[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"recurrent-diffuse-intrinsic-pontine-glioma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:recurrent-diffuse-intrinsic-pontine-glioma":30},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,3,0,[8,47,82],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":20,"targetDuration":4,"studyType":23,"phases":24,"briefSummary":26,"conditions":27,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":35,"lastUpdatePostDateStruct":36,"startDateStruct":39,"completionDateStruct":41,"leadSponsor":43,"locationsCount":46},"100440030","phase-2-combination-therapy-for-the-treatment-of-diffuse-midline-gliomas-100440030",false,"NCT05009992","Combination Therapy for the Treatment of Diffuse Midline Gliomas","A Combination Therapy Trial Using an Adaptive Platform Design for Children and Young Adults With Diffuse Midline Gliomas (DMGs) Including Diffuse Intrinsic Pontine Gliomas (DIPGs) at Initial Diagnosis, Post-Radiation Therapy and at Time of Progression","PNOC022","--COHORTS 1, 2, AND 3 CLOSED---\n\nINCLUSION CRITERIA:\n\nCOHORT 1A AND 1B:\n\n* New diagnosis of DMG with imaging and\u002For pathology consistent with a DMG, including spinal cord tumors. In cohort 1B, previous tumor tissue confirmation of DMG is mandatory and pathology must be consistent with a DMG including diffuse midline glioma Histone 3 lysine 27 - mutant (H3K27M); World Health Organization (WHO) grade III and IV H3 wildtype gliomas.\n* Must be within 6 weeks of diagnosis to begin standard of care radiation therapy on study.\n\nCOHORT 2A AND 2B:\n\n* Diagnosis of DMG with imaging and\u002For pathology consistent with a DMG, including spinal cord tumors, who have complete standard-of-care radiation therapy. In Cohort 2B, previous tumor tissue confirmation of DMG is mandatory and pathology must be consistent with a DMG including diffuse midline glioma H3K27M mutant; WHO grade III and IV H3 wildtype gliomas.\n* Participants must be within 4-14 weeks of completion of radiation. Radiation should have started within 6 weeks of diagnosis.\n\nCOHORT 3A AND 3B:\n\n* Diagnosis of recurrent DMG with imaging and\u002For pathology consistent with a DMG, including spinal cord tumors, who have complete standard-of-care radiation therapy. In cohort 3B, previous tumor tissue confirmation of DMG is mandatory and pathology must be consistent with a DMG including diffuse midline glioma H3K27M mutant; WHO grade III and IV H3 wildtype gliomas.\n* Participants must have evidence of progression and not have received any treatment for this progression and have not previously received re-irradiation.\n\nCOHORT 4A AND 4B:\n\n* Diagnosis of DMG with imaging and\u002For pathology consistent with a DMG, including spinal cord tumors. In cohort 4B\\^1, previous tumor tissue confirmation of DMG is mandatory and pathology must be consistent with a DMG diffuse midline glioma H3K27-altered.\n* Not currently eligible for any other clinical trials that include administration of ONC201.\n\nCohort 4A\\^1 and 4B\\^1 (participants with newly diagnosed DMG prior to radiation): Must be able to begin standard of care radiation therapy on study within 6 weeks of diagnosis.\n\nCohort 4A\\^2 and 4B\\^2 (participants with newly diagnosed DMG who have completed radiation): Participants must be within 4-14 weeks of completion of radiation and not have received additional therapy beyond completion of radiation therapy. Radiation should have started within 6 weeks of diagnosis.\n\nCohort 4A\\^3 and 4B\\^3 (participants with DMG at progression): Participants must have evidence of progression and not have received any treatment for this progression and have not previously received re-irradiation.\n\nCOHORT 5\n\n* Diagnosis of DMG with imaging and\u002For pathology consistent with a DMG, including spinal cord tumors. In cohort 5\\^1, previous tumor tissue confirmation of DMG is mandatory and pathology must be consistent with a DMG diffuse midline glioma H3K27-altered.\n* Not currently eligible for any other clinical trials that include administration of ONC201.\n* Multifocal and leptomeningeal disease will be eligible for Cohort 5.\n* Participant's tumor must demonstrate one of the following molecular alterations considered targetable by an approved agent:\n\n  * BRAFV600E\n  * PDGFRA (DNA point mutation or amplification with \\>=5 copy numbers)\n  * FGFR1 (DNA point mutation, gene fusions, or amplification with \\>=5 copy numbers)\n  * NF1\n\nCohort 5\\^1 (participants pre-radiation): Must be able to begin standard of care radiation therapy on study within 6 weeks of diagnosis.\n\nCohort 5\\^2 (participants post-radiation): Participants must be within 4-14 weeks of completion of radiation and not have received additional therapy beyond completion of radiation therapy. Radiation should have started within 6 weeks of diagnosis.