,[57,24],"This is an open label, intra-patient dose escalation, to evaluate ADI-PEG 20, in combination with Temozolomide (TMZ) and radiation therapy (RT) in children, adolescents and young adult patients with newly diagnosed high grade glioma (HGG).",[61,146,147,148,149],"High-Grade Glioma (WHO III-IV)","High-grade Glioma","Diffuse Midline Glioma, H3 K27M-Mutant","Diffuse Hemispheric Glioma, H3G34 Mutant","2026-01-28",{"date":152,"type":35},"2026-02-05",{"date":154,"type":21},"2026-03-09",{"date":156,"type":21},"2035-06-30",{"name":41,"class":42},""]