[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"who-grade-iv-glioma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:who-grade-iv-glioma":35},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,4,0,[8,53,94,115],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":16,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":20,"targetDuration":4,"studyType":23,"phases":24,"briefSummary":26,"conditions":27,"keywords":37,"overallStatus":40,"whyStopped":4,"lastUpdateSubmitDate":41,"lastUpdatePostDateStruct":42,"startDateStruct":45,"completionDateStruct":47,"leadSponsor":49,"locationsCount":52},"100541748","early-phase-1-lorlatinib-for-newly-diagnosed-high-grade-glioma-with-ros-or-alk-fusion-100541748",false,"NCT06333899","Lorlatinib for Newly-Diagnosed High-Grade Glioma With ROS or ALK Fusion","A Pilot Study of Lorlatinib for Treatment of Children With Newly Diagnosed High-Grade Glioma With ROS-1 (ROS Proto-Oncogene 1, Receptor Tyrosine Kinase) or ALK (Anaplastic Lymphoma Kinase) Fusion","Inclusion Criteria:\n\n1. Patients must be ≥ 12 months and ≤ 21 years of age at the time of study enrollment on TarGeT-SCR.\n2. Diagnosis:\n\n   Patients with newly diagnosed high-grade glioma (HGG), including diffuse intrinsic pontine gliomas (DIPG), whose tumors harbor an ALK or ROS-1 fusion alteration are eligible. Patients must have had histologically verified high-grade glioma from diagnostic biopsy or resection. For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2\u002F3 of the pons, with histopathology consistent with diffuse WHO Grade 2-4. All other HGGs must be Grade 3 or 4.\n3. Disease Status:\n\n   Patients with disseminated DIPG or HGG are eligible only if the patient is to receive chemotherapy only, i.e. no craniospinal RT is intended to be given. MRI of spine must be performed if disseminated disease is suspected clinically by the treating physicians. Patients with primary spinal tumors are eligible only if the patient is to receive either chemotherapy or focal radiation therapy, i.e., no craniospinal RT is intended to be given. Patients with leptomeningeal disease only, with no definitive identifiable primary tumor, and documented ALK or ROS-1 fusion, must be discussed with the Study Chair on a case-by-case basis.\n4. Performance Level:\n\n   Karnofsky ≥ 50% for patients \\> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix I). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n5. Prior Therapy:\n\n   * Patients must not have received any prior anti-cancer chemotherapy.\n   * Prior use of corticosteroids is allowed (see below Exclusion Criteria)\n6. Organ Function Requirements 6.1 Adequate Bone Marrow Function Defined as:\n\n   * Peripheral absolute neutrophil count (ANC) ≥ 1000\u002FμL\n   * Platelet count ≥ 100,000\u002FμL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)\n   * Hemoglobin \\>8 g\u002FdL (may receive transfusions) 6.2 Adequate Renal Function Defined as:\n   * Serum creatinine within normal institutional limits OR Creatinine clearance or radioisotope GFR ≥ 70ml\u002Fmin\u002F1.73 m2 6.3 Adequate Liver Function Defined as:\n   * Total bilirubin ≤ 2 × institutional upper limit of normal\n   * AST(aspartate aminotransferase)\u002FALT(alanine transaminase) ≤ 2.5 × institutional upper limit of normal 6.4 Adequate Pulmonary Function Defined as: Pulse oximetry \\> 94% on room air if there is clinical indication for determination (e.g. dyspnea at rest).\n\n6.5Adequate Cardiac Function Defined as: QTc ≤ 470 msec (by Bazett formula) 6.6 Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled.\n\n6.7 Informed Consent: All patients and\u002For their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines\n\nExclusion Criteria:\n\n1. Pregnant or breast-feeding women will not be entered on this study due to unknown risks of fetal and teratogenic adverse events as seen in animal\u002Fhuman studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.\n\n   Females of reproductive potential must use an effective non-hormonal method of contraception, since lorlatinib can render hormonal contraceptives ineffective, during study treatment and for at least 6 months after the final dose. Males with female partners of reproductive potential must use effective contraception during treatment with lorlatinib and for 3 months after the final dose.