\n\nCohort 5\\^3 (participants with progression): Participants must have evidence of progression and not have received any treatment for this progression and have not previously received re-irradiation.\n\nAll Cohorts (except Cohort 6):\n\n* Age 2 to 39 years\n* Participants must have recovered from all acute side effects of prior therapy and be beyond the window for expected ongoing acute toxicities. Any number of prior therapies are allowed.\n* Prior ONC201 exposure is allowed, except in participants who have participated in Chimerix trials investigating ONC201 in the upfront setting. Participants who participated in trials investigating ONC201 in the upfront setting will not be eligible at any time, with the exception if participants received ONC201 as part of PNOC022 or other expanded access programs such as German sources of ONC201.\n* Participant body weight must be above the minimum necessary for the participant to receive ONC201 (at least 10 kilograms (kg))\n* From the projected start of scheduled study treatment, the following time periods must have elapsed: At least 7 days after last dose of a biologic agent or beyond time during which adverse events are known to occur for a biologic agent, 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from antibodies (21 days for bevacizumab when used for tumor-directed therapy, guidance on use for pseudo-progression is below), or, or 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies.\n\n  o The use of bevacizumab to control radiation therapy-induced edema is allowed (if used for tumor-directed therapy, please see required time period above).\n  * Dosing limitations are as follows:\n  * \\* Bevacizumab (or equivalent) for up to a maximum of 5 doses, dosing per institutional standard. There is no required washout period.\n* Prior use of temozolomide during radiation at maximum of the standard pediatric dosing (defined as 90 mg\u002Fm2 \u002Fdose continuously during radiation therapy for 42 days) or dexamethasone is allowed. Any other agent given throughout radiation therapy must be discussed with the study chairs prior to beginning the agent.\n* Corticosteroids: Participants who are receiving dexamethasone must be on a stable or decreasing dose for at least 3 days prior to baseline magnetic resonance imaging (MRI) scan.\n* The participant must have adequate organ function defined as:\n\n  * Peripheral absolute neutrophil count (ANC) \\>= 750\u002Fmm\\^3 (1.0g\u002Fl) AND\n  * Platelet count \\>= 75,000\u002Fmm\\^3 (100x10\\^9\u002Fl) (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n  * Creatinine clearance or radioisotope glomerular filtration rate (GFR) \\>= 70 mL\u002Fmin\u002F1.73 m\\^2 OR\n  * A serum creatinine within the normal limits for age\n  * Bilirubin (sum of conjugated + unconjugated) =\\\u003C 1.5 x upper limit of normal (ULN) for age AND\n  * Serum glutamate pyruvate transaminase (SGPT)(alanine aminotransferase (ALT)) =\\\u003C 3 x ULN AND\n  * Serum albumin \\>= 2 g\u002FDl\n  * No evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry of \\> 92% while breathing room air.\n  * Diarrhea \\\u003C grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0\n  * No history of congestive heart failure or family history of long QT syndrome.\n  * ECG must be obtained to verify the Corrected QT Interval (QTc). If an abnormal reading is obtained, the ECG should be repeated in triplicate. QTC \\\u003C 470 msec.\n  * Participants with history of congestive heart failure, at risk of having or have underlying cardiovascular disease, or with history of exposure to cardiotoxic drugs must have adequate cardiac function as determined by echocardiogram. Shortening fraction of \\>= 27%.\n  * Participants with seizure disorder may be enrolled if seizure disorder is well controlled\n* Females of child-bearing potential and males must agree to use adequate contraception.\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.\n\nCOHORT 6 Inclusion Criteria:\n\n* Diagnosis of newly diagnosed thalamic or pontine located DMG with imaging and\u002For pathology consistent with a DMG, excluding spinal cord tumors, who have completed standard-of-care radiation therapy. If archival tissue is available prior to first biopsy, 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.\n* Participants must be within 4-14 weeks of completion of radiation. Radiation should have started within 6 weeks of diagnosis.\n* Age 2-39 years.\n* Prior use of temozolomide during radiation at maximum of the standard pediatric dosing (defined as 90 mg\u002Fm2 \u002Fdose continuously during radiation therapy for 42 days) is allowed. Any other agent given throughout radiation therapy must be discussed with the study chairs prior to enrollment.