[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100433361":3},{"organization":4,"armGroups":7,"interventions":30,"overallOfficials":38,"centralContacts":44,"locations":51,"responsibleParty":69,"collaborators":71,"id":75,"slug":76,"hasResults":77,"nctId":78,"briefTitle":79,"officialTitle":80,"acronym":49,"eligibilityCriteria":81,"healthyVolunteers":77,"sex":82,"minAge":83,"maxAge":84,"enrollmentInfo":85,"targetDuration":49,"studyType":88,"phases":89,"briefSummary":92,"conditions":93,"keywords":97,"overallStatus":53,"whyStopped":49,"lastUpdateSubmitDate":128,"lastUpdatePostDateStruct":129,"startDateStruct":132,"completionDateStruct":134,"leadSponsor":136,"locationsCount":137},{"fullName":5,"class":6},"St. Jude Children's Research Hospital","OTHER",[8,14,18,22,26],{"label":9,"type":10,"description":11,"interventionNames":12},"Phase I: Recurrent and\u002For progressive low-grade glioma without prior exposure to MEK inhibitors","EXPERIMENTAL","Participants will receive mirdametinib at one of the dose levels twice daily days 1-28. For the first cycle of treatment, participants will take mirdametinib tablets dissolved in water. After the first cycle of treatment, participants may receive the medicine the same way (dissolved in water) or may receive capsules. Treatment repeats every 28 days for up to 26 cycles of treatment (24 months) in the absence of disease progression or unacceptable toxicity.",[13],"Drug: Mirdametinib",{"label":15,"type":10,"description":16,"interventionNames":17},"Phase 2, Cohort 1: Newly diagnosed and\u002For previously untreated (except surgery)","Participants will receive the RP2D of mirdametinib. Therapy will be administered in cycles of 28 days and may be continued for up to 24 months (26 cycles) in absence of disease progression or unacceptable toxicity.",[13],{"label":19,"type":10,"description":20,"interventionNames":21},"Phase 2, Cohort 2: Recurrent and\u002For Progressive without prior exposure to MEK inhibitors","Participants will receive the RP2D of mirdametinib. Participants may take mirdametinib tablets dissolved in water, or receive capsules. Therapy will be administered in cycles of 28 days and may be continued for up to 24 months (26 cycles) in absence of disease progression or unacceptable toxicity.",[13],{"label":23,"type":10,"description":24,"interventionNames":25},"Phase 2, Cohort 3a:","Participants with recurrent and\u002For progressive low-grade glioma who previously received ≥ 6 courses MEK inhibitor (including mirdametinib) and did not progress while on active MEKi therapy. Participants will receive the RP2D of mirdametinib. Participants with previous exposure to mirdametinib may receive a starting dose lower than the RP2D, depending on the dose they tolerated during their previous exposure. Participants may take mirdametinib tablets dissolved in water, or receive capsules. Therapy will be administered in cycles of 28 days and may be continued for up to 24 months (26 cycles) in absence of disease progression or unacceptable toxicity.",[13],{"label":27,"type":10,"description":28,"interventionNames":29},"Phase 2, Cohort 3b:","Participants with recurrent and\u002For progressive low-grade glioma who previously received ≥ 6 courses MEK inhibitor (including mirdametinib) and did not progress while on active MEKi therapy. Participants will receive the RP2D of mirdametinib. Participants may take mirdametinib tablets dissolved in water, or receive capsules. Therapy will be administered in cycles of 28 days and may be continued for up to 24 months (26 cycles) in absence of disease progression or unacceptable toxicity.",[13],[31],{"type":32,"name":33,"description":34,"armGroupLabels":35,"otherNames":36},"DRUG","Mirdametinib","By mouth, nasogastric (NG) tube or gastrostomy tube (G-tube) BID, days 1-28",[15,19,23,27,9],[37],"PD-0325901",[39,42],{"name":40,"affiliation":5,"role":41},"Giles