[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"plexiform-neurofibroma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:plexiform-neurofibroma":29},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,5,0,[8,43,68,97,128],{"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":30,"whyStopped":4,"lastUpdateSubmitDate":31,"lastUpdatePostDateStruct":32,"startDateStruct":35,"completionDateStruct":37,"leadSponsor":39,"locationsCount":42},"100530589","phase-2-selumetinib-for-the-prevention-of-plexiform-neurofibroma-growth-in-nf-type-1-100530589",false,"NCT06188741","Selumetinib for the Prevention of Plexiform Neurofibroma Growth in NF Type 1","Phase 2 Trial of Selumetinib for the Prevention of Plexiform Neurofibroma Growth and Morbidity in Neurofibromatosis Type 1","NF114","PART 1:\n\nInclusion Criteria:\n\n1. Age: \\> 1 (\\>12 months) and ≤8 years of age at the time of study enrollment.\n2. Diagnosis: Participants with a diagnosis of NF1 based on the 2021 revised consensus criteria \\[52\\] and\n3. No known PN (prior to enrollment on Part 1). Participants for whom there is clinical suspicion for a PN (e.g., subtle facial asymmetry or large overlying hyperpigmented area) may be included in the study after discussion with the Study Chair so long as they have not previously had an MRI of the region of concern and are otherwise asymptomatic.\n4. Physical exam at your institution within 1 year prior to consent.\n5. Written informed consent must be obtained from the legal guardians of all participants \\\u003C18 years of age.\n\nExclusion Criteria:\n\n1. Presence of a known, symptomatic PN with or without previous MRI imaging.\n2. Patients who have had previous whole-body MRI (WBMRI) are excluded from the study. However, patients who have had regional MRI(s) for an indication other than a PN and did not have a PN identified on previous MRI may still be eligible for the study.\n3. Inability to undergo MRI and\u002For contraindication for MRI examinations following the MRI protocol.\n4. Prior treatment with selumetinib or another specific MEK1\u002F2 inhibitor.\n5. Evidence of an optic pathway or other low-grade glioma, high grade glioma, malignant peripheral nerve sheath tumor, or other cancer\u002Ftumor requiring treatment with chemotherapy, biologic therapy or radiation therapy.\n6. Ongoing radiation therapy, chemotherapy, hormonal therapy directed at a tumor, immunotherapy, or biologic therapy.\n7. Clinical judgement by the investigator that the patient should not participate in the study.\n\nPART 2:\n\nInclusion Criteria:\n\n1. Enrolled on Part 1 of this study and completed baseline WBMRI within 6 weeks of planned enrollment on Part 2.\n2. A measurable (≥3 mL) PN in a high-risk location as defined below (this must be confirmed by Study Chair or a member of the Study Committee prior to enrollment on Part 2).\n\n   * In the head or neck (with the exception of isolated scalp lesions) OR\n   * Within the brachial or lumbosacral plexus OR\n   * Adjacent to high-risk structure(s), defined as:\n\n     1. Major (\"named\") blood vessel OR\n     2. Major (\"named\") airway OR\n     3. Hollow viscus OR\n     4. Spinal cord and foramina OR\n     5. Vital Organs (including heart, lungs, liver, spleen, etc.)\n3. Body Surface Area (BSA): BSA ≥ 0.55 m2 \\[pending availability of granule formulation\\].\n4. Performance status: Lansky performance ≥70%. Participants who are wheelchair bound because of paralysis or immobility secondary to a non-PN related manifestation of NF1 (such as tibial pseudarthrosis or severe scoliosis) should be considered ambulatory when they are in their wheelchair.\n5. Able to swallow whole capsules \\[Pending availability of granule formulation\\].\n6. Hematologic Function: Absolute neutrophil count ≥1200\u002FµL, hemoglobin ≥9g\u002FdL, and platelets ≥100,000\u002FµL (without transfusions).\n7. Hepatic Function: Bilirubin within 1.5 x the upper limit of normal for age, with the exception of those with Gilbert syndrome, and AST\u002FALT within ≤ 3 x upper limit of normal.\n8. Renal Function: Creatinine clearance or radioisotope GFR ≥60ml\u002Fmin\u002F1.73 m2 or a normal serum creatinine based on age, described in the table below.\n\n   Age (years) Maximum Serum Creatinine (mg\u002FdL)\n\n   ≤5 0.8 \\>5 to ≤10 1.0 \\>10 to ≤15 1.2 \\>15 1.5\n9. Cardiac Function:\n\n   1. Normal ejection fraction (ECHO or cardiac MRI) ≥ 53% (or the institutional normal; if a range is given then the upper value of the range will be used).\n   2. EKG with QTC or QTcF ≤450 msec.\n10. Adequate Blood Pressure defined as:\n\n    A blood pressure (BP) ≤ the 95th percentile for age, height, and gender. Adequate blood pressure can be achieved using medication for treatment of hypertension. Participants must be on stable antihypertensive regimen for at least 30 days prior to study entry.\n11. Willingness to avoid excessive sun exposure and use adequate sunscreen protection if sun exposure is anticipated.