\n2. Concomitant Medications\n\n   * Investigational Agents\u002FDrugs: Patients who have previously received or are currently receiving another investigational drug are not eligible.\n   * Anti-cancer Agents: Patients who have previously received or are currently receiving other anti-cancer agents, including chemotherapy, immunotherapy, monoclonal antibodies, biologic or targeted therapy, are not eligible\n3. Infection: Patients must not have any active, uncontrolled systemic bacterial, viral or fungal infection.\n4. Patients who have received prior solid organ transplantation are not eligible.\n5. Patients must not have malabsorption syndrome or other condition affecting oral absorption.\n6. Patients must not be receiving any treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor or inducer. Discontinue strong CYP3A inducers for 3 plasma half-lives of the strong CYP3A inducer prior to treatment with loraltinib. Moderate inducers of CYP3A4 should be avoided\n7. Avoid concomitant use of lorlatinib with certain CYP3A substrates, for which minimal concentration changes may lead to serious therapeutic failures. If concomitant use is unavoidable, increase the CYP3A substrate dosage in accordance with approved product labeling.\n8. P-glycoprotein (P-gp) substrates: Lorlatinib is considered a moderate P-gp inducer. Co-administration of lorlatinib with P-gp substrates including but not limited to digoxin should be avoided as the concentration of these drugs may be reduced by lorlatinib.\n9. 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.\n10. Patients with a known personal history of acute or chronic severe psychiatric disorders or current history of suicidal ideation and history of suicide attempt.",true,"ALL","1 Year","21 Years",{"count":21,"type":22},15,"ESTIMATED","INTERVENTIONAL",[25],"EARLY_PHASE1","The goal of this study is to determine the response of the study drug loratinib in treating children who are newly diagnosed high-grade glioma with a fusion in ALK or ROS1. It will also evaluate the safety of lorlatinib when given with chemotherapy or after radiation therapy.",[28,29,30,31,32,33,34,35,36],"High Grade Glioma","Diffuse Intrinsic Pontine Glioma","Anaplastic Astrocytoma","Infant Type Hemispheric Glioma","Glioblastoma","Glioblastoma Multiforme","WHO Grade III Glioma","WHO Grade IV Glioma","Diffuse Midline Glioma, H3K27-altered",[38,39,28,29],"ALK fusion","ROS fusion","RECRUITING","2026-06-25",{"date":43,"type":44},"2026-06-29","ACTUAL",{"date":46,"type":44},"2025-08-03",{"date":48,"type":22},"2035-06-01",{"name":50,"class":51},"Nationwide Children's Hospital","OTHER",18,{"id":54,"slug":55,"hasResults":11,"nctId":56,"briefTitle":57,"officialTitle":58,"acronym":4,"eligibilityCriteria":59,"healthyVolunteers":11,"sex":17,"minAge":60,"maxAge":61,"enrollmentInfo":62,"targetDuration":4,"studyType":23,"phases":64,"briefSummary":66,"conditions":67,"keywords":4,"overallStatus":40,"whyStopped":4,"lastUpdateSubmitDate":83,"lastUpdatePostDateStruct":84,"startDateStruct":86,"completionDateStruct":88,"leadSponsor":90,"locationsCount":93},"100528530","phase-2-study-of-olutasidenib-and-temozolomide-in-hgg-100528530","NCT06161974","Study of Olutasidenib and Temozolomide in HGG","Phase 2 Study of Olutasidenib With Temozolomide as Maintenance Therapy in Pediatric and Young Adult Patients Newly Diagnosed With High-Grade Glioma (HGG), Including Diffuse Intrinsic Pontine Glioma (DIPG), Which Harbor IDH1 Mutations","Criteria TarGeT-D study strata definitions\n\n* Stratum A: Patients with localized, intracranial, non-pontine, and non-thalamic IDH 1 mutant Astrocytoma, CNS WHO Grade 3.\n* Stratum B: Patients with localized, intracranial, non-pontine, and non-thalamic IDH 1 mutant Astrocytoma, CNS WHO Grade 4.\n* Stratum C: Patients with IDH-1 mutant DIPG, primary thalamic and spinal cord IDH-1 mutant HGG.\n\nInclusion Criteria:\n\n1. Inclusion criteria already met to enroll on TarGeT-SCR (central molecular and histopathologic screening) based on:\n\n   1.1) Age: patients must be ≥12 years and ≤39 years of age at the time of enrollment on TarGeT-SCR 1.2) Diagnosis:\n   * Patients with a newly-diagnosed IDH1-mutant HGG including DIPG are eligible. All patients must have tumor tissue from diagnostic biopsy or resection, without exceptions. The diagnosis of HGG, including DIPG, must have been confirmed through TarGeT-SCR.