\n* Participants must have recovered from all acute side effects of prior therapy and be beyond the window for expected ongoing acute toxicities. Washout requirements from prior therapy include:\n\n  * At least 7 days after last dose of a biologic agent or beyond time during which adverse events are known to occur for a biologic agent, 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 30 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from antibodies (28 days for bevacizumab when used for tumor-directed therapy, guidance on use for pseudo-progression is below), or 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies.\n  * At least 4 weeks prior to study enrollment from last immune therapy\n* Corticosteroids: Participants treated with corticosteroids must be on stable or decreasing dose for at least 1 week prior to enrollment, with maximum dexamethasone dose 0.1 mg\u002Fkg\u002Fday dexamethasone equivalent at time of enrollment.\n* The participant must have adequate organ function defined as:\n\n  * Peripheral absolute neutrophil count (ANC) \\>= 750\u002Fmm3 (1.0g\u002Fl) and\n  * Platelet count \\>= 75,000\u002Fmm3 (100x109\u002Fl) (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment.\n  * Creatinine clearance or radioisotope GFR \\>= 70mL\u002Fmin\u002F1.73 m2 or\n  * A serum creatinine within the normal limits for age.\n  * Total bilirubin \\\u003C= 3 x upper limit of normal (ULN); in presence of Gilbert's syndrome, total bilirubin \\\u003C\u002F= 6 x ULN or direct bilirubin \\\u003C= 3 x ULN\n  * ALT \\\u003C= 5 x ULN\n  * AST \\\u003C= 5 x ULN.\n  * Serum albumin \\>= 2 g\u002FdL\n  * Diarrhea \\\u003C grade 2 by CTCAE v5.0.\n  * No history of congestive heart failure or family history of long QT syndrome.\n  * Participants with seizure disorder may be enrolled if seizure disorder is well controlled.\n* The effects of the study drugs on the developing human fetus are unknown. For this reason, females of child-bearing potential and males must agree to use adequate contraception.\n* Karnofsky \\>\u002F= 70 for Participants \\> 16 years of age and Lansky \\>\u002F= 70 for participants \\\u003C\u002F= 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\nEXCLUSION CRITERIA:\n\nCOHORT 1A AND 1B:\n\n* Prior exposure to radiation therapy.\n* Thalamic and Cerebellar H3K27M DMG.\n\nCOHORT 2A AND 2B:\n\n* For tumors that do not have a pontine or spinal cord epicenter the following specific exclusion criteria apply:\n* Thalamic and Cerebellar H3K27M DMG that has undergone standard radiation without concurrent therapy (other than temozolomide).\n\nCOHORT 1A AND 2A:\n\n• Deemed not appropriate for tissue resection\u002Fbiopsy.\n\nCOHORT 3A AND 3B:\n\n* Prior exposure to re-irradiation for tumor progression.\n* Thalamic and cerebellar H3K27M mutant DMG.\n\nCOHORT 4A AND 4B:\n\nCohort 4A\\^1and 4B\\^1: Prior exposure to radiation therapy Cohort 4A\\^3 and 4B\\^3: Prior exposure to re-irradiation for tumor progression\n\n* Thalamic and cerebellar H3K27M mutant DMG, except those who received ONC201\u002FONC026 from alternative source prior to 2024 or US patients enrolled while the accelerated approval new drug application for dordaviprone to treat recurrent H3 K27M-mutant diffuse glioma is under review by US FDA.\n* Cohort 4A\\^1and 4B\\^1: Prior exposure to radiation therapy\n* Cohort 4A\\^3 and 4B\\^3: Prior exposure to re-irradiation for tumor progression\n\nCOHORT 5:\n\n* Thalamic and cerebellar H3K27M mutant DMG, except those who received ONC201\u002FONC026 from alternative source prior to 2024 or US patients enrolled while the accelerated approval new drug application for dordaviprone to treat recurrent H3 K27M-mutant diffuse glioma is under review by US FDA.\n* Cohort 5\\^1: Prior exposure to radiation therapy\n* Cohort 5\\^3: Prior exposure to re-irradiation for tumor progression\n\nAll Cohorts (except Cohort 6):\n\n* Diagnosis of a histone H3 wildtype grade II diffuse astrocytoma.\n* Participants who are currently receiving another investigational drug. Investigational imaging agents or agents used to enhance tumor visibility on imaging or during tumor biopsy\u002Fresection should be discussed with the study chairs.\n* Participants who are currently receiving other anti-cancer agents.\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. 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 or other uncontrolled systemic illness.\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 (as clinically indicated).\n* Active illicit drug use or diagnosis of alcoholism.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition as the agents used in study.\n* Evidence of disseminated disease, including diffuse leptomeningeal disease or evidence of CSF dissemination, with the exception of Cohort 5.\n* Known additional malignancy that is progressing or requires active treatment within 3 years of start of study drug.\n* Concomitant use of potent CYP3A4\u002F5 inhibitors during the treatment phase of the study and within 72 hours prior to starting study drug administration.\n* Concomitant use of potent CYP3A4\u002F5 inducers, which include enzyme inducing antiepileptic drugs (EIAEDs), during the treatment phase of the study and within 2 weeks prior to starting treatment. Concurrent corticosteroids is allowed.