\n12. Willingness to avoid the ingestion of grapefruit and Seville oranges (as well as other products containing these fruits, e.g., grapefruit juice or marmalade) during the study, as these may affect selumetinib metabolism.\n\nExclusion Criteria:\n\n1. Evidence of an optic pathway or other low-grade glioma, high-grade glioma, malignant peripheral nerve sheath tumor, or other cancer\u002Ftumor requiring treatment with chemotherapy, biologic therapy or radiation therapy.\n2. Ongoing radiation therapy, chemotherapy, hormonal therapy, immunotherapy, or biologic therapy directed at a tumor.\n3. Prosthesis, orthopedic implant, or dental braces that would interfere with volumetric analysis of target PN on MRI.\n4. Use of an investigational agent within the past 30 days.\n5. Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diatheses, or renal transplant, including any patient known to have hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) will be excluded.\n6. Participants who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.\n7. Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption.\n8. Supplementation with vitamin E greater than 100% of the daily recommended dose. Any multivitamin containing vitamin E must be stopped prior to initiation of therapy.\n9. Participants not achieving adequate blood pressure despite antihypertensive therapy for control of blood pressure.\n10. Cardiac conditions:\n\n    1. Known inherited coronary disease\n    2. Symptomatic heart failure (NYHA Class II-IV prior or current cardiomyopathy, or severe valvular heart disease)\n    3. Prior or current cardiomyopathy\n    4. Severe valvular heart disease\n    5. History of atrial fibrillation\n11. Ophthalmologic conditions:\n\n    1. Current or past history of central serous retinopathy or retinal pigment epithelial detachment (RPED).\n    2. Current or past history of retinal vein occlusion.\n    3. History of radiation therapy that included the orbit in the field of treatment.\n    4. 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.\n    5. Participants with any other significant abnormality on ophthalmic examination should be discussed with the Study Chair for potential eligibility.\n    6. Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) will NOT be considered a significant abnormality for the purposes of the study.\n12. Known severe hypersensitivity to selumetinib or any excipient of selumetinib or history of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib.\n13. Recent major surgery within a minimum of 4 weeks prior to starting study treatment.\n14. Any unresolved chronic toxicity with CTCAE grade ≥ 2 from previous therapy, except for alopecia.\n15. 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\nPART 3:\n\nInclusion Criteria:\n\n1. Enrolled on Part 2 of this study and had PN growth \\>20% OR development of PN related symptom(s) while on observation portion of Part 2 (including the first 2 years for the observation arm OR during first year of observation after treatment with selumetinib).\n2. Body Surface Area (BSA): BSA ≥ 0.55 m2 \\[pending availability of granule formulation\\].\n3. Performance status: Lansky performance ≥70%. Participants who are wheelchair bound because of paralysis or immobility secondary to a non-PN related manifestation of NF1 (such as tibial pseudarthrosis or severe scoliosis) should be considered ambulatory when they are in their wheelchair.\n4. Able to swallow whole capsules \\[Pending availability of granule formulation\\].\n5. Hematologic Function: Absolute neutrophil count ≥1200\u002FµL, hemoglobin ≥9g\u002FdL, and platelets ≥100,000\u002FµL (without transfusions).\n6. Hepatic Function: Bilirubin within 1.5 x the upper limit of normal for age, with the exception of those with Gilbert syndrome, and AST\u002FALT within ≤ 3 x upper limit of normal.\n7. Renal Function: Creatinine clearance or radioisotope GFR ≥60mL\u002Fmin\u002F1.73 m2 or a normal serum creatinine based on age, described in the table below.\n\n   Age (years) Maximum Serum Creatinine (mg\u002FdL)\n\n   ≤5 0.8 \\>5 to ≤10 1.0 \\>10 to ≤15 1.2 \\>15 1.5\n8. Cardiac Function:\n\n   1. Normal ejection fraction (ECHO or cardiac MRI) ≥ 53% (or the institutional normal; if a range is given then the upper value of the range will be used).\n   2. EKG with QTC or QTcF ≤450 msec.\n9. Adequate Blood Pressure defined as:\n\n   A blood pressure (BP) ≤ the 95th percentile for age, height, and gender. Adequate blood pressure can be achieved using medication for treatment of hypertension. Participants must be on stable antihypertensive regimen for at least 30 days prior to study entry.\n10. Willingness to avoid excessive sun exposure and use adequate sunscreen protection if sun exposure is anticipated.\n11. Willingness to avoid the ingestion of grapefruit and Seville oranges (as well as other products containing these fruits, e.g., grapefruit juice or marmalade) during the study, as these may affect selumetinib metabolism.\n\nExclusion Criteria:\n\n1. Evidence of an optic pathway or other low-grade glioma, high-grade glioma, malignant peripheral nerve sheath tumor, or other cancer\u002Ftumor requiring treatment with chemotherapy, biologic therapy or radiation therapy.