[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100658268":3},{"organization":4,"outcomesModule":7,"designInfo":50,"detailedDescription":57,"studyPopulation":53,"armGroups":58,"interventions":72,"overallOfficials":217,"centralContacts":53,"locations":53,"responsibleParty":221,"collaborators":53,"id":223,"slug":224,"hasResults":225,"nctId":226,"briefTitle":227,"officialTitle":228,"acronym":53,"eligibilityCriteria":229,"healthyVolunteers":225,"sex":230,"minAge":231,"maxAge":232,"enrollmentInfo":233,"targetDuration":53,"studyType":236,"phases":237,"briefSummary":240,"conditions":241,"keywords":53,"overallStatus":243,"whyStopped":53,"lastUpdateSubmitDate":244,"lastUpdatePostDateStruct":245,"startDateStruct":248,"completionDateStruct":250,"leadSponsor":252,"locationsCount":53},{"fullName":5,"class":6},"Children's Oncology Group","NETWORK",{"primaryOutcomes":8,"secondaryOutcomes":21,"otherOutcomes":30},[9,13,17],{"measure":10,"description":11,"timeFrame":12},"Occurrence of dose limiting toxicity chemoradiotherapy (DLT) (phase 1)","Will report the sample proportion of analysis patients experiencing DLTs with binominal exact 95% confidence intervals by dose level. Other toxicity data will also be described as appropriate for supportive analyses.","From the start of chemoradiotherapy until 4 weeks after completing chemoradiotherapy",{"measure":14,"description":15,"timeFrame":16},"Occurrence of DLT for maintenance therapy (phase 1)","Will report the sample proportion of analysis patients experiencing DLTs with binominal exact 95% confidence intervals by dose level. Other toxicity data will also be described as appropriate for supportive analyses. A planned supportive analysis will descriptively assess any interaction between increasing chemoradiotherapy dose and maintenance therapy tolerability.","From the start of the first maintenance therapy cycle until the end of the first maintenance therapy cycle (Cycle = 42 days)",{"measure":18,"description":19,"timeFrame":20},"Event free survival (EFS)","Will test whether the EFS in the prospective patients is superior to the historical control using a stratified log-rank test adjusting for resection status (subtotal resection \\[STR\\] or gross total resection\u002Fnear total resection GTR\u002FNTR\\]) with a one-sided type-1 error rate of 0.10. The primary analysis will also report the Kaplan-Meier estimates of the prospective and historical control patients. Planned supportive analyses will assess whether EFS differs by resection status within the prospective patients, and conduct separate resection status-specific comparisons between the prospective and corresponding historical control patients. These analyses will use unadjusted log-rank tests.","From enrollment to the first of any of the following events: disease progression, disease recurrence, second malignant neoplasm, or death from any cause, up to 5 years",[22,26],{"measure":23,"description":24,"timeFrame":25},"Overall response","STR patients will be analyzed separately from GTR\u002FNTR patients, as GTR\u002FNTR patients are only evaluable for experiencing progressive disease. Analyses will also be reported separately by dose level. We will report the response rates using the respective sample proportions and exact binomial two-sided 95% confidence intervals.","After completing chemoradiotherapy (up to 49 days) and after completing maintenance therapy (Up to 6 cycles (Cycle= 42 days))",{"measure":27,"description":28,"timeFrame":29},"Overall survival","Will be summarized by the Kaplan Meyer method with similar considerations for the analysis population and intercurrent events as for EFS.","From enrollment to death from any cause, up to 5 years",[31,35,38,41,44,47],{"measure":32,"description":33,"timeFrame":34},"Correlate presence of tumor cell free deoxyribonucleic acid (DNA) with methylation profiling and clinical outcome","Will explore the associations between tumor cell free DNA and EFS using Cox models. Initial analyses will use univariable models, and