\n\nCOHORT 6 Exclusion Criteria:\n\n* • DMGs located outside the thalamus and pons including bilateral thalamic tumors.\n* Unacceptable anesthesia or surgery risk, as determined by the anesthesiologist or the neurosurgeon.\n* Evidence of significant mass effect\n* Evidence of herniation on imaging.\n* Participants with a known history coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of registration.\n* Participants must not require systemic anti-coagulation that cannot be halted for each intraoperative and perioperative biopsy time-period.\n* Participants with active viral infection or who are currently receiving antiviral treatment.\n* Participants with active, known, or suspected immunosuppressive disorders, such as acquired or congenital immune deficiency syndromes and autoimmune diseases.\n* This virus infects cells with a deficit in the RB gene. Therefore, participants with Li-Fraumeni Syndrome or a known germ line deficit in the retinoblastoma gene or its related pathway are excluded.\n* Participants must not have live or live-attenuated vaccinations within 30 days prior to DNX-2401 administration and while participating in the study. Killed vaccines are permitted.\n* Participants who are currently receiving another investigational drug. Investigational imaging agents or agents used to enhance tumor visibility on imaging or during tumor biopsy\u002Fresection should be discussed with the study chairs.\n* Participants with a known disorder that affects their immune system, such as HIV or Hepatitis B or C, or an auto-immune disorder requiring systemic cytotoxic or immunosuppressive therapy. Note: Participants who are currently using inhaled, intranasal, ocular, topical or other non-oral or non-IV steroids are not necessarily excluded from the study but need to be discussed with the study chair(s).\n* Participants with uncontrolled infection or other uncontrolled systemic illness.\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 (as clinically indicated).\n* Active illicit drug use or diagnosis of alcoholism.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition as the agents used in the study.\n* Evidence of disseminated disease, including multi-focal disease, diffuse leptomeningeal disease or CSF dissemination.","ALL","2 Years","39 Years",{"count":21,"type":22},360,"ESTIMATED","INTERVENTIONAL",[25],"PHASE2","This phase II trial determines if the combination of ONC201 with different drugs is effective for treating participants with diffuse midline gliomas (DMGs). Despite years of research, little to no progress has been made to improve outcomes for participants with DMGs, and there are few treatment options. This trial will utilize an adaptive platform design in that the different treatment arms for each cohort will be opened and closed based on ongoing preclinical investigation as well as evolving outcome data from the trial.\n\nNovel agents will be continuously added to this study as pre-clinical data emerge to suggest additive or synergistic activity when combined ONC201. Should a novel agent not have an RP2D at the time of incorporation into this study, a phase 1 lead-in will be performed prior to initiation of combination therapy (via study amendment).",[28,29,30,31,32,33],"Diffuse Intrinsic Pontine Glioma","Diffuse Midline Glioma, H3 K27M-Mutant","Recurrent Diffuse Intrinsic Pontine Glioma","Recurrent Diffuse Midline Glioma, H3 K27M-Mutant","Recurrent WHO Grade III Glioma","WHO Grade III Glioma","RECRUITING","2026-06-23",{"date":37,"type":38},"2026-06-26","ACTUAL",{"date":40,"type":38},"2021-10-20",{"date":42,"type":22},"2029-06-30",{"name":44,"class":45},"University of California, San Francisco","OTHER",32,{"id":48,"slug":49,"hasResults":11,"nctId":50,"briefTitle":51,"officialTitle":52,"acronym":4,"eligibilityCriteria":53,"healthyVolunteers":11,"sex":17,"minAge":54,"maxAge":55,"enrollmentInfo":56,"targetDuration":4,"studyType":23,"phases":58,"briefSummary":60,"conditions":61,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":71,"lastUpdatePostDateStruct":72,"startDateStruct":74,"completionDateStruct":76,"leadSponsor":78,"locationsCount":81},"100429351","phase-1-cbl0137-for-the-treatment-of-relapsed-or-refractory-solid-tumors-including-cns-tumors-and-lymphoma-100429351","NCT04870944","CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma","A Phase 1\u002F2 Trial of CBL0137 (NSC# 825802) in Patients With Relapsed or Refractory Solid Tumors Including CNS Tumors and Lymphoma","Inclusion Criteria:\n\n* Parts A and B: Patients must be \\>= 12 months and =\\\u003C 21 years of age at the time of study enrollment\n* Patients must have had histologic verification of malignancy at original diagnosis or relapse, except in patients with diffuse intrinsic brain stem tumors, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers, including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)\n\n  * Part A: Patients with relapsed or