\n   * For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2\u002F3 of the pons, and histopathology consistent with diffuse WHO Grade 2-4 glioma.\n   * All other HGG must be WHO Grade 3 or 4.\n\n   1.3) Disease status: There are no disease status requirements for enrollment\n   * Measurable disease is not required. Patients without measurable disease are eligible.\n   * Primary spinal tumor: Patients with a primary spinal HGG are eligible.\n   * Patient must not have metastatic disease.\n2. Inclusion criteria for assignment to TarGeT-D, for all strata:\n\n2.1 Presence of at Least One Relevant Actionable Somatic Mutation in IDH1 Gene, Detailed Here:\n\n* R132H, R132C, R132S, R132G or R132L.\n* Patients whose tumors harbor other alterations in addition to IDH1 mutation will potentially be eligible following consensus recommendation by the international multidisciplinary molecular screening committee.\n* Patients with IDH2 mutations are not eligible.\n* Patients with oligodendroglioma, IDH-mutant and 1p\u002F19q-codeleted are not eligible.\n\n2.2 Weight: Patients must weigh ≥35 Kg (77 lbs) at the time of enrollment on TarGeT-D.\n\n2.3 Performance Level: Karnofsky ≥ 50% for patients \\> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n\n2.4 Prior Therapy 2.4.1 Surgery, radiation, and\u002For dexamethasone are permissible. Temozolomide administered concurrently with radiotherapy is permissible. Prior administration of bevacizumab is allowed, given at least 42-day washout period is completed prior to beginning treatment on TarGeT-D. No other prior anticancer therapy for HGG will be allowed.\n\n2.4.2 Radiation therapy requirements: RT, delivered via photon or proton beam, must have been administered at a standard dose including 54 Gy in 30 fractions for DIPG, 55-59.4 Gy in 30-33 fractions for other HGG or 45-54 Gy for primary spinal cord HGG. Any variances in the radiotherapy dose within 10% of the standard doses outlined above will be discussed with the Study Chair to confirm eligibility prior to study enrollment.\n\n2.4.3 Timing between diagnosis and start of RT: Patients must have started RT \\\u003C 42 calendar days of initial diagnosis defined as the date of diagnostic biopsy or resection; if a patient underwent two upfront surgeries (e.g., biopsy then resection or debulking), this is the date of the second surgery.\n\n* Patients in pre-maintenance phase must enroll and start treatment no later than 21 calendar days post-completion of RT.\n* Patients not in pre-maintenance phase must enroll and start treatment no later than 35 calendar days post-completion of RT.\n\n2.5 Organ Function Requirements 2.5.1 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* Hemoglobin \\> 8 g\u002FdL (may be transfused). 2.5.2 Adequate Renal Function Defined as\n* Creatinine clearance or radioisotope GFR ≥ 70ml\u002Fmin\u002F1.73 m2 OR\n* Maximum serum creatinine based on age\u002Fgender as follows: 10 to \\\u003C 13 yrs=1.2 mg\u002FdL for males and females. 13 to \\\u003C 16 yrs=1.5 mg\u002FdL for males and 1.4 mg\u002FdL for females.\n\n2.5.3 Adequate Liver Function Defined as:\n\n* Total bilirubin must be ≤ 1.5 × institutional ULN.\n* AST(SGOT)\u002FALT(SGPT) \\\u003C 3 × institutional ULN.\n* Alkaline Phosphatase \\\u003C 3 × institutional ULN. 2.5.4 Adequate Neurologic Function Defined as:\n\n  * Patients with seizure disorder may be enrolled if well-controlled on anticonvulsants that are not a strong inducer or inhibitor of CYP3A4\u002F5.\n  * Patients must be able to swallow oral medications to be eligible for study enrollment.\n\n2.6. Informed consent: All patients and\u002For their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.\n\nExclusion Criteria:\n\n1. Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to unknown potential risks of fetal and teratogenic adverse events as seen in animal studies. Pregnancy tests must be obtained in girls who are post-menarchal. Patients of childbearing or child fathering potential must agree to use one highly effective method of contraception while being treated on this study and for 3 months after completing therapy. A woman is considered of childbearing potential if she is fertile, following menarche and until becoming post-menopausal unless permanently sterile. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. Male participants should refrain from sperm donation throughout the duration of treatment and for 3 months after completion of therapy.\n\n   A highly effective contraception method is defined as one that results in a low failure rate (\\\u003C1% per year) when used consistently and correctly. The following are considered highly effective contraception methods:\n   * Combined estrogen and progesterone containing hormonal contraception associated with inhibition of ovulation.\n   * Progesterone-only hormonal contraception associated with inhibition of ovulation.\n   * Intra Uterine Device (IUD).\n   * Intra uterine hormone releasing system.\n   * Bilateral tubal occlusion.\n   * Vasectomized partner.\n   * Sexual abstinence (avoiding heterosexual intercourse).\n   * The following contraceptive measures are NOT considered effective:\n\n     * Progesterone-only hormonal contraception (birth control pill) that that does NOT stop ovulation.\n     * Male or female condom with or without spermicide.\n     * Cap, diaphragm, or sponge with spermicide.\n2. Using the following types of concomitant medications:\n\n   * Corticosteroids: Patients receiving corticosteroids are eligible. The use of corticosteroids must be reported.\n   * Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible.\n   * Anti-cancer Agents: Concurrent anti-cancer agents are not allowed with the exception of temozolomide given concurrently with RT and as protocol-instructed post RT maintenance therapy after enrollment on TarGeT-D.\n   * Anticonvulsants: Patients who are receiving enzyme inducing anticonvulsants that are strong inducers of CYP3A4\u002F5 are not eligible.\n   * Strong CYP3A4\u002F5 inducers: Patients who are receiving strong inducers of CYP3A4\u002F5 are not eligible. Strong inducers of CYP3A4\u002F5 should be avoided from 14 days prior to or 5 half-lives (whichever is longer) enrollment to the end of the study.\n   * Patients who are receiving medications known to prolong QTc interval are not eligible\n   * Selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft) should be used with caution but are not contraindicated.\n3. Other Criteria\n\n   * Infection: Patients who have an uncontrolled infection 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.\n   * Patients with known clinically significant active malabsorption syndrome or other condition that could affect absorption are not eligible.\n   * Patients with malignancy related to HIV or solid organ transplant: known history of HIV, HBV surface antigen positivity or positive HCV antibody are not eligible. Viral testing is not required unless clinically indicated in patients without a known history.\n   * Patients with prior or ongoing clinically significant illness, medical or psychiatric condition, that, in the investigator's opinion, could affect the safety of the participant, or could impair the assessment of study results are not eligible.\n   * Patients with any prior solid organ transplant are not eligible.\n   * Patients with secondary\u002Fradiation-related HGG are not eligible.\n   * Patients with metastatic\u002Fdisseminated HGG who have received CSI are not eligible.","12 Years","39 Years",{"count":63,"type":22},60,[65],"PHASE2","The goal of this study is to determine the efficacy of the study drug olutasidenib to treat newly diagnosed pediatric and young adult patients with a high-grade glioma (HGG) harboring an IDH1 mutation.\n\nThe main question the study aims to answer is whether the combination of olutasidenib and temozolomide (TMZ) can prolong the life of patients diagnosed with an IDH-mutant HGG.",[28,68,69,70,29,34,35,71,72,73,74,75,76,77,78,79,80,81,82],"Astrocytoma","Astrocytoma, Grade III","Astrocytoma, Grade IV","Metastatic Brain Tumor","Diffuse Midline Glioma, H3 K27M-Mutant","Thalamus Tumor","Spinal Tumor","IDH1 Mutation","IDH1 R132","IDH1 R132C","IDH1 R132H","IDH1 R132S","IDH1 R132G","IDH1 R132L","Oligodendroglioma","2026-06-10",{"date":85,"type":44},"2026-06-12",{"date":87,"type":44},"2025-02-01",{"date":89,"type":22},"2035-06",{"name":91,"class":92},"Rigel