suitable multivariable models will be considered, subject to data constraints (e.g., number of events).Cox models incorporating these covariates as baseline covariates will be used for covariates available at the time of enrollment, and landmark analyses or time-varying covariates will be used for analyses with post-enrollment covariates.","Up to 5 years",{"measure":36,"description":37,"timeFrame":34},"Correlate histopathologic grade with clinical outcome","Will explore the associations between histopathologic grade and EFS using Cox models. Initial analyses will use univariable models, and suitable multivariable models will be considered, subject to data constraints (e.g., number of events).Cox models incorporating these covariates as baseline covariates will be used for covariates available at the time of enrollment, and landmark analyses or time-varying covariates will be used for analyses with post-enrollment covariates.",{"measure":39,"description":40,"timeFrame":34},"Correlate gene expression profiles with clinical outcome","Will explore the associations between gene expression profiles and EFS using Cox models. Initial analyses will use univariable models, and suitable multivariable models will be considered, subject to data constraints (e.g., number of events).Cox models incorporating these covariates as baseline covariates will be used for covariates available at the time of enrollment, and landmark analyses or time-varying covariates will be used for analyses with post-enrollment covariates.",{"measure":42,"description":43,"timeFrame":34},"Correlate epigenetic profiles with clinical outcome","Will explore the associations between epigenetic profiles and EFS using Cox models. Initial analyses will use univariable models, and suitable multivariable models will be considered, subject to data constraints (e.g., number of events).Cox models incorporating these covariates as baseline covariates will be used for covariates available at the time of enrollment, and landmark analyses or time-varying covariates will be used for analyses with post-enrollment covariates.",{"measure":45,"description":46,"timeFrame":34},"Correlate chromosome copy number status with clinical outcome","Will explore the associations between chromosome copy number status and EFS using Cox models. Initial analyses will use univariable models, and suitable multivariable models will be considered, subject to data constraints (e.g., number of events).Cox models incorporating these covariates as baseline covariates will be used for covariates available at the time of enrollment, and landmark analyses or time-varying covariates will be used for analyses with post-enrollment covariates.",{"measure":48,"description":49,"timeFrame":34},"Bank tumor, blood and cerebrospinal fluid specimens for future studies and assessment of immune and molecular signatures","The number of patients consenting to collect tumor, blood and cerebrospinal fluid specimens, along with the number of submitted specimens, will be recorded as a part of routine study monitoring.",{"allocation":51,"interventionModel":52,"interventionModelDescription":53,"primaryPurpose":54,"observationalModel":53,"timePerspective":53,"maskingInfo":55},"NA","SINGLE_GROUP",null,"TREATMENT",{"masking":56,"maskingDescription":53,"whoMasked":53},"NONE","PRIMARY OBJECTIVE:\n\nI. To assess the safety of intravenous (IV) bolus fluorouracil (5-FU) in combination with standard-of-care radiation therapy and to determine the recommended phase 2 dose (RP2D) when administered concurrently with radiation therapy (RT) in children with newly-diagnosed localized high-risk posterior fossa type A (PFA) ependymoma. (Phase 1) II. To determine the safety of and RP2D for oral tretinoin (all trans retinoic acid \\[ATRA\\]) on an intermittent schedule in combination with bolus IV fluorouracil (5-FU) in children with newly-diagnosed localized high-risk PFA ependymoma as maintenance therapy after fluorouracil-based chemoradiotherapy. (Phase 1) III. To compare event-free