refractory solid tumors or lymphoma, including patients with CNS tumors or known CNS metastases (including untreated or progressive) are eligible\n  * Part B: Patients with progressive or recurrent DIPG (diagnosed by biopsy or imaging characteristics) and other H3 K27-altered DMG previously treated with radiation therapy\n* Part A: Patients must have either measurable or evaluable disease\n* Part B: Patients must have measurable disease\n* Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life\n* Patients must have a performance status corresponding to Easter Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \\> 16 years of age and Lansky for patients =\\\u003C 16 years of age. Patients must have a Karnofsky or Lansky score \\>= 50%\n* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately\n\n  * Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive\n\n    * Solid tumor patients: \\>= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)\n  * Anti-cancer agents not known to be myelosuppressive (eg, not associated with reduced platelet or absolute neutrophil count \\[ANC\\] counts): \\>= 7 days after the last dose of agent\n  * Antibodies: \\>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\\\u003C 1\n  * Corticosteroids: If used to modify immune adverse events related to prior therapy, \\>= 14 days must have elapsed since last dose of corticosteroid. Patients with CNS tumors receiving corticosteroids must have been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment\n  * Hematopoietic growth factors: \\>= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur\n  * Interleukins, interferons and cytokines (other than hematopoietic growth factors): \\>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)\n  * Stem cell Infusions (with or without total body irradiation \\[TBI\\]):\n\n    * Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: \\>= 84 days after infusion and no evidence of graft versus host disease (GVHD)\n    * Autologous stem cell infusion including boost infusion: \\>= 30 days\n  * Cellular therapy: \\>= 42 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer \\[NK\\] cells, dendritic cells, etc.)\n  * Radiation therapy \\[XRT\\]\u002Fexternal beam irradiation including protons: \\>= 14 days after local XRT; \\>= 150 days after TBI, craniospinal XRT or if radiation to \\>= 50% of the pelvis; \\>= 42 days if other substantial bone marrow (BM) radiation\n  * Radiopharmaceutical therapy (e.g., radiolabeled antibody, I-131 metaiodobenzylguanidine \\[131I MIBG\\]): \\>= 42 days after systemically administered radiopharmaceutical therapy\n  * Patients must not have received prior exposure to CBL0137\n* For patients with solid tumors without known bone marrow involvement:\n\n  * Peripheral absolute neutrophil count (ANC) \\>= 1000\u002FuL (performed within 7 days prior to enrollment unless otherwise indicated)\n  * Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity\n* For patients with solid tumors without known bone marrow involvement:\n\n  * Platelet count \\>= 100,000\u002FuL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (performed within 7 days prior to enrollment unless otherwise indicated)\n  * Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity\n* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \\>= 70 mL\u002Fmin\u002F1.73 m\\^2 or a creatinine based on age\u002Fsex as follows (performed within 7 days prior to enrollment unless otherwise indicated):\n\n  * Age: Maximum serum creatinine (mg\u002FdL)\n  * 1 to \\\u003C 2 years: 0.6 (male); 0.6 (female)\n  * 2 to \\\u003C 6 years: 0.8 (male); 0.8 (female)\n  * 6 to \\\u003C 10 years: 1 (male); 1 (female)\n  * 10 to \\\u003C 13 years: 1.2 (male); 1.2 (female)\n  * 13 to \\\u003C 16 years: 1.5 (male); 1.4 (female)\n  * \\>= 16 years: 1.7 (male); 1.4 (female)\n* Patients with solid tumors:\n\n  * Bilirubin (sum of conjugated + unconjugated or total) =\\\u003C 1.5 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment unless otherwise indicated)\n* Patients with solid tumors:\n\n  * Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \\[ALT\\]) =\\\u003C 135 U\u002FL. For the purpose of this study, the ULN for SGPT is 45 U\u002FL (performed within 7 days prior to enrollment unless otherwise indicated)\n* Shortening fraction of \\>= 27% by echocardiogram (performed within 7 days prior to enrollment unless otherwise indicated) or\n* Ejection fraction of \\>= 50% by gated radionuclide study (performed within 7 days prior to enrollment unless otherwise indicated)\n* Corrected QT (QTC) \\\u003C 480 msec (performed within 7 days prior to enrollment unless otherwise indicated)\n* Patients with seizure disorder may be enrolled if seizures well controlled without the use of enzyme-inducing anti-convulsant agents. Well controlled is defined by no increase in seizure frequency in the prior 7 days\n* Nervous system disorders (Common Terminology Criteria for Adverse Events \\[CTCAE\\] version \\[v\\]5) resulting from prior therapy must be =\\\u003C grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible\n* Patients have consented to receive a central venous catheter prior to the administration of CBL0137. A central line is required for CBL0137 administration\n\nExclusion Criteria:\n\n* Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal\u002Fhuman studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control\n* Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, \\>= 14 days must have elapsed since last dose of corticosteroid\n* Patients who are currently receiving another investigational drug are not eligible\n* Patients who are currently receiving other anti-cancer agents are not eligible (except leukemia patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy)\n* Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial\n* Patients who are receiving drugs that are strong inducers or inhibitors of CYP3A4, CYP2B6 (e.g., carbamazepine) and CYP1A2 (e.g., ciprofloxacin, enoxacin, fluvoxamine, smoking) are not eligible. These agents are to be avoided for 7 days prior to the start of CBL0137 and for the duration of the protocol therapy. Sensitive substrates of CYP2D6 (e.g., atomoxetine, desipramine, dextromethorphan, eliglustat, nebivolol, nortriptyline, perphenazine, tolterodine, R-venlafaxine) should also be avoided for the duration protocol therapy\n* Patients who are receiving drugs associated with a known risk of Torsades de Pointes (TdP) are not eligible. Drugs associated with known risk of Torsades de Pointes (TdP) are to be avoided for 7 days prior to the start of CBL0137 and for duration of the protocol therapy\n* Patients with known peripheral vascular disease are excluded\n* Patients with a history of pro-thrombotic disorder are not eligible\n* Patients who have an uncontrolled infection are not eligible\n* Patients who have received a prior solid organ transplantation are not eligible\n* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible","12 Months","21 Years",{"count":57,"type":22},63,[59,25],"PHASE1","This phase I\u002FII trial evaluates the best dose, side effects and possible benefit of CBL0137 in treating patients with solid tumors, including central nervous system (CNS) tumors or lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Drugs, such as CBL0137, block signals passed from one molecule to another inside a cell. Blocking these signals can affect many functions of the cell, including cell division and cell death, and may kill cancer cells.",[62,63,30,64,65,66,67,68,69,70],"Diffuse Midline Glioma, H3 K27-Altered","Metastatic Malignant Neoplasm in the Central Nervous System","Recurrent Diffuse Midline Glioma, H3 K27-Altered","Recurrent Lymphoma","Recurrent Malignant Solid Neoplasm","Recurrent Primary Malignant Central Nervous System Neoplasm","Refractory Lymphoma","Refractory Malignant Solid Neoplasm","Refractory Primary Malignant Central Nervous System Neoplasm","2026-05-01",{"date":73,"type":38},"2026-05-05",{"date":75,"type":38},"2022-01-28",{"date":77,"type":22},"2026-12-31",{"name":79,"class":80},"Children's Oncology Group","NETWORK",35,{"id":83,"slug":84,"hasResults":11,"nctId":85,"briefTitle":86,"officialTitle":87,"acronym":4,"eligibilityCriteria":88,"healthyVolunteers":11,"sex":17,"minAge":89,"maxAge":19,"enrollmentInfo":90,"targetDuration":4,"studyType":23,"phases":92,"briefSummary":93,"conditions":94,"keywords":107,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":111,"lastUpdatePostDateStruct":112,"startDateStruct":114,"completionDateStruct":116,"leadSponsor":118,"locationsCount":120},"100460636","phase-1-lutathera-for-treatment-of-recurrent-or-progressive-high-grade-cns-tumors-100460636","NCT05278208","Lutathera for Treatment of Recurrent or Progressive High-Grade CNS Tumors","Phase I\u002FII Study of Lutathera in Patients With Recurrent and\u002For Progressive High-Grade Central Nervous System Tumors and Meningiomas That Demonstrate Uptake on DOTATATE PET","All participants must meet the following inclusion and exclusion criteria. No exceptions will be given. Imaging studies to establish eligibility must be done within three weeks prior to enrollment. All other clinical evaluations to establish eligibility (except for \\[68Ga\\]Ga-DOTATATE PET) must be done within 7 days prior to enrollment.\n\n1. Screening Criteria\n\n   1.1 Diagnosis Patient must have a diagnosis of primary high-grade CNS tumor (any histopathologic diagnosis that is WHO grade III-IV) or meningioma (any histologic grade) that is recurrent, progressive, or refractory. Note that patients with DIPG (based on radiographic\u002Fclinical diagnosis) who have undergone biopsy will be eligible with histologic diagnosis of grade II-IV infiltrating glioma. All tumors must have histologic verification either at the time of diagnosis or recurrence, except for patients meningioma who have not previously undergone biopsy or resection.