[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"neurofibromatosis-1-nf1\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:neurofibromatosis-1-nf1":27},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,48],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":13,"acronym":14,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":28,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":36,"lastUpdatePostDateStruct":37,"startDateStruct":40,"completionDateStruct":42,"leadSponsor":44,"locationsCount":47},"100633051","phase-2-efficacy-of-mirdametinib-alone-or-combination-with-radiotherapy-for-germline-and-sporadic-nf1-altered-high-grade-glioma-100633051",false,"NCT07521657","Efficacy of Mirdametinib Alone or Combination With Radiotherapy for Germline and Sporadic NF1-Altered High-Grade Glioma","NF118","Inclusion Criteria:\n\n* Tumor diagnosis:\n\n  * Cohort 1 (applies to non-NF1 related GBM): GBM, IDH-wildtype grade 4 of brain or spinal cord by WHO 2021 central nervous system tumor diagnostic criteria52 that is recurrent after irradiation and first-line chemotherapy (if appropriate). Any number of prior recurrences is acceptable. Tumor Next Generation Sequencing (NGS) must demonstrate at least one pathogenic\u002Flikely pathogenic NF1 alteration (known or suspected to confer loss of function) at time of first or recurrent surgery that could putatively confer loss-of-function.\n  * Cohort 2 (applies to participants with NF1): Pathology consistent with GBM, IDH-wildtype grade 4 by WHO 2021 CNS tumor diagnostic criteria or HGG with somatic TP53 mutation (brain or spinal cord). Participants may not have received any therapy beyond surgical resection for the target HGG.\n  * Cohort 3 (applies to participants with NF1): HGAP (including low-grade glioma classified as HGAP by methylation profiling) or other HGG not meeting criteria for Cohort 2. Participants may not have received prior therapy for the HGG.\n* Neurofibromatosis 1:\n\n  * Cohort 1: Participants may not have a diagnosis of NF1.\n  * Cohort 2\u002F3: All participants must have a diagnosis of NF1 based on the 2021 revised consensus criteria.\n* Age: Cohort 1: Participants must be ≥ 18 years of age at the time of enrollment. Cohorts 2\u002F3: Participants must be ≥ 12 years of age at the time of enrollment.\n* Performance Level: Participants must have performance status of \\>= 60 using Karnofsky for participants aged \\>= 16 years, and Lansky for participants \\\u003C 16 years of age.\n* Cohort 3: Participants must have measurable disease by RANO 2.0 HGG or LGG criteria on baseline MRI.\n* Participants must have available archival tissue from the HGG or GBM of interest. Tissue blocks strongly preferred and will be returned to sending site at end of study. Exceptions may be made following discussion with study team if tissue has been exhausted and methylation profiling already performed.\n* Organ Function Requirements:\n\n  * Adequate bone marrow function defined as:\n\n    * Absolute neutrophil count \\> 1,000\u002FmcL\n    * Platelets \\> 100,000\u002FmcL\n    * Hemoglobin \\> 9 g\u002FdL\n  * Adequate renal function defined as:\n\n    * Creatinine ≤ 1.5x institutional upper limit of normal based on age\u002Fgender OR\n    * Estimated glomerular filtration rate (eGFR) ≥60 mL\u002Fmin\u002F1.73 m2 calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation\n  * Adequate liver function defined as:\n\n    * Total bilirubin (sum of conjugated + unconjugated) \\\u003C=1.5x upper limit of normal (ULN) for age (for participants with Gilbert's disease ≤3x ULN), and\n    * Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) \\\u003C 2.5x the upper limit of normal (ULN).\n    * PT\u002FINR and partial thromboplastin time (PTT) test \\\u003C 1.5x the laboratory ULN\n  * CPK level ≤ 1.5x institutional ULN\n  * Blood pressure within upper limit of normal as defined below. Antihypertensives are permissible to achieve blood pressure within ULN, however must be on stable antihypertensive regimen with no adjustments within 30 days of enrollment.\n\n    * In adolescents, a blood pressure (BP) ≤ 90th percentile for age, height, and sex.\n    * In adults (\\>=18 years of age), a systolic blood pressure consistently ≤150 mmHg and a diastolic pressure consistently ≤ 100 mmHg.\n* The following intervals from previous treatments are required to be eligible for all cohorts:\n\n  * 12 weeks from an anti-VEGF therapy\n  * 4 weeks from a nitrosourea chemotherapy\n  * 3 weeks from a non-nitrosourea chemotherapy\n  * 2 weeks or 5 half-lives from any investigational (not FDA-approved) agents\n  * 2 weeks from administration of a non-cytotoxic, FDA-approved agent (e.g., erlotinib, hydroxychloroquine, etc.)