W. Robinson, MD","PRINCIPAL_INVESTIGATOR",{"name":43,"affiliation":5,"role":41},"Anna Vinitsky, MD, MS",[45],{"name":46,"role":47,"phone":48,"phoneExt":49,"email":50},"Tabatha E. Doyle, RN","CONTACT","901-595-2544",null,"tabatha.doyle@stjude.org",[52],{"facility":5,"status":53,"city":54,"state":55,"zip":56,"country":57,"countryCode":58,"cosmosGeoPoint":59,"geoPoint":64,"contacts":65},"RECRUITING","Memphis","Tennessee","38105","United States","US",{"type":60,"coordinates":61},"Point",[62,63],-90.04898,35.14953,{"lat":63,"lon":62},[66,67,68],{"name":46,"role":47,"phone":48,"phoneExt":49,"email":50},{"name":40,"role":41,"phone":49,"phoneExt":49,"email":49},{"name":43,"role":41,"phone":49,"phoneExt":49,"email":49},{"type":70,"investigatorFullName":49,"investigatorTitle":49,"investigatorAffiliation":49,"oldNameTitle":49,"oldOrganization":49},"SPONSOR",[72],{"name":73,"class":74},"SpringWorks Therapeutics, Inc.","INDUSTRY","100433361","phase-1-sj901-evaluation-of-mirdametinib-in-children-adolescents-and-young-adults-with-low-grade-glioma-100433361",false,"NCT04923126","SJ901: Evaluation of Mirdametinib in Children, Adolescents, and Young Adults With Low-Grade Glioma","SJ901: Phase 1\u002F2 Evaluation of Single Agent Mirdametinib (PD-0325901), a Brain-Penetrant MEK1\u002F2 Inhibitor, for the Treatment of Children, Adolescents, and Young Adults With Low-Grade Glioma","Inclusion Criteria: Screening Phase\n\n* Participants with histologically confirmed or suspected low-grade glioma, including neuronal and mixed neuronal-glial tumors\n* Participant must have adequate tumor tissue from primary and\u002For relapsed tumor for central pathology review\n* For Phase 1: Projected to be ≥ 2 years and \\\u003C 25 years at the time of study enrollment\n* Participant's body surface area (BSA) at time of study enrollment must fall within the range outlined in the protocol for the specific dose level under evaluation:\n\n  * Phase 1: Dose Finding\u002FDose-escalation\n\n    * For Phase 1 participant's BSA must fall within the range specified in the protocol for the specific dose level under evaluation.\n  * Phase 2: All Cohorts:\n\n    * For Phase 2 of the study the upper BSA restrictions will be removed.\n* Participant and\u002For guardian can understand and is willing to sign a written informed consent document according to institutional guidelines\n\nExclusion Criteria: Screening Phase\n\n* Participants with known current retinal pathology that is consistent with or a precursor for central serous retinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration\n* Participants with a known malabsorption syndrome or preexisting gastrointestinal conditions that may impair absorption of mirdametinib (e.g., gastric bypass, lap band, or other gastric procedures)\n* Participant with a known history of liver disease or known hepatic or biliary abnormalities (except for Gilbert's syndrome or asymptomatic gallstones)\n* Participants with a clinically significant history of chronic interstitial lung disease (such as bronchopulmonary dysplasia, chronic bronchiolitis, obliterative bronchiolitis, chronic aspiration pneumonia, surfactant protein disorder, or other serious chronic pulmonary condition). Participants with a history of asthma, reactive airways disease, or viral pneumonitis are not to be excluded if disease has resolved or is well-controlled.\n\nInclusion Criteria: Phase 1 and Phase 2, All Cohorts\n\n* Participant must be ≥ 2 years and \\\u003C 25 years of age at the time of enrollment\n* Participant's BSA at time of study enrollment must fall within the range outlined below for the specific dose level under evaluation:\n\n  * Phase 1: Dose-finding\u002FDose-escalation\n\n    * For Phase 1 participant's BSA must fall within the range specified in the protocol for the specific dose level under evaluation.