\n\n   Note: Refractory disease is defined as the presence of persistent abnormality on conventional MRI that is further distinguished by histology (biopsy or sample of lesion) or advanced imaging, OR as determined by the treating physician and discussed with the primary investigator prior to enrollment.\n\n   1.2 Prior Therapy Patients must have recurred\u002Fprogressed following prior standard therapy for their tumor. Note: Patients with meningioma, atypical meningioma, or anaplastic meningioma must have received at least surgical resection or radiation.\n\n   1.3 Screening Consent Participant\u002Flegal guardian is willing to sign a screening consent for \\[68Ga\\]Ga-DOTATATE PET imaging. The screening consent is to be obtained according to institutional guidelines. Assent, when appropriate, will be obtained according to institutional guidelines.\n2. Eligibility Criteria\n\n   * Phase I Age Patient must be ≥ 4 and \\\u003C12 years of age at the time of enrollment. Disease Status: Patients who participate in the efficacy expansion cohort must have bi-dimensionally measurable disease, defined as at least one lesion that can be accurately measured in at least two dimensions Patients with measurable extraneural disease only are also eligible.\n   * Phase II Age Patient must be 12 to \\\u003C\u002F=39 years at the time of enrollment.\n3. Inclusion Criteria\n\n   3.1 Uptake on \\[68Ga\\]Ga-DOTATATE PET Patients must have uptake on DOTATATE PET\u002FCT in at least one tumor lesion (corresponding to known disease) equivalent to a Krenning score ≥2 (confirmed by central radiology review).\n\n   3.2 Prior Therapy Patients must have recovered from the acute treatment related toxicities (defined as ≤ grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy, radiotherapy, or any other treatment modality prior to entering this study.\n\n   3.3 Chemotherapy Patients must have received their last dose of known myelosuppressive anticancer therapy at least 21 days prior to enrollment or at least 42 days if nitrosourea.\n\n   3.4 Investigational\u002FBiologic Agent\n\n   ●Biologic or investigational agent (anti-neoplastic): Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the investigational or biologic agent ≥ 7 days prior to study enrollment.\n\n   For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur.\n\n   ●Monoclonal Antibodies and agents with known prolonged half-lives: Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the agent ≥ 28 days prior to study enrollment.\n\n   3.5 Radiation\n\n   Patients must have had their last fraction of:\n   * Craniospinal irradiation or total body irradiation or radiation to \\> 50% of pelvis \\> 3 months prior to enrollment.\n   * Focal irradiation \\> 4 weeks prior to enrollment\n\n   3.6 Stem Cell Transplant\n\n   Patient must be:\n   * ≥ 6 months since allogeneic stem cell transplant prior to enrollment with no evidence of active graft vs. host disease\n   * ≥ 3 months since autologous stem cell transplant prior to enrollment\n\n   3.7 Growth Factors Patients must be off all colony-forming growth factor(s) for at least 1 week prior to enrollment (e.g. filgrastim, sargramostim or erythropoietin). Two weeks must have elapsed if patients received long-acting formulations.\n\n   3.8 Somatostatin analogs Patients must be off long-acting somatostatin analogs for at least 4 weeks and off short-acting somastatin analogs (i.e., octreotide) for at least 24 hours.\n\n   3.9 Neurologic Status\n   * Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment, documented by a detailed neurological exam.\n   * Patients with seizure disorders may be enrolled if seizures are well controlled.\n\n   3.10 Performance Status Karnofsky Performance Scale (KPS for \\> 16 years of age) or Lansky Performance Score (LPS for ≤ 16 years of age) assessed within two weeks of enrollment must be ≥ 50. Patients who are unable to walk because of neurologic deficits, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score\n\n   3.11 Organ Function\n\n   Patients must have adequate organ and marrow function, both for eligibility for enrollment, and to begin each subsequent cycle of Lutathera, as defined below:\n   * Adequate Bone Marrow Function as defined as:\n\n     * Absolute neutrophil count ≥ 1.0 x 109 cells\u002F L\n     * Platelets ≥100 x 109 cells\u002F L (unsupported, defined as no platelet transfusion within 7 days)\n     * Hemoglobin ≥8 g\u002Fdl (may receive transfusions)\n   * Adequate Renal Function as defined as:\n\n     * Creatinine clearance or radioisotope GFR \\>70mL\u002Fmin\u002F1.73m2 OR\n     * A serum creatinine based on (Schwartz et al. J. Peds, 106:522, 1985) age\u002Fgender as follows:\n\n       1 to \\\u003C 2 years: maximum serum creatinine 0.6 mg\u002FdL for males and females. 2 to \\\u003C 6 years: maximum serum creatinine 0.8 mg\u002FdL for males and females. 6 to \\\u003C 10 years: maximum serum creatinine 1.0 mg\u002FdL for males and females. 