\n* The following intervals from previous radiation are required to be eligible for each cohort:\n\n  * Cohort 1: 24 weeks from prior radiation for the same tumor.\n  * Cohort 2: 24 weeks from prior radiation for any other tumor. Note: Participants who received prior radiation for which the expected new prescription isodose field will overlap with the high dose field will be excluded.\n  * Cohort 3: 12 weeks from any radiation therapy.\n* Written informed consent must be obtained from all participants (\\>18 years of age) or their legal guardians (if the participant is \\\u003C18 years of age).\n* Participants must be maintained on a stable or decreasing dose of systemic corticosteroid regimen (no increase for 5 days) prior to baseline MRI. Topical and inhaled steroid treatment is allowed.\n* Sexually active fertile participants and their partners must agree to use highly effective methods of contraception e.g., hormonal oral contraception, injectables, intrauterine device, surgical sterilization including vasectomy, or hormonal implant with barrier methods (male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 6 weeks after the last dose of study treatment. Barrier methods alone are insufficient. True sexual abstinence is an acceptable method of birth control for both men and women. Persons of childbearing potential will be given a pregnancy test within 72 hours prior to the first dose of study treatment and must have a negative urine or serum pregnancy test.\n* Female participants must agree not to harvest or donate eggs (ova, oocytes) and male participants must agree to not harvest or donate sperm for the purpose of reproduction during the treatment period and for at least 6 months after the last dose of study treatment. The Investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study treatment.\n\nExclusion Criteria:\n\n* Tumor positive for pathogenic IDH-mutation, H3.1 or H3.3 mutation, or BRAF alteration.\n* Participant has not recovered to ≤ Grade 1 non-hematologic toxic effects of prior therapy before starting study treatment. Note: Stable chronic conditions (≤ Grade 2) that are not expected to resolve (such as neuropathy, myalgia, alopecia, prior therapy-related endocrinopathies) are exceptions and may enroll.\n* Prior MEK inhibitor therapy:\n\n  * Cohort 1: Prior MEK inhibitor therapy contraindicated\n  * Cohorts 2\u002F3: Prior MEK inhibitor therapy to target glioma contraindicated (even if the target tumor was previously suspected or biopsy-proven low-grade glioma). No oral MEK inhibitor therapy in the past 12 months for other manifestations of NF1 (including non-target glioma).\n  * Topical MEK inhibitor within 12 months is not an exclusion but cannot be continued while on study.\n* Impaired cardiovascular function or clinically significant cardiovascular disease including, but not limited to, any of the following:\n\n  * History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) ≤ 180 days prior to start date;\n  * Congestive heart failure requiring treatment (New York Heart Association Grade ≥ 2);\n  * Left ventricular ejection fraction (LVEF) \\\u003C 50% as determined by MUGA or ECHO;\n  * Baseline QTc interval \\> 450 msec;\n  * History or presence of clinically significant cardiac arrhythmias (including resting bradycardia, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia).\n* Impairment of gastrointestinal function or disease which may significantly alter the absorption of study drug (e.g., active ulcerative disease, uncontrolled vomiting or diarrhea, malabsorption syndrome, small bowel resection with decreased intestinal absorption), or recent (≤ 90 days) history of a partial or complete bowel obstruction, or other conditions that will interfere significantly with the absorption of oral drugs.\n* History of recent (≤ 90 days) thromboembolic or cerebrovascular event such as transient ischemic attack, cerebrovascular accident, or hemodynamically significant (massive or sub-massive) deep vein thrombosis or pulmonary emboli (DVT\u002FPE). Note: Participants with DVT\u002FPE that does not result in hemodynamic instability may enroll as long as they are anticoagulated for at least 4 weeks.\n* Other Malignancies:\n\n  * Cohort 1: Participants must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder. Participants with other malignancies must be disease-free for \\> 2 years.\n  * Cohorts 2\u002F3: Participants must have no current or prior diagnosis of malignant peripheral nerve sheath tumor or other malignancy requiring treatment in the last 2 years. A stable or previously treated LGG is acceptable.