\n2. Ongoing radiation therapy, chemotherapy, hormonal therapy, immunotherapy, or biologic therapy directed at a tumor.\n3. Prosthesis, orthopedic implant, or dental braces that would interfere with volumetric analysis of target PN on MRI.\n4. Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diatheses, or renal transplant, including any patient known to have hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) will be excluded.\n5. Participants who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.\n6. Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption.\n7. Supplementation with vitamin E greater than 100% of the daily recommended dose. Any multivitamin containing vitamin E must be stopped prior to initiation of therapy.\n8. Participants not achieving adequate blood pressure despite antihypertensive therapy for control of blood pressure.\n9. Cardiac conditions:\n\n   1. Known inherited coronary disease\n   2. Symptomatic heart failure (NYHA Class II-IV prior or current cardiomyopathy, or severe valvular heart disease)\n   3. Prior or current cardiomyopathy\n   4. Severe valvular heart disease\n   5. History of atrial fibrillation\n10. Ophthalmologic conditions:\n\n    1. Current or past history of central serous retinopathy or retinal pigment epithelial detachment (RPED).\n    2. Current or past history of retinal vein occlusion.\n    3. History of radiation therapy that included the orbit in the field of treatment.\n    4. 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.\n    5. Participants with any other significant abnormality on ophthalmic examination should be discussed with the Study Chair for potential eligibility.\n    6. Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) will NOT be considered a significant abnormality for the purposes of the study.\n11. Known severe hypersensitivity to selumetinib or any excipient of selumetinib or history of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib.\n12. Recent major surgery within a minimum of 4 weeks prior to starting study treatment.\n13. Any unresolved chronic toxicity with CTC AE grade ≥ 2 from previous therapy, except for alopecia.\n14. 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.","ALL","1 Year","8 Years",{"count":21,"type":22},200,"ESTIMATED","INTERVENTIONAL",[25],"PHASE2","Plexiform neurofibromas (PN) are known to cause significant morbidity in children with NF1. The recent FDA approval for selumetinib in children 2 years and older with inoperable symptomatic PN was based on the finding that selumetinib shrinks the majority of PN in children with NF1 and results in clinically meaningful benefit such as improvement in pain or range of motion. However, many morbidities, such as blindness or nerve damage, cannot be fully reversed with PN shrinkage. Therefore, there remains a critical need in this patient population to determine if young participants with PN in high-risk locations may benefit from early medical intervention prior to the development of clinical problems. This study will determine whether participants with asymptomatic PN in high-risk locations can potentially benefit from early treatment with selumetinib.",[28,29],"Neurofibromatosis 1","Plexiform Neurofibroma","RECRUITING","2026-05-26",{"date":33,"type":34},"2026-05-29","ACTUAL",{"date":36,"type":34},"2025-08-27",{"date":38,"type":22},"2032-09-01",{"name":40,"class":41},"University of Alabama at Birmingham","OTHER",15,{"id":44,"slug":45,"hasResults":11,"nctId":46,"briefTitle":47,"officialTitle":48,"acronym":4,"eligibilityCriteria":49,"healthyVolunteers":11,"sex":17,"minAge":50,"maxAge":4,"enrollmentInfo":51,"targetDuration":4,"studyType":23,"phases":53,"briefSummary":55,"conditions":56,"keywords":4,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":57,"lastUpdatePostDateStruct":58,"startDateStruct":60,"completionDateStruct":62,"leadSponsor":64,"locationsCount":67},"100624297","phase-3-evaluation-of-tq-b3234-capsules-in-patients-with-symptomatic-non-surgical-type-1-neurofibromatosis-associated-plexiform-neurofibromas-100624297","NCT07407803","Evaluation of TQ-B3234 Capsules in Patients With Symptomatic, Non-Surgical Type 1 Neurofibromatosis-Associated Plexiform Neurofibromas","Randomized, Double-Blind, Parallel-Controlled, Multicenter Phase III Clinical Trial Evaluating the Efficacy and Safety of TQ-B3234 Capsules Versus Placebo in Patients With Symptomatic, Non-Surgical Type 1 Neurofibromatosis-Associated Plexiform Neurofibromas","Inclusion Criteria:\n\n* The subject voluntarily joins this study, signs the informed consent form, and demonstrates good compliance.\n* Age ≥18 years (calculated from the date of signing the informed consent form).\n* Diagnosis of symptomatic, non-resectable neurofibromatosis type 1 (NF1)-associated plexiform neurofibroma (PN) requiring systemic therapy per investigator judgment.\n* At least one measurable lesion with a dimension ≥3 cm.\n* There should be no significant changes in the use of chronic neuropathic pain medications within 28 days prior to study enrollment.