survival (EFS) in children with newly-diagnosed high-risk PFA ependymoma treated with resection, radiation therapy (RT), fluorouracil (5-FU), and ATRA at the RP2D with historical controls from ACNS0831. (Phase 2)\n\nSECONDARY OBJECTIVES:\n\nI. To preliminarily define the antitumor activity of IV bolus fluorouracil (5-FU) in combination with standard-of-care radiation therapy and of oral tretinoin (ATRA) on an intermittent schedule in combination with bolus IV fluorouracil (5-FU) maintenance for pediatric patients with newly diagnosed localized high-risk PFA ependymoma within the confines of a Phase 1 study. (Phase 1) II. To estimate overall survival (OS) in children with newly-diagnosed high-risk PFA ependymoma treated with resection, RT, fluorouracil (5-FU), and oral tretinoin (ATRA) at the RP2D. (Phase 2)\n\nEXPLORATORY OBJECTIVES:\n\nI. To correlate presence of tumor cell free deoxyribonucleic acid (DNA) with methylation profiling and clinical outcome. (Phase 1\u002F2) II. To correlate histopathologic grade, gene expression profiles, epigenetic profiles and chromosome copy number status with clinical outcome. (Phase 1\u002F2) III. To bank tumor, blood and cerebrospinal fluid specimens for future studies and assessment of immune and molecular signatures that may predict response or resistance in high-risk PFA ependymoma. (Phase 1\u002F2)\n\nOUTLINE: This is a phase I, dose-escalation study of fluorouracil and tretinoin followed by a dose-expansion and phase II study.\n\nCHEMORADIOTHERAPY: Patients receive standard of care radiation therapy over 6 or 7 weeks. Starting on day 1, 2 or 3 of radiation, patients receive fluorouracil IV over 3-15 minutes on days 1 and 15, days 1, 8 and 15, or days 1, 8, 15 and 22 depending upon assigned dose level. Treatment is given in the absence of disease progression or unacceptable toxicity.\n\nMAINTENANCE CHEMOTHERAPY: Four weeks after completion of chemoradiotherapy, patients receive fluorouracil IV on days 1, 8, 15 and 22 of each cycle and tretinoin orally (PO) three times daily (TID) on days 1-3, 8-10, 15-17 and 22-24 of each cycle. Cycles repeat every 42 days for 6 cycles in the absence of disease progression or unacceptable toxicity.\n\nPatients undergo echocardiography or multigated acquisition (MUGA) scan, magnetic resonance imaging (MRI), lumbar puncture, and optional blood sample collection throughout the study.\n\nAfter completion of study treatment, patients are followed up at relapse, every 4 months for years 1-3, then every 6 months for years 3-5.",[59],{"label":60,"type":61,"description":62,"interventionNames":63},"Treatment (radiation, fluorouracil, tretinoin)","EXPERIMENTAL","CHEMORADIOTHERAPY: Patients receive standard of care radiation therapy over 6 or 7 weeks. Starting on day 1, 2 or 3 of radiation, patients receive fluorouracil IV over 3-15 minutes on days 1 and 15, days 1, 8 and 15, or days 1, 8, 15 and 22 depending upon assigned dose level. Treatment is given in the absence of disease progression or unacceptable toxicity.\n\nMAINTENANCE CHEMOTHERAPY: Four weeks after completion of chemoradiotherapy, patients receive fluorouracil IV on days 1, 8, 15 and 22 of each cycle and tretinoin PO TID on days 1-3, 8-10, 15-17 and 22-24 of each cycle. Cycles repeat every 42 days for 6 cycles in the absence of disease progression or unacceptable toxicity.\n\nPatients undergo echocardiography or MUGA, MRI, lumbar puncture, and optional blood sample collection throughout the study.",[64,65,66,67,68,69,70,71],"Procedure: Biospecimen Collection","Procedure: Echocardiography Test","Drug: Fluorouracil","Procedure: Lumbar Puncture","Procedure: Magnetic Resonance Imaging","Procedure: Multigated Acquisition Scan","Radiation: Radiation Therapy","Drug: Tretinoin",[73,83,90,116,123,143,161,179],{"type":74,"name":75,"description":76,"armGroupLabels":77,"otherNames":78},"PROCEDURE","Biospecimen Collection","Undergo blood and CSF sample collection",[60],[79,80,81,82],"Biological Sample Collection","Biospecimen Collected","Sample