\n* Ophthalmologic conditions:\n\n  * Current or history of central serous retinopathy.\n  * Current or history of retinal vein occlusion.\n  * Known intraocular pressure (IOP) \\>21 mmHg (or ULN adjusted by age) or uncontrolled glaucoma (irrespective of IOP). Participants with known glaucoma and increased IOP who do not have meaningful vision (light perception only or no light perception) and are not experiencing pain related to the glaucoma, may be eligible after discussion with the study chair. Participants with orbital plexiform neurofibromas should have IOP measured prior to enrollment.\n  * Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or long-standing orbito-temporal PN (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study.\n  * Note: Mild and controlled\u002Fstable age-related macular degeneration or non-proliferative diabetic retinopathy may be acceptable at the investigator's discretion after consultation with the ophthalmologist.\n  * Participants with any other significant abnormality on ophthalmic examination should be discussed with the Study Chair for potential eligibility.\n* Other clinically significant disorders that would preclude safe study participation, including:\n\n  * Active infection,\n  * Poorly controlled HIV. HIV testing will not be required as part of this trial, unless HIV is clinically suspected,\n  * Poorly controlled Hepatitis B or Hepatitis C\n* Pregnant or lactating women.\n* Previously identified allergy or hypersensitivity to components of the study treatment formulations.\n* Current use of a prohibited medication (including herbal medications, supplements, or foods), or use of a prohibited medication ≤ 7 days prior to the start of study treatment.\n* Use of any medications or substances that are strong inhibitors of breast cancer resistance protein (BCRP) \\\u003C 14 days prior to the study treatment initiation.\n* Participants who have other medical, social or concurrent challenges that are likely to negatively impact their ability to meet all of the trial obligations and therefore may increase the risk of safe participation in the study.","ALL","12 Years","89 Years",{"count":20,"type":21},55,"ESTIMATED","INTERVENTIONAL",[24],"PHASE2","This is a phase 2, open label, parallel multi-arm study of mirdametinib in combination with radiation in participants with recurrent sporadic glioblastoma (GBM) harboring NF1 alterations (Cohort 1); participants with NF1 with a newly diagnosed GBM (Cohort 2); mirdametinib alone in other NF1-associated High-Grade Gliomas (Cohort 3).",[27],"Neurofibromatosis 1 (NF1)",[29,30,31,32,33,34],"Neurofibromatosis 1","NF1","gliomas","glioblastoma","High-Grade Gliomas (HHG)","High-Grade Astrocytoma with Piloid Features (HGAP)","NOT_YET_RECRUITING","2026-04-03",{"date":38,"type":39},"2026-04-13","ACTUAL",{"date":41,"type":21},"2026-08-01",{"date":43,"type":21},"2031-08-01",{"name":45,"class":46},"University of Alabama at Birmingham","OTHER",1,{"id":49,"slug":50,"hasResults":11,"nctId":51,"briefTitle":52,"officialTitle":53,"acronym":54,"eligibilityCriteria":55,"healthyVolunteers":11,"sex":16,"minAge":56,"maxAge":4,"enrollmentInfo":57,"targetDuration":4,"studyType":22,"phases":59,"briefSummary":61,"conditions":62,"keywords":65,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":71,"lastUpdatePostDateStruct":72,"startDateStruct":74,"completionDateStruct":76,"leadSponsor":78,"locationsCount":47},"100572634","phase-1-early-phase-study-evaluating-mek-and-mdm2-inhibition-in-patients-with-nf1-and-mpnst-100572634","NCT06735820","Early Phase Study Evaluating MEK and MDM2 Inhibition in Patients With NF1 and MPNST","Early Phase Study to Evaluate the MEK Inhibitor Selumetinib With the MDM2 Inhibitor APG-115 in Patients With Neurofibromatosis Type 1 and Pre-malignant and Malignant Peripheral Nerve Sheath Tumors","MEKMDM2","Inclusion Criteria:\n\n* AGE: Part A and C: ≥ 18 years of age AGE: Part B: ≥12 years (minimum BSA ≥0.55m2)\n* Part A and B: Patients with unresectable or metastatic histologically confirmed NF1 associated MPNST. Part C: Patients with NF1 and ANNUBP. Diagnostic criteria based on Miettinen et al, Human Pathol:\n* MEASURABLE DISEASE: Patients must have measurable disease by RECISTv1.1. Baseline radiologic scans must be performed within 4 weeks of starting treatment.