\n* Eastern Cooperative Oncology Group (ECOG) performance status 0-1.\n* Laboratory tests meet the protocol criteria.\n* Women of childbearing potential must agree to use effective contraception during the study and for 6 months after study completion. A negative serum pregnancy test must be documented within 7 days prior to study enrollment. Men must agree to use effective contraception during the study and for 6 months after study completion.\n\nExclusion Criteria:\n\n* Confirmed or suspected malignant glioma or malignant peripheral nerve sheath tumor (MPNST) (excluding low-grade glioma, optic nerve glioma not requiring systemic therapy or radiotherapy); histological confirmation may be required.\n* History of or concurrent other malignancies within 5 years prior to first dosing.\n* Multiple factors affecting oral drug absorption (e.g., dysphagia, chronic diarrhea, intestinal obstruction, major bowel resection).\n* Adverse reactions from prior anti-tumor therapy not recovered to NCI CTCAE v6.0 grade ≤1, except grade 2 alopecia, grade 2 peripheral neuropathy, grade 2 anemia, non-clinically significant and asymptomatic laboratory abnormalities, and hypothyroidism stabilized by hormone replacement therapy.\n* Major surgery, significant traumatic injury, or planned major surgery during the study within 4 weeks prior to first dosing; or presence of long-term non-healed wounds or fractures.\n* History of arterial\u002Fvenous thrombotic events (e.g., cerebrovascular accident including transient ischemic attack (TIA), deep vein thrombosis, pulmonary embolism) or other severe thromboembolic events within 6 months prior to first dosing.\n* Active viral hepatitis with poor control.\n* Active syphilis requiring treatment.\n* Active tuberculosis, idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonia, radiation pneumonitis requiring treatment, or clinically symptomatic active pneumonia.\n* History of substance abuse that cannot be controlled or presence of psychiatric disorders.\n* Planned or prior allogeneic bone marrow or solid organ transplantation.\n* History of hepatic encephalopathy.\n* History of or current retinal vein occlusion (RVO), retinal pigment epithelial detachment (RPED), central serous retinopathy (CSR), glaucoma, or other significant ocular abnormalities (e.g., intraocular pressure \\>21mmHg).\n* Inability to undergo MRI and\u002For presence of MRI contraindications.\n* Major cardiovascular disease.\n* Active or uncontrolled severe infection.\n* Renal failure requiring hemodialysis or peritoneal dialysis.\n* History of immunodeficiency, including HIV-positive or other acquired\u002Fcongenital immunodeficiency diseases.\n* History of epilepsy.\n* Tumor-related symptoms and treatment.\n* Known hypersensitivity to study drug excipients.\n* Participation in and use of other PN clinical trial drugs within 4 weeks prior to first dosing.\n* Pregnant or lactating participants.\n* Any other condition that, in the investigator's judgment, poses a serious risk to participant safety or interferes with study completion.","18 Years",{"count":52,"type":22},177,[54],"PHASE3","This study aims to demonstrate that in subjects with symptomatic, inoperable plexiform neurofibromas associated with neurofibromatosis type 1, TQ-B3234 capsules significantly improve the objective response rate at Week 24 compared to placebo.",[29],"2026-05-22",{"date":59,"type":34},"2026-05-27",{"date":61,"type":34},"2026-03-31",{"date":63,"type":22},"2028-12",{"name":65,"class":66},"Chia Tai Tianqing Pharmaceutical Group Co., Ltd.","INDUSTRY",29,{"id":69,"slug":70,"hasResults":11,"nctId":71,"briefTitle":72,"officialTitle":73,"acronym":74,"eligibilityCriteria":75,"healthyVolunteers":11,"sex":17,"minAge":76,"maxAge":4,"enrollmentInfo":77,"targetDuration":4,"studyType":23,"phases":79,"briefSummary":81,"conditions":82,"keywords":83,"overallStatus":86,"whyStopped":4,"lastUpdateSubmitDate":87,"lastUpdatePostDateStruct":88,"startDateStruct":90,"completionDateStruct":92,"leadSponsor":94,"locationsCount":96},"100554675","phase-1-study-of-cabozantinib-with-selumetinib-for-plexiform-neurofibromas-100554675","NCT06502171","Study of Cabozantinib With Selumetinib for Plexiform Neurofibromas","A Phase 1\u002F1b\u002F2 Study of Cabozantinib in Combination With Selumetinib for Plexiform Neurofibroma in Adults and Adolescents With Neurofibromatosis Type 1","NF113","1.0 INCLUSION CRITERIA\n\n1.1. All participants must have a diagnosis of NF1 based on the 2021 revised consensus criteria.\n\n1.2. Participants must have PN(s) that are progressive OR are causing significant morbidity, such as (but not limited to) head and neck lesions that are compromising the airway or great vessels, brachial or lumbar plexus lesions that are causing nerve compression and loss of function, lesions causing significant disfigurement (e.g., orbital lesions), lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions. Participants with paraspinal PN will be eligible for this trial. Histologic confirmation of tumor is not necessary but should be considered if there are clinical or radiographic findings concerning for malignant transformation of a PN.