Collection","Specimen Collection",{"type":74,"name":84,"description":85,"armGroupLabels":86,"otherNames":87},"Echocardiography Test","Undergo echocardiography",[60],[88,89],"EC","Echocardiography",{"type":91,"name":92,"description":93,"armGroupLabels":94,"otherNames":95},"DRUG","Fluorouracil","Given IV",[60],[96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115],"5 Fluorouracil","5 Fluorouracilum","5 FU","5-Fluoro-2,4(1H, 3H)-pyrimidinedione","5-Fluorouracil","5-Fluracil","5-Fu","5FU","AccuSite","Carac","Fluoro Uracil","Fluouracil","Flurablastin","Fluracedyl","Fluracil","Fluril","Fluroblastin","Ribofluor","Ro 2-9757","Ro-2-9757",{"type":74,"name":117,"description":118,"armGroupLabels":119,"otherNames":120},"Lumbar Puncture","Undergo lumbar puncture",[60],[121,122],"LP","Spinal Tap",{"type":74,"name":124,"description":125,"armGroupLabels":126,"otherNames":127},"Magnetic Resonance Imaging","Undergo MRI",[60],[128,129,130,131,132,133,134,135,136,137,138,139,140,141,142],"Magnetic Resonance","Magnetic Resonance Imaging (MRI)","Magnetic resonance imaging (procedure)","Magnetic Resonance Imaging Scan","Medical Imaging, Magnetic Resonance \u002F Nuclear Magnetic Resonance","MR","MR Imaging","MRI","MRI Scan","MRIs","NMR Imaging","NMRI","Nuclear Magnetic Resonance Imaging","sMRI","Structural MRI",{"type":74,"name":144,"description":145,"armGroupLabels":146,"otherNames":147},"Multigated Acquisition Scan","Undergo MUGA scan",[60],[148,149,150,151,152,153,154,155,156,157,158,159,160],"Blood Pool Scan","Equilibrium Radionuclide Angiography","Gated Blood Pool Imaging","Gated Heart Pool Scan","MUGA","MUGA Scan","Multi-Gated Acquisition Scan","Radionuclide Ventriculogram Scan","Radionuclide Ventriculography","RNV Scan","RNVG","SYMA Scanning","Synchronized Multigated Acquisition Scanning",{"type":162,"name":163,"description":164,"armGroupLabels":165,"otherNames":166},"RADIATION","Radiation Therapy","Undergo standard of care radiation therapy",[60],[167,168,169,170,171,172,173,174,175,176,177,178],"Cancer Radiotherapy","Energy Type","ENERGY_TYPE","Irradiate","Irradiated","Irradiation","Radiation","Radiation Therapy, NOS","Radiotherapeutics","Radiotherapy","RT","Therapy, Radiation",{"type":91,"name":180,"description":181,"armGroupLabels":182,"otherNames":183},"Tretinoin","Given PO",[60],[184,185,186,187,188,189,190,191,192,193,194,195,196,197,198,199,200,201,202,203,204,205,206,207,208,209,210,211,212,213,214,215,216],"2,4,6,8-Nonatetraenoic acid, 3, 7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-, (all-E)-","Aberel","Airol","Aknoten","all trans-Retinoic acid","All-trans Retinoic Acid","All-trans Vitamin A Acid","all-trans-Retinoic acid","all-trans-Vitamin A acid","ATRA","Avita","beta-Retinoic Acid","Cordes Vas","Dermairol","Epi-Aberel","Eudyna","Renova","Retin-A","Retin-A MICRO","Retin-A-Micro","Retinoic Acid","Retisol-A","Ro 5488","Stieva-A","Stieva-A Forte","Trans Retinoic Acid","Trans Vitamin A Acid","trans-Retinoic Acid","Tretinoinum","Vesanoid","Vitamin A Acid","Vitamin A acid, all-trans-","Vitinoin",[218],{"name":219,"affiliation":5,"role":220},"Adam J Esbenshade","PRINCIPAL_INVESTIGATOR",{"type":222,"investigatorFullName":53,"investigatorTitle":53,"investigatorAffiliation":53,"oldNameTitle":53,"oldOrganization":53},"SPONSOR","100658268","phase-1-testing-safe-doses-of-anti-cancer-medicines-5-flurouracil-5-fu-and-tretinoin-atra-added-to-the-usual-cancer-treatment-of-ependymoma-100658268",false,"NCT07848568","Testing Safe Doses of Anti-Cancer Medicines, 5-Flurouracil (5-FU) and Tretinoin (ATRA), Added to the Usual Cancer Treatment of Ependymoma","A Phase 1\u002F2 Trial of Chemoradiotherapy With 5-Fluorouracil and Maintenance Chemotherapy for High-Risk Posterior Fossa Ependymoma","Inclusion Criteria:\n\n* PRE-ENROLLMENT: Patients must be \\> 12 months and \\\u003C 21 years of age at the time of enrollment\n* PRE-ENROLLMENT: Patient has newly diagnosed posterior fossa ependymoma based on institutional pathologic diagnosis\n* PRE-ENROLLMENT: The patient