\n* Therapeutic options: Parts A and B: Patients must have experienced progression after one or more prior regimens of cytotoxic chemotherapy. Patients who have refused cytotoxic chemotherapy or for whom treatment on this protocol prior to receiving cytotoxic chemotherapy is felt to be in the best interest for the patient by the local investigator will also be eligible. Part C: Patients with ANNUBP that are planned for surgical resection\n* PRIOR THERAPY\n\n  * Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering on this study excluding chronic grade 1 toxicities and alopecia.\n  * No limitation on the number of prior chemotherapy regimens that the patient may have received prior to study entry.\n  * Myelosuppressive chemotherapy: The last dose of all myelosuppressive anticancer drugs must be at least 3 weeks (≥21 days) prior to study entry (42 days if prior nitrosourea).\n  * Immunotherapy: The last dose of immunotherapy (monoclonal antibody or vaccine) must be at least 4 weeks prior to study entry.\n  * Anti-cancer agents not known to be myelosuppressive (e.g not associated with reduced platelets or ANC count): ≥7 days after the last dose of the agent .\n  * Radiation therapy: The last dose of radiation to more than 25% of marrow containing bones (pelvis, spine, skull) must be at least 4 weeks prior to study entry. The last dose of all other local palliative (limited port) radiation must be at least 2 weeks prior to study entry.\n  * Stem Cell Transplantation. At least 2 months post-autologous stem cell transplant or at least 3 months post-allogeneic transplant and recovered from toxicities without evidence of graft versus host disease and on stable doses of immunosuppressive medications, if required.\n  * Growth Factors. The last dose of colony stimulating factors, such as filgrastim, sargramostim, and erythropoietin, must be at least 1 week prior to study entry, the last dose of long-acting colony stimulating factors, such as pegfilgrastim, must be at least 2 weeks prior to study entry.\n* Concurrent therapies: No other anti-cancer therapy (chemotherapy, biological therapy, radiation therapy) permitted.\n* PERFORMANCE STATUS\n\n  * Lansky\u002FKarnofsky performance level ≥ 50% . Participants who are wheelchair bound or have limited mobility secondary to a need for mechanical breathing support (such as an airway PN requiring tracheostomy or continuous positive airway pressure) who must have a Lansky performance of ≥ 40 (Appendix related to performance status scale).\n  * For patients ≥18: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.\n  * Patients who are unable to walk because of paralysis or motor weakness, but who are able to use a wheelchair will be considered ambulatory for the purpose of calculating the performance score.\n* HEMATOLOGIC FUNCTION\n\n  * Hemoglobin ≥9.0 g\u002FdL (transfusion permissible)\n  * Peripheral absolute neutrophil count (ANC) of ≥1000\u002FμL\n  * Platelet count ≥75,000\u002FμL (transfusion independent (no transfusion within at least 7 days prior to enrollment))\n* HEPATIC FUNCTION\n\n  * Total bilirubin must be ≤ 1.5 times the upper limit of normal (ULN) or ≤3×ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia).\n  * SGOT (AST)\u002FSGPT (ALT) must be ≤ 3.0 times ULN\n* RENAL FUNCTION: Serum creatinine ≤ 1.5 times ULN or creatinine clearance \\>60 ml\u002Fmin\u002F1.73m2\n* CARDIAC FUNCTION:\n\n  * Normal ejection fraction by ECHO by institutional normal (within 4 weeks of enrollment)\n  * QTc ≤ 450msec (within 4 weeks of enrollment)\n* Fertile men and women of childbearing potential must agree to use an effective method of birth control.\n* CNS DISEASE: Patients with central nervous system disease are eligible for enrollment if they have received prior radiotherapy or surgery to sites of CNS metastatic disease and are without evidence of clinical progression or stable disease at 4 weeks.\n\nExclusion Criteria:\n\n* History of another primary malignancy except for:\n\n  * A malignancy treated with curative intent and with no known active disease ≥2 years before the first dose of the study intervention and of low potential risk of recurrence.\n  * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease\n  * Adequately treated carcinoma in situ without evidence of disease\n  * Stable optic pathway glioma or low-grade glioma not receiving active therapy\n* History of leptomeningeal carcinomatosis\n* Patients receiving other anti-cancer agents are not eligible.\n* Patients who cannot swallow whole pills.\n* Current or prior use of immunosuppressive medications within 14 days prior to study entry. The following are exceptions to this criterion:\n* Intranasal, inhaled, topical steroids or local steroid injection (e.g., intra-articular injection)\n* Systemic corticosteroids used at physiologic doses not to exceed 10mg\u002Fday of prednisone or its equivalent\n* Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).