RECRUITING Phase 3 ClinicalTrials.gov

A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma

Sponsor: National Cancer Institute (NCI) • ClinicalTrials.gov ID: NCT04166409

Registry updated: 2026-09-11

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Description

This phase III trial compares the effect of selumetinib versus the standard of care treatment with carboplatin and vincristine (CV) in treating patients with newly diagnosed or previously untreated low-grade glioma (LGG) that does not have a genetic abnormality called BRAFV600E mutation and is not associated with systemic neurofibromatosis type 1. Selumetinib works by blocking some of the enzymes needed for cell growth and may kill tumor cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Vincristine is in a class of medications called vinca alkaloids. It works by stopping tumor cells from growing and dividing and may kill them. The overall goal of this study is to see if selumetinib works just as well as the standard treatment of CV for patients with LGG. Another goal of this study is to compare the effects of selumetinib versus CV in subjects with LGG to find out which is better. Additionally, this trial will also examine if treatment with selumetinib improves the quality of life for subjects who take it.

Interventions

Biospecimen Collection (Procedure)
Undergo blood sample collection
Carboplatin (Drug)
Given IV
Echocardiography Test (Procedure)
Undergo ECHO
Magnetic Resonance Imaging (Procedure)
Undergo MRI
Questionnaire Administration (Other)
Ancillary studies
Selumetinib Sulfate (Drug)
Given PO
Vincristine Sulfate (Drug)
Given IV

Eligibility criteria

Inclusion Criteria: * Patients must be \>= 2 years and =\< 21 years at the time of enrollment * Patients must have a body surface area (BSA) of \>= 0.5 m\^2 at enrollment * Patients must have non-neurofibromatosis type 1 (non-NF1) low-grade glioma (LGG) without a BRAFV600E mutation as confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1 (NCT02402244) Childhood Cancer Data Initiative (CCDI)-MCI, or accepted Clinical Laboratory Improvement Act (CLIA)-certified test and that has not been treated with any modality besides surgery. Note: Patients may be newly-diagnosed OR previously diagnosed, and there is no required time frame between biopsy/surgery and treatment initiation. * Patients with residual tumor after resection or progressive tumor after initial diagnosis (with or without surgery) who have not received treatment (chemotherapy and/or radiation) are eligible * Patients must have two-dimensional measurable tumor \>= 1 cm\^2 to be eligible * Patients with ependymoma are not eligible * Eligible histologies will include all tumors considered low-grade glioma or low-grade astrocytoma (World Health Organization \[WHO\] grade I and II) by 5th edition WHO classification of central nervous system (CNS) tumors with the exception of subependymal giant cell astrocytoma * Patients with metastatic disease or multiple independent primary LGG are eligible * Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 OR a serum creatinine based on age/sex as follows (performed within 7 days prior to enrollment): * Age: Maximum Serum Creatinine (mg/dL) * 2 to \< 6 years: 0.8 mg/dL (male); 0.8 mg/dL (female) * 6 to \< 10 years: 1 mg/dL (male); 1 mg/dL (female) * 10 to \< 13 years: 1.2 mg/dL (male); 1.2 mg/dL (female) * 13 to \< 16 years: 1.5 mg/dL (male); 1.4 mg/dL (female) * \>= 16 years: 1.7 mg/dL (male); 1.4 mg/dL (female) * Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment) (children with a diagnosis of Gilbert's syndrome will be allowed on study regardless of their total and indirect \[unconjugated\] bilirubin levels as long as their direct \[conjugated\] bilirubin is \< 3.1 mg/dL) * Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (performed within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L * Albumin \>= 2 g/dL (performed within 7 days prior to enrollment) * Left ventricular ejection fraction (LVEF) \>= 53% (or institutional normal; if the LVEF result is given as a range of values, then the upper value of the range will be used) by echocardiogram (performed within 4 weeks prior to enrollment) * Corrected QT (QTc) interval =\< 450 msec by electrocardiography (EKG) (performed within 4 weeks prior to enrollment) * Absolute neutrophil count \>= 1,000/uL (unsupported) (performed within 7 days prior to enrollment) * Platelets \>= 100,000/uL (unsupported) (performed within 7 days prior to enrollment) * Hemoglobin \>= 8 g/dL (may be supported) (performed within 7 days prior to enrollment) * Patients with a known seizure disorder must be stable and must not have experienced a significant increase in seizure frequency within 2 weeks prior to enrollment * Patients 2-17 years of age must have a blood pressure that is =\< 95th percentile for age, height, and sex at the time of enrollment (with or without the use of anti-hypertensive medications) * Patients \>= 18 years of age must have a blood pressure =\< 130/80 mmHg at the time of enrollment (with or without the use of anti-hypertensive medications) * Note for patients of all ages: Adequate blood pressure can be achieved using medication for the treatment of hypertension * All patients must have ophthalmology toxicity assessments performed within 8 weeks prior to enrollment * For all patients, an MRI of the brain (with orbital cuts for optic pathway tumors) and/or spine (depending on the site(s) of primary disease) with and without contrast must be performed within 8 weeks prior to enrollment * Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age * Patients must have the ability to swallow whole capsules * All patients and/or their parents or legal guardians must sign a written informed consent * All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met * All patients have signed an appropriate consent form and Health Insurance Portability and Accountability Act (HIPAA) authorization form (if applicable) * All patients have been consented and enrolled on APEC14B1 (NCT02402244) Part A for Pre-Enrollment Eligibility Screening for ACNS1833 Exclusion Criteria: * Patients must not have received any prior tumor-directed therapy including chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant. Prior surgical intervention (with the exclusion of laser interstitial thermal therapy \[LITT\]) is permitted * Patients with a concurrent malignancy or history of treatment (other than surgery) for another tumor within the last year are ineligible * Patients with diffuse intrinsic pontine tumors as seen on MRI (\> 2/3 of pons involvement on imaging) are not eligible even if biopsy reveals grade I/II histology * Patients may not be receiving any other investigational agents * Patients with any serious medical or psychiatric illness/condition, including substance use disorders or ophthalmological conditions, likely in the judgment of the investigator to interfere or limit compliance with study requirements/treatment * Patients who, in the opinion of the investigator, are not able to comply with the study procedures are not eligible * Female patients who are pregnant are not eligible 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 * Lactating females who plan to breastfeed their infants are not eligible * 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 1 week after stopping study therapy are not eligible. * Note: Women study participants of child-bearing potential must use acceptable contraception during the study and for 1 week (7 days) after the last dose of selumetinib. Men study participants with sexual partners who are pregnant or who are of child-bearing potential must use acceptable contraception during the study and for 1 week (7 days) after the last dose of study agent. Acceptable contraception includes implants, injectables, or oral contraceptives (all combined with barrier methods), some intrauterine devices (IUDs), vasectomy or abstinence * Known genetic disorder that increases risk for coronary artery disease. Note: The presence of dyslipidemia in a family with a history of myocardial infarction is not in itself an exclusion unless there is a known genetic disorder documented * Symptomatic heart failure * New York Health Association (NYHA) class II-IV prior or current cardiomyopathy * Severe valvular heart disease * History of atrial fibrillation * Current or past history of central serous retinopathy * Current or past history of retinal vein occlusion or retinal detachment * Patients with uncontrolled glaucoma * If checking pressure is clinically indicated, patients with intraocular pressure (IOP) \> 22 mmHg or ULN adjusted by age are not eligible * Supplementation with vitamin E greater than 100% of the daily recommended dose. Any multivitamin containing vitamin E must be stopped prior to study enrollment even if less than 100% of the daily recommended dosing for vitamin E * Surgery within 2 weeks prior to enrollment, with the exception of surgical biopsy, placement of a vascular access device or cerebral spinal fluid (CSF) diverting procedure such as endoscopic third ventriculostomy (ETV) and ventriculoperitoneal (VP) shunt. * Note: Patients must have healed from any prior surgery * Patients who have an uncontrolled infection are not eligible