\n\n1.2.1. For participants enrolled for tumor progression, progression is defined as: Presence of new PN on MRI or CT (documented by comparison with prior MRI or CT), OR A measurable increase in PN size (≥ 20% increase in the volume, or a ≥ 13% increase in the product of the two longest perpendicular diameters, or a ≥ 6% increase in the longest diameter) documented by comparison of two scans (MRI or CT) in the time period of 18 months or less prior to evaluation for this study.\n\n1.2.2. For participants enrolled for tumors causing \"significant disfigurement\" without meeting another criterion (i.e., not progressive or causing other significant morbidity), eligible tumors will be limited to tumors of the head \\& neck or those on other areas of the body that are unable to be concealed by standard garments. In order to enroll a participant with PN for these indications, photographs must be reviewed by a Study Chair and\u002For Co-Chair for decision regarding participant eligibility prior to enrollment.\n\n1.3. Disease status: Measurable disease: Participants must have measurable PN(s) amenable to volumetric MRI analysis. For the purpose of this study, the target lesion must be seen on at least 3 consecutive MRI slices and the field of view must contain the entire tumor of interest. Tumors must be at least 3 mL in volume (most PN 3 cm in longest diameter will meet this criteria). If the tumor is \\\u003C3 cm in longest diameter, the participant may still be eligible. Central review of the MRI of the target PN is required prior to enrollment to ensure that the tumor is measurable and amenable to volumetric analysis.\n\n1.4. Age: Participants must be ≥16 years of age at the time of study entry.\n\n1.5. Performance Level: Participants must have Karnofsky ³ 50%. Note: Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for assessing the performance score.\n\n1.6. Body Surface Area (BSA): Participants must have a BSA of 1.0 m2 or greater.\n\n1.7. Organ Function Requirements:\n\n1.7.1. Adequate Bone Marrow Function Defined as: Absolute neutrophil count (ANC) ≥ 1500\u002FµL without granulocyte colony-stimulating factor support.\n\nWhite blood cell count ≥ 2500\u002FµL Platelet count ³ 100,000\u002FmL without transfusion Hemoglobin ³10.0 gm\u002FdL (\\>5 days between enrollment and last RBC transfusion)\n\n1.7.2. Adequate Renal Function Defined as: Maximum serum creatinine based on age\u002Fgender as per institutional standards OR a creatinine clearance, radioisotope GFR, or calculated creatinine clearance using the Cockcroft-Gault equation ³70ml\u002Fmin\u002F1.73 m2.\n\nCockcroft-Gault equation:\n\n* Males: (140 - age) x weight (kg)\u002F(serum creatinine \\[mg\u002FdL\\] × 72)\n* Females: \\[(140 - age) x weight (kg)\u002F(serum creatinine \\[mg\u002FdL\\] × 72)\\] × 0.85 Urine protein\u002Fcreatinine ratio (UPCR) ≤ 1 mg\u002Fmg (≤ 113.2 mg\u002Fmmol), or 24-h urine protein ≤ 1 g.\n\n1.7.3. Adequate Liver Function Defined as: Total bilirubin (sum of conjugated + unconjugated) £ 1.5x upper limit of normal (ULN) for age (for participants with Gilbert's disease ≤3x ULN), and Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) \\\u003C 2.5x the upper limit of normal (ULN).\n\nSerum albumin ³ 2.8 g\u002FdL. PT\u002FINR and partial thromboplastin time (PTT) test \\\u003C 1.3x the laboratory ULN\n\n1.7.4. Adequate Thyroid Function Defined as: ≤ Grade 1 or adequately managed asymptomatic Grade 2 hypothyroidism.\n\n1.7.5. CPK level within normal limits within 14 days from the start of treatment.\n\n1.7.6. Normal pancreatic function: amylase and lipase levels ≤ 1.5 x ULN\n\n1.7.7. 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\nIn adolescents, a blood pressure (BP) ≤ 90th percentile for age, height, and sex.\n\nIn adults (³18 years of age), a systolic blood pressure ≤130 mmHg and a diastolic pressure of ≤80 mmHg.\n\n1.8. Major surgery: Only participants who are not anticipated to need major surgery within 3 months after enrollment are eligible.\n\n1.9. Sexually active fertile participants and their partners must agree to use 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 4 months 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 7 days prior to first dose of study treatment and must have a negative urine or serum pregnancy test.\n\n1.10. 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). Participants or legal guardians must be capable of understanding and complying with the protocol requirements and must have signed the informed consent document. Participants unable to provide informed consent\u002Fassent will NOT be enrolled on this study.\n\n1.11. Willingness to avoid excessive sun exposure and use adequate sunscreen protection if sun exposure is anticipated.\n\n1.12. Willingness to avoid the ingestion of grapefruit and Seville oranges (as well as other products containing these fruits, e.g., grapefruit juice or marmalade) during the study, as these may affect selumetinib metabolism.