Pharmaceuticals","INDUSTRY",20,{"id":95,"slug":96,"hasResults":11,"nctId":97,"briefTitle":98,"officialTitle":99,"acronym":4,"eligibilityCriteria":100,"healthyVolunteers":11,"sex":17,"minAge":101,"maxAge":61,"enrollmentInfo":102,"targetDuration":4,"studyType":104,"phases":4,"briefSummary":105,"conditions":106,"keywords":4,"overallStatus":40,"whyStopped":4,"lastUpdateSubmitDate":107,"lastUpdatePostDateStruct":108,"startDateStruct":109,"completionDateStruct":111,"leadSponsor":113,"locationsCount":114},"100503755","targeted-pediatric-high-grade-glioma-therapy-100503755","NCT05839379","Targeted Pediatric High-Grade Glioma Therapy","Molecularly-Guided Phase II Umbrella Trial for Children, Adolescents, and Young Adults Newly Diagnosed With High-Grade Glioma, Including Diffuse Intrinsic Pontine Glioma","Inclusion Criteria:\n\n1. Age: Patients must be ≥12 months and ≤39 years of age at the time of enrollment onto this screening protocol.\n2. Diagnosis: Patients with newly diagnosed HGG, including DIPG are eligible. Diagnosis must have histologic confirmation from biopsy or resection. The diagnosis of HGG must have been confirmed by pathology review at the local site. For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2\u002F3 of the pons, with histopathology consistent with diffuse WHO grade 2-4 glioma (eg, diffuse astrocytoma, anaplastic astrocytoma, glioblastoma, H3K27-altered diffuse midline glioma). For all other tumors, histologic grade must be WHO grade 3-4.\n3. Disease Status: There are no disease status requirements for enrollment.\n\n   * Measurable disease is not required. Patients without measurable disease are eligible.\n   * Patients with metastatic\u002Fdisseminated or multifocal disease or gliomatosis cerebri are eligible.\n   * Patients with a primary spinal tumor are eligible.\n   * Patients with secondary, radiation related HGG are eligible.\n4. Prior Therapy for HGG: Surgery, radiation, and\u002For dexamethasone are permissible. Temozolomide concurrent with radiation is permissible. Prior administration of avastin\u002Fbevacizumab is allowed (individual treatment arms have different washout period requirements, check individual arm eligibility). No other prior anticancer therapy for HGG will be allowed.\n\n   * Participants screening for assignment to TarGeT-L may not have received radiation.\n\n   Timing from surgery to start of RT: For patients who have started RT, radiation must have started \\\u003C42 days from definitive surgery or biopsy, however it is strongly recommended patients start RT within 31 days from definitive surgery (if patient had two surgeries, radiation must have started within 31 days from second surgery).\n5. Tumor Sample Availability OR results from previous molecular profiling\u002Ftargeted sequencing\n\n   * If a patient screens through OPTION #1, tumor sample in addition to normal comparator tissue (peripheral blood, saliva, or buccal swab) must be submitted for comprehensive molecular screening at the time of screening enrollment.\n   * If a patient screens through OPTIONS #2 or #3, results from previously performed molecular profiling must be submitted following enrollment. It is highly recommended that results be uploaded within 7 days of enrollment (if results are available at time of enrollment) or within 7 days of results becoming available (if pending at time of enrollment) to allow adequate time for central review.\n6. Informed Consent: All patients and\u002For their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.\n7. Enrollment timeline: Patients are eligible to enroll on the TarGeT-SCR anytime between diagnosis and the following specific timepoints post completion of RT (if relevant)\n\n   * Patients screening through OPTION #1 are eligible to enroll anytime between diagnosis and 10 days post RT (if completing RT).\n   * Patients screening through OPTIONS #2 or #3 are eligible to enroll anytime between diagnosis and 21 days post RT (if completing RT).\n   * Participants screening for TarGeT-L (lorlatinib) are eligible to enroll on TarGeT-SCR anytime between diagnosis and 31 days post definitive surgery (to allow time for molecular review).\n\nHowever, it is important to note the following:\n\n* For treatment protocols that include targeted therapy administered concurrently with RT, patients must start treatment within 10 calendar days of starting RT.