\n  * Phase 2: All Cohorts\n\n    * For Phase 2 of the study the upper BSA restrictions will be removed.\n* Participant must have confirmation of one of the following diagnosis per St. Jude Children's Research Hospital central pathology review of primary and\u002For relapsed tumor:\n\n  * Eligible tumors include:\n\n    * Low-grade glioma\u002Fastrocytic tumor\u002Fglioneuronal tumor\u002Fneuroepithelial tumor, not otherwise specified (NOS) or not elsewhere classified (NEC)\n    * Pilocytic astrocytoma\n    * Pilomyxoid astrocytoma\n    * Pleomorphic xanthroastrocytoma\n    * Ganglioglioma\n    * Gangliocytoma\n    * Diffuse glioma, diffuse astrocytoma, oligodendroglioma, or oligoastrocytoma\n    * Papillary glioneuronal tumor\n    * Rosette-forming glioneuronal tumor\n    * Diffuse leptomeningeal glioneuronal tumor\n    * Central neurocytoma, extraventricular neurocytoma\n    * Angiocentric glioma\n    * Dysembryoplastic neuroepithelial tumor (DNET), septal DNET, myxoid glioneuronal tumor\n    * Tectal glioma\n    * Desmoplastic infantile astrocytoma \u002F ganglioglioma\n    * Polymorphous low-grade neuroepithelial tumor of the young\n    * Multinodular and vacuolating neuronal tumor\n* In addition, tumor on central review must show evidence supporting MAPK pathway activation as defined by IHC, FISH and\u002For DNA\u002FRNA sequencing (i.e. BRAF fused or rearranged, FGFR1\u002F2\u002F3 aberration, NF1, NF2, PTPN11, SOS1, RAF1 mutations, MYB or MYBL1 fused or rearranged, etc.) or occur in a participant with known NF1, NF2, SOS1, RAF1, or PTPN11 germline mutation. (Note: tests that show evidence supporting MAPK pathway activation that have been already performed do not need to be repeated as long as deemed acceptable by central review).\n* Participant must have measurable or evaluable disease (as defined in the protocol)\n\n  * Note: Participants with metastatic disease or multiple independent primary LGGs are allowed on study.\n* Participants who are receiving corticosteroids must be on a stable or decreasing dose for at least 1 week prior to enrollment with no plans for escalation.\n* Participant must have a Lansky (\\\u003C16 years) or Karnofsky (≥16 years) performance score of ≥ 50 and, in the opinion of the investigator, a minimum life expectancy of at least 6 weeks.\n\n  * Note: Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n* Participant must have adequate bone marrow and organ function as defined as:\n\n  * ANC ≥ 1.0 x 10\\^9\u002FL without growth factor support within 7 days\n  * Platelet count ≥ 75x 10\\^9\u002FL without support of a platelet transfusion within 7 days\n  * Hemoglobin ≥8.0 g\u002FdL without support of a blood transfusion within 7 days\n  * Potassium, total calcium (corrected for serum albumin), magnesium, sodium and phosphorus must be ≤ grade 1 or corrected to ≤ grade 1 with supplements before first dose of study medication\n  * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN. For the purposes of this study the ULN of ALT and AST is 45 U\u002FL.\n  * Total bilirubin ≤ ULN; or if \\> ULN then direct bilirubin ≤ 1.5 x ULN\n* Adequate renal function defined as:\n\n  * Serum creatinine ≤ the maximum serum creatinine based on age\u002Fgender: Age: 2 to \\\u003C 6 years: maximum serum creatinine (mg\u002FdL) 0.8 (male, female), Age: 6 to \\\u003C10 years: maximum serum creatinine (mg\u002FdL) 1 (male, female), Age: 10 to \\\u003C13 years: maximum serum creatinine (mg\u002FdL) 1.2 (male, female), Age: 13 to \\\u003C16 years: maximum serum creatinine (mg\u002FdL) 1.5 (male); 1.4 (female), Age: ≥ 16 years: maximum serum creatinine (mg\u002FdL) 1.7 (male); 1.4 (female)\n* Adequate cardiac function defined as:\n\n  * LVEF \\> 50% by ECHO\n  * QTc interval ≤ 450 msec for male participants, ≤ 470 msec for female participants after electrolytes have been corrected.