\n\n2.0 EXCLUSION CRITERIA\n\n2.1. Evidence of an optic pathway or other low-grade glioma, high-grade glioma, malignant peripheral nerve sheath tumor, or other cancer\u002Ftumor requiring treatment with chemotherapy, biologic therapy or radiation therapy.\n\n2.2. Patients with high-grade glioma, atypical or malignant peripheral nerve sheath tumor, or other malignancy who received treatment in the last 12 months. Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that have undergone potentially curative therapy.\n\n2.3. Dental braces or prosthesis that interfere with volumetric analysis of the neurofibroma(s).\n\n2.4. Prior Therapy: Participants may have received treatment for a PN or other tumor\u002Fmalignancy but must have fully recovered to baseline or CTCAE ≤ Grade 1 from acute toxicities from prior therapies except alopecia.\n\nMyelosuppressive chemotherapy: Must not have received within 28 days of entry onto this study.\n\n2.5. Hematopoietic growth factors: Must not have received a growth factor that supports platelet, red or white cell number or function within 14 days of initiation of therapy.\n\n2.6. Biologic (anti-neoplastic agent): At least 28 days (or 5 half-lives whichever is longer) since the completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 28 days after administration (or 5 half-lives whichever is longer), this period must be extended beyond the time during which adverse events are known to occur. These participants must be discussed with the Study Chair on a case-by-case basis.\n\n2.7. Investigational Drugs: At least 28 days (or 5 half-lives whichever is longer) since the completion of therapy with an investigational drug or systemic anticancer treatment. For agents that have known adverse events occurring beyond 28 days after administration (or 5 half-lives whichever is longer), this period must be extended beyond the time during which adverse events are known to occur. These participants must be discussed with the Study Chair on a case-by-case basis.\n\n\\- Prior treatment with cabozantinib or selumetinib is permitted for participants on Phase 1 of this study only (not Phase 1b\u002F2). Participants may have previously received cabozantinib and\u002For a MEK inhibitor but not simultaneously. If participants have received either cabozantinib or selumetinib previously, they must have tolerated either medication at the recommended entry doses for this study or greater and must not have discontinued therapy due to toxicity. Participants who have received the combination of cabozantinib with any MEK inhibitor previously will not be eligible. Prior treatment with cabozantinib and\u002For selumetinib will not be permitted for participants on Phase 1b or Phase 2.\n\n2.8. Radiation therapy: 6 months from involved field radiation to index PN(s) must have elapsed prior to study entry; ³ 6 weeks must have elapsed if participant has received radiation to areas outside index PN(s) Participants who received radiation to the orbit at any time previously are not eligible.\n\n\\>12 weeks must have elapsed between systemic treatment with radionuclides and first dose of study treatment.\n\nParticipants with clinically relevant ongoing complications from prior radiation therapy are not eligible.\n\n2.9. Surgery:\n\n2.9.1. Participants are not eligible if complete resection of a PN with acceptable morbidity is feasible, or if a participant with a feasible surgical option with minimal risk for surgical morbidity refuses surgery. Participants who underwent surgery for a progressive PN will be eligible to enter the study after the surgery, provided the PN was incompletely resected and is measurable.\n\n2.9.2. Any major surgery within 3 months before first dose of study treatment.\n\n2.9.3. Any minor surgeries (e.g., the placement of an implanted vascular device, tooth extractions, biopsy, or an invasive operative procedure for procurement of tissue samples or body fluids using a needle or trocar, other than routine peripheral venous access) within 1 month before first dose of study treatment.\n\n2.9.4. Participants must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Participants with clinically relevant ongoing complications from prior surgery are not eligible.\n\n2.10. Concomitant anticoagulation with coumarin agents (e.g., warfarin), low molecular weight heparins, direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following: Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines)\n\n2.11. Clinically significant hematuria, hematemesis, or hemoptysis of \\>0.5 teaspoon (2.5ml) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before first dose of study treatment.\n\n2.12. Known cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.\n\n2.13. Cardiovascular disorders: 2.13.1. Congestive heart failure New York Heart Association Class 2-4, unstable angina pectoris (Canadian Cardiovascular Society grade II-IV despite medical therapy), prior or current cardiomyopathy, or severe valvular heart disease, baseline left ventricular ejection fraction (LVEF) below the LLN or \\\u003C55% measured by echocardiography or institution's LLN for MUGA, serious cardiac arrhythmias including atrial fibrillation.