\n* For treatment protocols that only include maintenance\u002Fadjuvant therapy (no systemic therapy given concurrently with radiation), patients must start treatment by 35 days post RT\n\n  #SCREENING OPTIONS\n* OPTION1: Molecular screening through CONNECT TarGeT Clinical Testing Laboratories\n* OPTION2: Molecular screening through a national comprehensive tumor profiling program\n* OPTION3: Clinically validated targeted sequencing or focused profiling\n\nExclusion Criteria:\n\n-Tumors that do not meet HGG and DIPG diagnoses specified above","12 Months",{"count":103,"type":22},350,"OBSERVATIONAL","The goal of this study is to perform genetic sequencing on brain tumors from children, adolescents, and young adult patients who have been newly diagnosed with a high-grade glioma. This molecular profiling will decide if patients are eligible to participate in a subsequent treatment-based clinical trial based on the genetic alterations identified in their tumor.",[28,29,30,32,33,72,71,34,35],"2026-06-08",{"date":83,"type":44},{"date":110,"type":44},"2024-08-02",{"date":112,"type":22},"2034-08-28",{"name":50,"class":51},21,{"id":116,"slug":117,"hasResults":11,"nctId":118,"briefTitle":119,"officialTitle":120,"acronym":4,"eligibilityCriteria":121,"healthyVolunteers":11,"sex":17,"minAge":101,"maxAge":61,"enrollmentInfo":122,"targetDuration":4,"studyType":23,"phases":124,"briefSummary":125,"conditions":126,"keywords":4,"overallStatus":40,"whyStopped":4,"lastUpdateSubmitDate":128,"lastUpdatePostDateStruct":129,"startDateStruct":131,"completionDateStruct":133,"leadSponsor":134,"locationsCount":93},"100504051","phase-2-study-of-ribociclib-and-everolimus-in-hgg-and-dipg-or-ribociclib-and-temozolomide-in-dhg-h3g34-mutant-100504051","NCT05843253","Study of Ribociclib and Everolimus in HGG and DIPG or Ribociclib and Temozolomide in DHG, H3G34-mutant","Phase 2 Study of Ribociclib-Containing Post-Radiotherapy Combinations in Pediatric and Young Adult Patients Newly Diagnosed With High-Grade Glioma, Including Diffuse Intrinsic Pontine Glioma: Ribociclib and Everolimus for HGG\u002FDIPG Which Harbor Alterations of the Cell Cycle and\u002For PI3K\u002FmTOR Pathways AND Ribociclib and Temozolomide for DHG, H3G34-mutant","TarGeT-A study strata definitions Part1: Initial Feasibility Study for the combination of ribociclib PfOS formulation with everolimus: Enrollment on this cohort will be limited to patients aged \\\u003C21 years with primary intracranial localized HGG and DIPG\n\nPart 2\n\n* Stratum A: Patients with localized, intracranial, non-pontine, and non-thalamic HGG (who do not meet criteria for strata C-D)\n* Stratum B: Patients with DIPG\n* Stratum C: Patients with primary thalamic, spinal cord, and\u002For secondary\u002Fradiation-related HGG.\n* Stratum D: Patients with metastatic\u002Fdisseminated HGG, multifocal HGG, and\u002For gliomatosis cerebri who received CSI.\n\nStratum E\n\n* Stratum E: Patients with localized DHG, H3G34-mutant.\n\nInclusion Criteria:\n\n1. Inclusion criteria already met to enroll on TarGeT-SCR (central molecular and histopathologic screening) based on:\n\n   1.1) Age: patients must be ≥12 months and ≤39 years of age at the time of enrollment on TarGeT-SCR. For the Part 1 Initial Feasibility Cohort (receiving ribociclib and everolimus) only: patients must be \\\u003C21 years of age at the time of enrollment on this protocol.\n\n   1.2) Diagnosis: patients with newly-diagnosed HGG, including DIPG are eligible. All patients must have histologic confirmation tumor tissue from diagnostic biopsy or resection, without exceptions. The diagnosis of HGG, including DIPG, must have been confirmed through TarGeT-SCR:\n   * For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2\u002F3 of the pons, with histopathology, consistent with diffuse WHO grade 2-4 glioma\n   * All other HGGs must be WHO grade 3 or 4.\n\n   1.3) Disease status: There are no disease status requirements for enrollment\n   * Patients without measurable disease are eligible.\n   * Patients with metastatic or multifocal disease or gliomatosis cerebri who received upfront CSI are eligible\n   * Patients with a primary spinal HGG are eligible\n   * Patients with secondary, radiation-related HGG are eligible.