and\u002For their parents or legal guardians must have signed informed consent for APEC14B1 Part A - Eligibility Screening\n* PRE-ENROLLMENT: If relying on APEC14B1-MCI for molecular characterization, required specimens for molecular characterization should be submitted as soon as possible, preferably within 5 calendar days of definitive surgery\n* Patients must be \\> 12 months and \\\u003C 21 years at the time of study enrollment\n* Patients must be newly diagnosed, localized and have eligibility confirmed by central review of molecular reports\n* Histologically confirmed diagnosis of Posterior fossa ependymoma, group PFA\n* Molecular high risk features including Chromosome 1q gain and\u002For chromosome 6q loss\n* Patients must be enrolled on study within 56 days of definitive surgical resection. If applicable, the day of subsequent resection to remove residual tumor will be regarded as the day of definitive surgery and must be within a month (31 days) of the initial resection\n* Patients must have negative lumbar CSF cytology.\n\n  * Note: CSF cytology for staging should be performed no sooner than 14 days post operatively to avoid false positive CSF. Ideally, CSF should be obtained between Day 14 and Day 21 to allow for final staging status before enrollment onto the study. Patients with positive lumbar CSF cytology obtained 0 to 14 days after surgery should have lumbar cytology repeated to determine eligibility and final CSF status. Patients with negative CSF lumbar cytology from lumbar puncture obtained 0 to 14 days after surgery do not need cytology repeated. Patients with negative CSF cytology from lumbar puncture obtained prior to surgery do not need cytology repeated post-operatively.\n  * CSF cytology does not need to be repeated if within 87 days prior to enrollment regardless of timing\n* Patients must have localized disease. Pre and post-operative whole brain MRI with and without gadolinium and spine MRI with gadolinium must be performed\n\n  * Disease\u002Fstaging imaging studies, including MRI brain (post operative) and spine (pre or post-operative), must be obtained within 31 days prior to enrollment and start of protocol therapy (repeat if necessary)\n* No prior treatment other than surgical intervention and corticosteroids. Patients are allowed to have had more than one surgical resection prior to enrollment. For patients who have subsequent surgery, the day of the subsequent resection to remove residual tumor will be regarded as the day of definitive surgery and must be within a month (31 days) of initial resection\n* Known HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* Peripheral absolute neutrophil count (ANC) ≥ 1000\u002F µL (performed within 7 days prior to enrollment)\n* Platelet count ≥ 100,000\u002FµL (transfusion independent) (performed within 7 days prior to enrollment)\n* Hemoglobin ≥ 8 g\u002FdL (may receive red blood cell \\[RBC\\] transfusions) (transfusion independent) (performed within 7 days prior to enrollment)\n* Adequate Renal Function Defined As:\n\n  * A serum creatinine based on age\u002Fsex as follows (performed within 7 days prior to enrollment) OR\n\n    * 1 to \\\u003C 2 years: Maximum serum creatinine 0.6 mg\u002FdL (male), 0.6 mg\u002FdL (female)\n    * 2 to \\\u003C 6 years: Maximum serum creatinine 0.8 mg\u002FdL (male), 0.8 mg\u002FdL (female)\n    * 6 to \\\u003C 10 years: Maximum serum creatinine 1 mg\u002FdL (male), 1 mg\u002FdL (female)\n    * 10 to \\\u003C 13 years: Maximum serum creatinine 1.2 mg\u002FdL (male), 1.2 mg\u002FdL (female)\n    * 13 to \\\u003C 16 years: Maximum serum creatinine 1.5 mg\u002FdL (male), 1.4 mg\u002FdL (female)\n    * \\>= 16 years: Maximum serum creatinine 1.7 mg\u002FdL (male),1.4 mg\u002FdL (female)\n\n      * The threshold creatinine values in this Table were derived from the Schwartz formula for estimating glomerular filtration rate (GFR) utilizing child length and stature data published by the Center for Disease Control (CDC)\n  * a 24-hour urine Creatinine