\n\n2.13.2. Stroke (including transient ischemic attack \\[TIA\\]), acute coronary syndrome or myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose of study treatment.\n\n2.13.3. Participants with a diagnosis of incidental, subsegmental PE or DVT within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation (aspirin) for at least 1 week before first dose of study treatment.\n\n2.13.4. Baseline QTc interval \\>450 msec\n\n2.14. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:\n\n2.14.1. The participant has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.\n\n2.14.2. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment.\n\nNote: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment.\n\n2.15. Ophthalmologic conditions:\n\n2.15.1. Current or history of central serous retinopathy\n\n2.15.2. Current or history of retinal vein occlusion\n\n2.15.3. 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\n2.15.4. Participants with any other significant abnormality on ophthalmic examination should be discussed with the Study Chair for potential eligibility.\n\n2.15.5. 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\n2.16. Other clinically significant disorders that would preclude safe study participation, including:\n\n2.16.1. Serious non-healing wound, ulcer, or bone fracture.\n\n2.16.2. Uncompensated\u002Fsymptomatic hypothyroidism.\n\n2.16.3. Moderate to severe hepatic impairment (Child-Pugh B or C).\n\n2.16.4. Active infection\n\n2.16.5. A known history of HIV seropositivity or known immunodeficiency. HIV testing will not be required as part of this trial, unless HIV is clinically suspected.\n\n2.16.6. Uncontrolled diabetes, severe malnutrition, chronic liver or renal disease\n\n2.16.7. History of organ transplant\n\n2.17. Pregnant or lactating women.\n\n2.18. Inability to swallow tablets.\n\n2.19. Previously identified allergy or hypersensitivity to components of the study treatment formulations.\n\n2.20. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of cabozantinib or selumetinib (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).\n\n2.21. Participants who require chronic concomitant treatment of moderate\u002Fstrong CYP3A4 inducers or inhibitors (Appendix XIII). While not an exclusion criterion, unless clinically indicated, participants should avoid taking other additional non-study medications that may interfere with the study medications. Participants should avoid medications that are known to either induce or inhibit the activity of hepatic microsomal isoenzymes CYP1A2, and CYP2C19, as this may interfere with the metabolism of selumetinib (Appendix XIII).\n\n2.22. Participants with a history of significant noncompliance to medical regimens, are unwilling to or unable to comply with the protocol, or who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.","16 Years",{"count":78,"type":22},30,[80],"PHASE1","Based on the clinical activity of both selumetinib and cabozantinib as monotherapies in clinical trials, the demonstrated activity of these agents in reduced doses in preclinical studies, and the non-overlapping toxicity profiles, the study will assess the tolerability and efficacy of selumetinib and cabozantinib in combination in participants with NF1 ≥16 years old with progressive and\u002For symptomatic PN in a phase 1\u002F1b\u002F2 clinical trial.\n\nTrial Design Phase 1 This will be an open label, dose escalation phase. Dose level escalation will be determined by a rolling six design. In this design, up to 6 participants can be enrolled at a given dose level and then evaluated for dose limiting toxicity (DLT) within the DLT window. The DLT window is defined as 16 weeks in this study based on the long half-life of cabozantinib and the desire to have maximum confidence about long-term tolerability of the combination prior to proceeding to the next dose level.\n\nPhase 1b Once the recommended phase 2 dose has been determined in phase 1, an expanded cohort of 12 participants will be enrolled in phase 1b portion of the study.\n\nPhase 2 This will be an open label, single-arm phase using the recommended phase 2 dose.",[28,29],[84,85],"adolescents","adults","NOT_YET_RECRUITING","2026-03-10",{"date":89,"type":34},"2026-03-12",{"date":91,"type":22},"2026-08-01",{"date":93,"type":22},"2034-08-01",{"name":95,"class":41},"Girish Dhall, MD",1,{"id":98,"slug":99,"hasResults":11,"nctId":100,"briefTitle":101,"officialTitle":102,"acronym":103,"eligibilityCriteria":104,"healthyVolunteers":11,"sex":17,"minAge":50,"maxAge":4,"enrollmentInfo":105,"targetDuration":4,"studyType":107,"phases":4,"briefSummary":108,"conditions":109,"keywords":115,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":119,"lastUpdatePostDateStruct":120,"startDateStruct":122,"completionDateStruct":124,"leadSponsor":126,"locationsCount":96},"100555728","neurofibromatosis-type-1-tumor-early-detection-study-100555728","NCT06515860","Neurofibromatosis