\n2. Inclusion criteria for assignment to TarGeT-A, for all strata:\n\n2.1) Presence of at least one relevant actionable somatic alteration, detailed here:\n\n* Pathogenic alterations presumed to cause activation of cell cycle:\n* Amplification of CDK4 or CDK6\n* Deletion of CDKN2A, CDKN2B, or CDKN2C\n* Amplification of CCND1 or CCND2\n* Pathogenic alterations presumed to cause activation of the PI3K\u002FmTOR pathway:\n* Deletion or mutation of PTEN\n* Mutation or amplification of PIK3CA\n* Mutation of PIK3R1\n* Deletion or mutation of TSC1 or TSC2\n* Patients with evidence of homozygous (biallelic) RB1 loss by sequencing are excluded from TarGeT-A\n* Patients whose tumors harbor other alterations suspected to activate the cell cycle and\u002For PI3K\u002FmTOR pathway could potentially also be eligible, but only following consensus recommendation by the international multidisciplinary molecular screening committee.\n* For Stratum E: H3G34 (R\u002FV) mutation\n\n2.2) Performance Level: Karnofsky ≥ 50% for patients \\> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of ag. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n\n2.3) Prior Therapy for HGG:\n\n* Surgery, RT, dexamethasone are permissible. Temozolomide administered concurrently with RT is permissible. Avastin\u002Fbevacizumab use is permitted given the last dose was administered \\> 21 days prior to enrollment. No other prior anticancer therapy for HGG will be allowed.\n* Patients must have received photon or proton RT.\n* Patients must have started RT \\\u003C 42 calendar days from initial diagnosis defined as the date of diagnostic biopsy or resection. If a patient underwent 2 upfront surgeries (e.g., biopsy then resection or debulking), this is the date of the second surgery.\n* RT delivered via photon or proton beam, must have been administered at a standard dose including (54 Gy in 30 fractions for DIPG, 54-59.4 Gy in 30-33 fractions), 45 Gy-54 Gy for primary spinal disease, and\u002For 36 Gy-39.6 Gy craniospinal for patients with spinal or leptomeningeal metastatic disease with supplemental boost to 45-54 Gy for metastasis within the thecal sac and 54 Gy-60 Gy for intracranial metastasis. Any variances in the radiotherapy dose within 10% of the standard doses outlined above will be discussed with the Sponsor-Investigator to confirm eligibility prior to study enrollment.\n* Patients must enroll and start treatment No later than 35 calendar days post-completion of RT. The earliest patients can begin protocol treatment is 28 calendar days post-completion of RT.\n\n2.4) Organ Function Requirements\n\n2.4.1) 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* Hemoglobin \\>8 g\u002FdL (may be transfused)\n\n2.4.2) Adequate Renal Function Defined as:\n\n* Creatinine clearance or radioisotope GFR ≥ 70ml\u002Fmin\u002F1.73 m2 OR\n* Maximum serum creatinine based on (Schwartz et al. J. Peds, 106:522, 1985) age\u002Fgender as follows: 1 to \\\u003C 2 years=0.6 mg\u002FdL for males and females; 2 to \\\u003C 6 years=0.8 mg\u002FdL for males and females; 6 to \\\u003C 10 years= 1.0 mg\u002FdL for males and females; 10 to \\\u003C 13 years=1.2 mg\u002FdL for males and females. 13 to \\\u003C 16 years=1.5 mg\u002FdL for males and 1.4 mg\u002FdL for females.\n\n2.4.3) Adequate Liver Function Defined as:\n\n* Total bilirubin must be ≤ 1.5 times institutional upper limit of normal for age\n* AST(SGOT)\u002FALT(SGPT) ≤ 3 times institutional upper limit of normal\n* Serum albumin ≥ 2g\u002FdL\n\n2.4.4) Adequate Cardiac Function Defined as:\n\n* Ejection fraction of ≥ 50% by echocardiogram\n* QTc ≤ 450 msec (by Bazett formula)\n\n2.4.5) Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if well-controlled on anticonvulsants that are not strong inducers or inhibitors of CYP3A4\u002F5.\n\n2.4.6) Adequate Pulmonary Function Defined as: No evidence of dyspnea at rest, and a pulse oximetry \\>94% on room air if there is clinical indication for determination.\n\n2.5) Ability to take medications by mouth: For ribociclib and everolimus strata, patients must be able to take study medications by mouth as administration via NG\u002FNJ\u002FG tube is not allowed.