\n* Hypertension:\n\n  * Patients 2-12.99 years of age must have a blood pressure that is ≤ 95th percentile +10 mmHg for age, height, and gender at the time of enrollment (with or without the use of anti-hypertensive medications).\n  * Patients ≥ 13 years of age must have a blood pressure ≤ 140\u002F90 mmHg at the time of enrollment (with or without the use of anti-hypertensive medications).\n\n    * Note for patients of all ages: Adequate blood pressure can be achieved using medication for the treatment of hypertension.\n* Participants of childbearing\u002Fchild-fathering potential must agree to use contraception.\n* Participants and\u002For guardian have the ability to understand and the willingness to sign a written informed consent document according to institutional guidelines.\n* Participants who are receiving P-gp and BCRP inhibitors must have received their last dose a week or 5 half-lives (whichever is greater) prior to the first mirdametinib dose.\n\nInclusion Criteria: Phase 1: Progressive or Recurrent Low-Grade Glioma without Previous MEKi exposure\n\n* Participant's tumor must have unambiguously progressed, relapsed, or recurred during or after the most recent prior therapy (chemotherapy or radiotherapy) and pseudoprogression or treatment-related tumor changes have, in the opinion of the investigator, been thoroughly vetted.\n\n  * Progression may be radiographic or clinical (i.e. vision deterioration thought to be related to tumor in patients with optic pathway tumors, or neurologic deterioration thought to be related to tumor) but it must be unequivocal and sufficient to warrant treatment in the opinion of the investigator.\n* Prior therapy:\n\n  * Patients who have received the following:\n\n    * ≤ 3 prior treatment regimens with either myelosuppressive chemotherapy or biologic agents and\u002For\n    * focal radiotherapy\n* Note that a treatment regimen is defined as a single agent (chemotherapeutic or biologic), or a sequential combination of therapies that can include radiotherapy (with or without concurrent radiosensitizer, chemotherapy, or biologic therapy) followed by maintenance therapy (either single or combination) given over a period of time at either diagnosis or relapse.\n* Chemotherapy:\n\n  * Participant must have received their last dose of myelosuppressive anticancer chemotherapy at least 21 days prior to study enrollment or at least 42 days if nitrosourea.\n* Monoclonal antibody treatment and agents with known prolonged half-lives:\n\n  * Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the agent ≥ 28 days prior to study enrollment\n* MEK inhibitors:\n\n  * Patients must not have received prior exposure to any MEK inhibitors\n* XRT\u002FExternal Beam Irradiation including Protons:\n\n  * Participant must have had their last fraction of radiation ≥ 3 months prior to study enrollment\n\nInclusion Criteria: Phase 2, Cohort 1: Newly Diagnosed and\u002For previously untreated (except surgery) Low-Grade Glioma\n\n* No prior anti-cancer treatment except surgery.\n* In the opinion of the investigator tumor must warrant treatment defined as any of the following: unsafe to observe, unequivocally progressing on serial imaging, tumor is causing or at high risk of causing neurologic or vision-related deficits.\n\nInclusion Criteria: Phase 2, Cohort 2: Progressive or Recurrent Low-Grade Glioma without Previous MEK Inhibitor Exposure\n\n* Participant's tumor must have unambiguously progressed, relapsed, or recurred during or after the most recent prior therapy (chemotherapy or radiotherapy) and pseudoprogression or treatment-related tumor changes have, in the opinion of the investigator, been thoroughly vetted.\n\n  * Progression may be radiographic or clinical (i.e. vision deterioration thought to be related to tumor in patients with optic pathway tumors, or neurologic deterioration thought to be related to tumor) but it must be unequivocal and sufficient to warrant treatment in the opinion of the investigator.