10 to \\\u003C 13 years: maximum serum creatinine 1.2 mg\u002FdL for males and females. 13 to \\\u003C 16 years: maximum serum creatinine 1.5 mg\u002FdL for males and 1.4 mg\u002FdL for females.\n\n       ≥ 16 years: maximum serum creatinine 1.7 mg\u002FdL for males and 1.4 mg\u002FdL for females.\n   * Adequate Liver Function as defined as:\n\n     * Total bilirubin ≤ 3 times institutional upper limit of normal (ULN) for age\n     * AST(SGOT)\u002FALT(SGPT) ≤ 3 times institutional ULN\n     * Serum albumin ≥ 2g\u002FdL\n     * Coagulation parameters: INR \\\u003C1.5 times ULN and aPTT \\\u003C1.5 times ULN unless patients are receiving therapeutic anticoagulation which affects these parameters\n   * Adequate Cardiac Function as defined as:\n\n     * Ejection fraction of ≥ 55% by echocardiogram\n     * Serum electrolytes (Sodium, Potassium, Chloride) within institutional limits of normal (patients can be on enteral supplementation)\n\n   3.12 Corticosteroids Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment, with a maximum dexamethasone dose of 2.5mg\u002Fm2\u002Fday.\n\n   3.13 Pregnancy Status Female patients of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.\n\n   3.14 Pregnancy Prevention Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study and for at least 7 months after drug cessation in females of childbearing potential and for at least 4 months after drug cessation in males of child fathering potential.\n\n   3.15 Informed Consent The patient or parent\u002Fguardian is able to understand the consent and is willing to sign a written informed consent document according to institutional guidelines.\n4. Exclusion Criteria\n\n   4.1 Confirmed bone marrow metastatic disease Patients with confirmed metastatic disease to bone marrow are ineligible.\n\n   4.2 Presence of bulky disease Patients with bulky disease on imaging as described below are ineligible. Treating physicians are encouraged to request a rapid central imaging review to confirm fulfillment of these criteria if there are questions or concerns.\n\n   Bulky disease is defined as:\n   * Tumor with evidence of clinically significant uncal herniation or midline shift.\n   * Tumor with diameter of \\>5cm in one dimension on T2\u002FFLAIR.\n   * Tumor that in the opinion of the site investigator shows significant mass effect in either the brain or spine.\n\n   Note that patients with metastatic or multi-focal disease (with exception of bone marrow) are eligible as long as no sites of disease meet above criteria for bulky disease.\n\n   4.3 Breast-feeding Nursing mothers are excluded from this study. There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Lutathera.\n\n   4.4 Concurrent Illness\n   * Patients with a history of any other malignancy, except patients with a secondary brain tumor if the patient's prior malignancy has been in remission for at least 5 years from the end of treatment.\n   * Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patient's ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results.\n   * Patients with type I diabetes.\n\n   4.5 Concomitant Medications\n   * Patients who are receiving any other anti-cancer or investigational drug therapy are ineligible.\n   * Prior or current treatment with 177Lu-DOTATATE\u002FTOC or 90Y-DOTATATE\u002FTOC.\n\n   4.6 Prisoners will be excluded from this study.\n\n   4.7 Inability to participate: Patients who in the opinion of the investigator are unwilling or unable to return for required follow-up visits, obtain follow-up studies required to assess toxicity to therapy, or adhere to drug administration plan, other study procedures, and study restrictions.\n5. Inclusion of Women and Minorities Both males and females of all races and ethnic groups are eligible for this study.","4 Years",{"count":91,"type":22},65,[59,25],"This study will evaluate the safety and efficacy of Lutathera (177Lu-DOTATATE) in patients with progressive or recurrent High-Grade Central Nervous System (CNS) tumors and meningiomas that demonstrate uptake on DOTATATE PET. The drug will be given intravenously once every 8 weeks for a total of up to 4 doses over 8 months in patients aged 4 to \\\u003C12 years (Phase I) or 12 to \\\u003C\u002F=39 years (Phase II) to test its safety and efficacy, respectively.\n\nFunding Source - FDA OOPD (grant number FD-R-0532-01)",[95,96,97,98,99,30,100,101,102,103,104,105,106],"High Grade Glioma","Meningioma","Embryonal Tumor","Medulloblastoma","Anaplastic Ependymoma","Recurrent Malignant Glioma","Recurrent Medulloblastoma","Recurrent Primary Central Nervous System Neoplasm","Refractory Diffuse Intrinsic Pontine Glioma","Refractory Malignant Glioma","Refractory Medulloblastoma","Refractory Primary Central Nervous System Neoplasm",[108,109,110],"Somatostatin Receptor","DOTATATE","Lutathera","2026-04-08",{"date":113,"type":38},"2026-04-13",{"date":115,"type":38},"2022-11-21",{"date":117,"type":22},"2033-11",{"name":119,"class":45},"Nationwide Children's Hospital",4]