\n\n2.6) Informed Consent: All patients and\u002For their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines\n\n2.7) Contraception: Male and female patients of childbearing potential must be willing to use a highly effective contraception method.\n\nExclusion Criteria\n\n1. Pregnant or Breast-Feeding Pregnant or breast-feeding women will not be entered on this study due to known potential risks of fetal and teratogenic adverse events as seen in animal\u002Fhuman studies. Pregnancy tests must be obtained in girls who are post-menarchal. Patients of childbearing or child fathering potential must agree to use at least one highly effective method of contraception while being treated on this study and for 3 months after completing therapy. A woman is considered of childbearing potential if she is fertile, following menarche and until becoming post-menopausal unless permanently sterile. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. Male participants should refrain from sperm donation throughout the duration of treatment and for 3 months after completion of therapy\n\n   A highly effective contraception method is defined as one that results in a low failure rate (\\\u003C1% per year) when used consistently and correctly. The following are considered highly effective contraception methods:\n   * Combined estrogen and progesterone containing hormonal contraception associated with inhibition of ovulation.\n   * Progesterone-only hormonal contraception associated with inhibition of ovulation.\n   * Intra Uterine Device (IUD)\n   * Intra Uterine hormone releasing system\n   * Bilateral tubal occlusion\n   * Vasectomized partner\n   * Sexual abstinence (avoiding having heterosexual intercourse) The following contraceptive measures are NOT considered effective\n   * Progesterone-only hormonal contraception (birth control pill) that that does NOT stop ovulation\n   * Male or female condom with or without spermicide\n   * Cap, diaphragm or sponge with spermicide\n2. Concomitant Medications\n\n   * Patients receiving corticosteroids are eligible. The use of corticosteroids must be reported.\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, with the exception of temozolomide given concurrently with RT only.\n   * Patients who are receiving enzyme inducing anticonvulsants that are strong inducers or inhibitors of CYP3A4\u002F5 are not eligible.\n   * Patients who are receiving strong inducers or inhibitors of CYP3A4\u002F5 are not eligible and should be avoided from 14 days prior to enrollment to the end of the study.\n   * Patients who are receiving medications known to prolong QTc interval are not eligible.\n   * Patients who are receiving therapeutic anticoagulation with warfarin or other coumadin-derived anticoagulants are not eligible. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed as long as the patient has adequate coagulation defined as aPTT \\\u003C 1.5Xs ULN and INR \\\u003C 1.5.\n3. Patients who have an uncontrolled infection are not eligible.\n4. 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.\n5. Patients with known clinically significant active malabsorption syndrome or other condition that could affect absorption are not eligible.\n6. Patients with prior or ongoing clinically significant medical or psychiatric condition that, in the investigator's opinion, could affect the safety of the subject, or could impair the assessment of study results are not eligible.",{"count":123,"type":22},120,[65],"The goal of this study is to determine the efficacy of the 1) ribociclib and everolimus to treat pediatric and young adult patients newly diagnosed with a high-grade glioma (HGG), including DIPG, that have genetic changes in pathways (cell cycle, PI3K\u002FmTOR) that these drugs target or 2) ribociclib and temozolomide to treat pediatric and young adult patients newly diagnosed with diffuse hemispheric glioma (DHG), H3G34-mutant.\n\nThe main question the study aims to answer is whether the combinations of ribociclib and everolimus or ribociclib and temozolomide can prolong the life of patients diagnosed with HGG\u002FDIPG or DHG H3G34-mutant.",[28,29,30,32,33,72,71,34,35,127],"Diffuse Hemispheric Glioma, H3 G34-Mutant","2026-05-27",{"date":130,"type":44},"2026-05-29",{"date":132,"type":44},"2024-08-22",{"date":112,"type":22},{"name":50,"class":51}]