\n* Prior therapy:\n\n  * Chemotherapy:\n\n    * Participant must have received their last dose of myelosuppressive anticancer chemotherapy at least 21 days prior to study enrollment or at least 42 days if nitrosourea.\n  * Monoclonal antibody treatment and agents with known prolonged half-lives:\n\n    * Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the agent ≥ 28 days prior to study enrollment\n  * MEK inhibitors:\n\n    * Patients must not have received prior exposure to any MEK inhibitors\n  * XRT\u002FExternal Beam Irradiation including Protons:\n\n    * Participant must have had their last fraction of radiation ≥ 3 months prior to study enrollment.\n* Note that for this cohort, there are no limitations on number of prior treatment regimens and participants who have received craniospinal radiation are eligible\n\nInclusion Criteria: Phase 2, Cohort 3: Progressive or Recurrent Low-Grade Glioma with Previous MEK inhibitor Exposure\n\n* Cohort 3A (MEKi responders): Patients who previously received 6 or more cycles of any MEK inhibitor (including mirdametinib) and did NOT progress while on active MEK inhibitor therapy.\n\n  * The progression must have occurred off MEK inhibitor therapy\n  * Participant's tumor must have unambiguously relapsed or clinically progressed. Progression may be radiographic or clinical (i.e. vision deterioration thought to be related to tumor in patients with optic pathway tumors, or neurologic deterioration thought to be related to tumor) but it must be unequivocal and sufficient to warrant treatment in the opinion of the investigator.\n  * Patient must not have discontinued MEKi (specifically mirdametinib) for unacceptable toxicity, and in the opinion of the PI be able to tolerate subsequent courses of MEKi therapy.\n  * Patients must have received treatment with a MEK inhibitor for ≥6 cycles and showed no signs of progression while on active MEK inhibitor therapy.\n  * Patients who received additional anti-tumor therapy following discontinuation of MEK inhibitor can be enrolled in this cohort.\n* Prior Therapy:\n\n  * Chemotherapy:\n\n    * Participant must have received their last dose of myelosuppressive anticancer chemotherapy at least 21 days prior to study enrollment or at least 42 days if nitrosourea.\n  * Monoclonal antibody treatment and agents with known prolonged half-lives:\n\n    * Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the agent ≥ 28 days prior to study enrollment.\n  * MEK inhibitors:\n\n    * Participant must have received their last dose of MEKi at least 3 weeks prior to study enrollment.\n  * XRT\u002FExternal Beam Irradiation including Protons:\n\n    * Participant must have had their last fraction of radiation ≥ 3 months prior to study enrollment.\n* Note that for this cohort, there are no limitations on number of prior treatment regimens and participants who have received craniospinal radiation are eligible\n* Cohort 3B (MEKi non-responders): Patients with previous exposure to alternative MEK inhibitors (excluding mirdametinib) who progressed while on active MEK inhibitor therapy\n\n  * Participant's tumor must have unambiguously relapsed or clinically progressed.\n  * Progression may be radiographic or clinical (i.e. vision deterioration thought to be related to tumor in patients with optic pathway tumors, or neurologic deterioration thought to be related to tumor) but it must be unequivocal and sufficient to warrant treatment in the opinion of the investigator. Progression or recurrence must have occurred while on active MEK inhibitor therapy (excluding mirdametinib)\n  * Participants are eligible regardless of how many prior cycles were received or prior history of response (i.e. PR, Major Response, or CR)\n* Patients who received additional anti-tumor therapy following discontinuation of MEK inhibitor can be enrolled in this cohort as long as they meet the above criteria.