Type 1 Tumor Early Detection Study","Observational Trial of Liquid Biopsy for Malignant Peripheral Nerve Sheath Tumor (MPNST) Among Participants With Neurofibromatosis Type 1","NF1-TED","Inclusion Criteria:\n\n* 18 years and older (adults only)\n* Neurofibromatosis Type 1 (NF1) diagnosis (2021 Revised Diagnostic Criteria, PMID: 34012067)\n* History of plexiform neurofibroma (PN)\n* Able to read and understand English or Spanish\n* Live in the USA\n\nExclusion Criteria:\n\n* Are children (younger than 18 years old)\n* Do not have NF1\n* Have no evidence of PN\n* Are not able to read and understand English or Spanish",{"count":106,"type":22},1000,"OBSERVATIONAL","The goal of this observational study is to determine if a liquid biopsy (i.e. blood test) is an effective clinical tool for monitoring the development of malignant peripheral nerve sheath tumor (MPNST) among adults (18 years and older) with Neurofibromatosis Type 1 (NF1), compared to the current standard of care. The main questions it aims to answer are:\n\nHow effective is liquid biopsy compared to the current standard of care (clinical surveillance and imaging) for early detection of MPNST development among people with NF1? Can liquid biopsy offer a cost-effective method for early detection of MPNST in people with NF1? Also, can liquid biopsy provide earlier detection that potentially leads to better outcomes? Also, can offering liquid biopsy improve access to care for people experiencing barriers to access (such as minority populations or people in rural areas)?\n\nAt baseline, participants will be asked to:\n\n* Complete surveys to provide their demographic and NF1-related health information.\n* Report whether or not they are experiencing MPNST-related symptoms.\n* Provide blood samples (15 mL blood total between three tubes, which is approximately one tablespoon).\n\nEvery six months during the five-year follow-up period, participants will be asked to:\n\n* Complete additional surveys to report whether or not they are experiencing MPNST-related symptoms and\u002For if they have been diagnosed with a new MPNST.\n* Provide an additional blood sample (10 mL blood total in one tube).\n\nIf diagnosed with an MPNST by their healthcare provider during the follow-up period, participants will be asked to:\n\n* Complete an additional survey regarding their diagnosis and symptoms.\n* Provide an additional blood sample (10 mL blood in one tube).\n* In parallel, the study team will request a sample of tumor tissue from the care provider, if available.",[110,28,29,111,112,113,114],"Neurofibromatosis Type 1","Plexiform Neurofibromas","Malignant Peripheral Nerve Sheath Tumor","Malignant Peripheral Nerve Sheath Tumors","Atypical Neurofibroma",[116,117,118],"Liquid biopsy","Cancer surveillance","Tumor early detection","2026-01-08",{"date":121,"type":34},"2026-01-09",{"date":123,"type":34},"2024-08-07",{"date":125,"type":22},"2030-07",{"name":127,"class":41},"David Miller",{"id":129,"slug":130,"hasResults":11,"nctId":131,"briefTitle":132,"officialTitle":133,"acronym":4,"eligibilityCriteria":134,"healthyVolunteers":11,"sex":17,"minAge":135,"maxAge":136,"enrollmentInfo":137,"targetDuration":4,"studyType":23,"phases":139,"briefSummary":140,"conditions":141,"keywords":4,"overallStatus":86,"whyStopped":4,"lastUpdateSubmitDate":143,"lastUpdatePostDateStruct":144,"startDateStruct":146,"completionDateStruct":148,"leadSponsor":150,"locationsCount":96},"100594818","phase-1-follow-up-study-to-evaluate-the-safety-and-efficacy-of-fcn-159-in-pediatric-participants-with-neurofibromatosis-type-1-100594818","NCT07024394","Follow-up Study to Evaluate the Safety and Efficacy of FCN-159 in Pediatric Participants With Neurofibromatosis Type 1","A Long-term Follow-up Study to Evaluate the Safety and Efficacy of Ruvometinib Tablets (FCN-159 Tablets) in Pediatric Participants With Neurofibromatosis Type 1","Inclusion Criteria:\n\nPatients from the pediatric cohort of the FCN-159-002 study. Willing to participate in the long-term follow-up study and capable of understanding and voluntarily signing the informed consent form.\n\nExclusion Criteria:\n\nAny clinically significant condition that, in the investigator's judgment, may interfere with study participation or compliance with safety requirements.\n\nPatients unable to comply with visit-related requirements.","2 Years","20 Years",{"count":138,"type":22},65,[80,25],"FCN-159 (Luvometinib Tablets), an orally available and highly potent selective inhibitor of MEK1\u002F2,demonstrated good tolerability and exhibited notable anti-tumor activity in pediatric pts with NF1-related PN in study NCT04954001.This study is a 5-year long-term follow-up of the FCN-159-002 study, involving all enrolled patients to further assess safety, growth and development effects, and treatment efficacy.",[28,29,142],"NF1","2025-06-09",{"date":145,"type":34},"2025-06-17",{"date":147,"type":22},"2025-06-12",{"date":149,"type":22},"2029-09-23",{"name":151,"class":66},"Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd."]