\n* Any recent major surgery within a minimum of 4 weeks prior to starting drug therapy. Placement of vascular access device, percutaneous tumor biopsy, or bone marrows are not considered major surgical procedures and no minimum time frame prior to starting study drug therapy is required.\n* Patients who have any known severe and\u002For uncontrolled medical conditions or other conditions that could affect their participation in the study such as:\n* Severely impaired lung function defined as spirometry and DLCO that is 50% of the normal predicted value corrected for hemoglobin and alveolar volume and\u002For O2 saturation that is 88% or less at rest on room air. For patients who do NOT have respiratory symptoms (e.g., dyspnea at rest, known requirement for supplemental oxygen), pulmonary function test is not required.\n* Cardiac conditions as follows:\n* Uncontrolled hypertension (blood pressure ≥≥140\u002F90 mmHg despite medical therapy.\n* For pediatric patients: blood pressure ≥95th percentile for age, height, and gender measured as described in Appendix VIII\n* Known inherited coronary disease;\n* For studies with pediatric patients: History of angina or acute coronary syndrome; Acute coronary syndrome within 6 months prior to starting drug therapy\n* Uncontrolled angina despite medical therapy (Canadian Cardiovascular Society grade II-IV despite medical therapy (Appendix IV))\n* Symptomatic heart failure NYHA Class II-IV prior or current cardiomyopathy or severe valvular disease (Appendix V)\n* Prior or current cardiomyopathy including but not limited to the following\n\n  * Known hypertrophic cardiomyopathy\n  * Known arrhythmogenic right ventricular cardiomyopathy\n  * Previous moderate or severe impairment of left ventricular systolic function (LVEF \\\u003C45% on echocardiography or equivalent of MUGA) even if full recovery has occurred\n* Symptomatic or uncontrolled atrial fibrillation despite treatment or asymptomatic sustained ventricular tachycardia.\n* Active primary immunodeficiency\n* Ophthalmological conditions as follows (ophthalmology exam within 4 weeks of study enrollment)\n* Current or past history of retinal pigment epithelial detachment\u002Fcentral serous retinopathy or retinal vein occlusion\n* Known intraocular pressure (IOP)\\>21 mmHg (or ULN adjusted by age) or uncontrolled glaucoma.\n* Any other significant abnormality on ophthalmic examination that would make the subject unsuitable for enrolment into the study, as assessed by the investigator.\n* Subjects with ophthalmological findings secondary to long standing optic pathway glioma (such as visual loss, optic nerve pallor, or strabismus) or long standing orbito-temporal PN (such as vision loss, strabismus) will not be considered a significant abnormality for purposes of this study.\n* Any Supplementation with vitamin E in the 7 days prior to initiation of selumetinib.\n* Hypersensitivity to investigational products, or drugs with similar chemical structures to investigational products.\n* Patients unwilling or unable to comply with the protocol.\n* Seville orange, star fruit, grapefruit juice, St. Johns' Wort use are not allowed while on study.\n* Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of selumetinib.\n* Receiving herbal supplements or medications known to be strong or moderate inhibitors or inducers of the cytochrome P450 (CYP)2C19 and CYP3A4 enzymes or fluconazole unless such products can be safely discontinued at least 14 days or 5 half-lives (whichever is longer) before the first dose of study medication.\n* Persistent toxicities (CTCAE Grade ≥2) caused by previous anticancer therapy, excluding hair changes such as alopecia or hair lightening.\n* Currently pregnant (confirmed with positive pregnancy test) or breastfeeding (lactation must be discontinued throughout the period of the study and until at least one week after the last dose of study intervention)","18 Years",{"count":58,"type":21},45,[60,24],"PHASE1","This is a phase 0\u002F1\u002F2, multi-site study to evaluate the MEK inhibitor Selumetinib with the MDM2 Inhibitor APG-115 in patients with Neurofibromatosis Type 1 and pre-malignant and malignant peripheral nerve sheath tumors",[63,27,64],"Malignant Peripheral Nerve Sheath Tumor (MPNST)","Atypical Neurofibroma",[30,66,67,68,69,70],"MPNST","MEK inhibitor","MDM2 inhibitor","atypical neurofibroma","ANNUBP","2025-07-01",{"date":73,"type":39},"2025-07-03",{"date":75,"type":21},"2025-10-01",{"date":77,"type":21},"2028-10-01",{"name":79,"class":46},"AeRang Kim"]