clearance ≥ 50 mL\u002Fmin\u002F1.73 m\\^2 (performed within 7 days prior to enrollment) OR\n  * a GFR ≥ 50 mL\u002Fmin\u002F1.73 m\\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard) (performed within 7 days prior to enrollment)\n\n    * Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable if using GFR for determine eligibility\n* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment)\n* Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \\[ALT\\]) ≤ 135 U\u002FL\\* (performed within 7 days prior to enrollment)\n\n  * Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U\u002FL\n* Central nervous system function defined as:\n\n  * Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled.\n  * Patients must not be in status epilepticus, a coma or assisted ventilation at the time of study enrollment\n* Adequate cardiac function\n\n  * Shortening fraction of ≥ 27% by echocardiogram, or\n  * Ejection fraction of ≥ 50% by echocardiogram, cardiac MRI, or radionuclide angiogram, AND\n  * For Patients ≥ 18 years:\n\n    * Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better\n* Test result showing no evidence of complete or partial absence of dihydropyrimidine dehydrogenase (DPYD) activity. This genetic test can be obtained at any time prior to enrollment at a College of American Pathology (CAP)\u002FClinical Laboratory Improvement Act (CLIA) certified laboratory. Patients with DPYD variants that result in complete or partial DPD deficiency are not permitted to enroll on this study\n\nExclusion Criteria:\n\n* Patients with metastatic disease by either MRI evaluation or lumbar CSF cytology are not eligible. Patients who are unable to undergo a lumbar puncture for assessment of CSF cytology are ineligible\n* Hypersensitivity to fluorouracil, tretinoin, other retinoids, or any component of the formulation\n* Personal history of Torsades de pointes, atrial fibrillation, supraventricular tachycardia (SVT), or heart failure; personal history of prolonged QT Syndrome; other uncontrolled arrhythmia in the past 6 months prior to study enrollment\n* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential\n* Lactating females who plan to breastfeed their infants\n* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation. Patients who could become pregnant should use effective contraception during treatment and 1 month following the last dose of tretinoin or for 3 months following last dose of fluorouracil, whichever is longer. Patients with partners who could become pregnant should also use effective contraception during treatment and for 1 week after the last dose of tretinoin or 3 months after the last dose of fluorouracil, whichever is longer","ALL","12 Months","21 Years",{"count":234,"type":235},70,"ESTIMATED","INTERVENTIONAL",[238,239],"PHASE1","PHASE2","This phase I\u002FII trial tests the safety, side effects best dose and how well giving fluorouracil and tretinoin along with standard of care radiation therapy works for the treatment of high risk posterior fossa ependymoma that has not spread to other parts of the body (localized). Fluorouracil is a type medication called an antimetabolite. It works by stopping cells from making DNA and it may kill tumor cells. Tretinoin, also called all-trans retinoic acid (ATRA), retinoic acid, and vitamin A acid is in a class of medications called retinoids. It is made in the body from vitamin A and helps cells to grow and develop, especially in the embryo. Laboratory made form of tretinoin works by slowing or stopping the growth of tumor cells. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. Giving fluorouracil and tretinoin along with standard of care radiation therapy may be safe, tolerable and\u002For effective in treating patients with localized high risk posterior fossa ependymoma.",[242],"Childhood Posterior Fossa Ependymoma","NOT_YET_RECRUITING","2026-09-23",{"date":246,"type":247},"2026-09-30","ACTUAL",{"date":249,"type":235},"2026-12-11",{"date":251,"type":235},"2037-06-30",{"name":5,"class":6}]