\n* Prior Therapy:\n\n  * Chemotherapy:\n\n    * Participant must have received their last dose of myelosuppressive anticancer chemotherapy at least 21 days prior to study enrollment or at least 42 days if nitrosourea.\n  * Monoclonal antibody treatment and agents with known prolonged half-lives:\n\n    * Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the agent ≥ 28 days prior to study enrollment.\n  * Alternative MEK inhibitor:\n\n    * Participant must have received their last dose of MEKi (excluding mirdametinib) at least 3 weeks prior to study enrollment.\n  * XRT\u002FExternal Beam Irradiation including Protons:\n\n    * Participant must have had their last fraction of radiation ≥ 3 months prior to study enrollment.\n* Note that for this cohort, there are no limitations on number of prior treatment regimens and participants who have received craniospinal radiation are eligible.\n\nExclusion Criteria: Phase 1 and Phase 2, All Cohorts\n\n* Participants whose tumor on central review is any of the following:\n\n  * High-grade (WHO III or IV)\n  * Subependymal giant cell astrocytoma\n  * Ependymoma\n  * Histone H3 K27M\u002FK28M or G34\u002FG35-mutant\n  * BRAF V600 mutant\n  * NTRK1\u002F2\u002F3, ALK, or ROS1 fusion-positive\n  * IDH 1\u002F2 mutant\n* Participant who is currently receiving any other anticancer or investigational agents (\\^11C-methionine allowed) or still recovering from acute toxicity potentially related to the agent.\n* Ophthalmologic Conditions\n\n  * Patients with central serous retinopathy\n  * Patients with retinal vein occlusion or retinal detachment\n  * Patients with uncontrolled glaucoma\n\n    * If checking pressure is clinically indicated and feasible per patient's age and ability to complete exam, patients with IOP \\> 22 mmHg or ULN adjusted by age are not eligible\n* Participants with other clinically significant medical disorders (i.e. serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that in the investigator's judgement could compromise their ability to tolerate or absorb protocol therapy or would interfere with the study procedures or results.\n* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for 16 weeks after stopping study therapy are not eligible.\n* Participants are excluded if unable to comply with protocol guidelines.","ALL","2 Years","24 Years",{"count":86,"type":87},132,"ESTIMATED","INTERVENTIONAL",[90,91],"PHASE1","PHASE2","This is an open-label, multi-center, Phase 1\u002F2 study of the brain-penetrant MEK inhibitor, mirdametinib (PD-0325901), in patients with pediatric low-grade glioma (pLGG).",[94,95,96],"Low-Grade Glioma","Recurrent Low-Grade Glioma","Progressive Low-Grade Glioma",[98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127],"Brain tumors in Adolescent","Brain tumors in Children","Brain tumors in Young Adults","Astrocytic tumor","Glioneuronal tumor","Neuroepithelial tumor, not otherwise specified (NOS)","Neuroepithelial tumor, not elsewhere classified (NEC)","Pilocytic astrocytoma","Pilomyxoid astrocytoma","Pleomorphic xanthroastrocytoma","Ganglioglioma","Gangliocytoma","Diffuse glioma","Diffuse astrocytoma","Oligodendroglioma","Oligoastrocytoma","Papillary glioneuronal tumor","Rosette-forming glioneuronal tumor","Diffuse leptomeningeal glioneuronal tumor","Central neurocytoma","Extraventricular neurocytoma","Angiocentric glioma","Dysembryoplastic neuroepithelial tumor (DNET)","Septal Dysembryoplastic neuroepithelial tumor (DNET)","Myxoid glioneuronal tumor","Tectal glioma","Desmoplastic infantile astrocytoma","Desmoplastic infantile ganglioglioma","Polymorphous low-grade neuroepithelial tumor of the young","Multinodular and vacuolating neuronal tumor","2026-02-02",{"date":130,"type":131},"2026-02-04","ACTUAL",{"date":133,"type":131},"2021-06-21",{"date":135,"type":87},"2031-06",{"name":5,"class":6},1]