Conditions

Low Grade Astrocytoma Low Grade Glioma Metastatic Low Grade Astrocytoma Metastatic Low Grade Glioma WHO Grade 1 Glioma WHO Grade 2 Glioma

Locations

Children's Hospital of Alabama — Birmingham, Alabama, United States
Banner Children's at Desert — Mesa, Arizona, United States
Phoenix Childrens Hospital — Phoenix, Arizona, United States
Arkansas Children's Hospital — Little Rock, Arkansas, United States
Loma Linda University Medical Center — Loma Linda, California, United States
Miller Children's and Women's Hospital Long Beach — Long Beach, California, United States
Children's Hospital Los Angeles — Los Angeles, California, United States
Cedars-Sinai Medical Center — Los Angeles, California, United States
Mattel Children's Hospital UCLA — Los Angeles, California, United States
Kaiser Permanente-Oakland — Oakland, California, United States
Children's Hospital of Orange County — Orange, California, United States
Lucile Packard Children's Hospital Stanford University — Palo Alto, California, United States
Rady Children's Hospital - San Diego — San Diego, California, United States
UCSF Medical Center-Mission Bay — San Francisco, California, United States
Children's Hospital Colorado — Aurora, Colorado, United States
Connecticut Children's Medical Center — Hartford, Connecticut, United States
Yale University — New Haven, Connecticut, United States
Alfred I duPont Hospital for Children — Wilmington, Delaware, United States
Children's National Medical Center — Washington D.C., District of Columbia, United States
Golisano Children's Hospital of Southwest Florida — Fort Myers, Florida, United States
UF Health Cancer Institute - Gainesville — Gainesville, Florida, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital — Hollywood, Florida, United States
Nemours Children's Clinic-Jacksonville — Jacksonville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center — Miami, Florida, United States
Nicklaus Children's Hospital — Miami, Florida, United States
AdventHealth Orlando — Orlando, Florida, United States
Arnold Palmer Hospital for Children — Orlando, Florida, United States
Nemours Children's Hospital — Orlando, Florida, United States
Nemours Children's Clinic - Pensacola — Pensacola, Florida, United States
Sacred Heart Hospital — Pensacola, Florida, United States
Johns Hopkins All Children's Hospital — St. Petersburg, Florida, United States
Saint Joseph's Hospital/Children's Hospital-Tampa — Tampa, Florida, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital — Atlanta, Georgia, United States
Kapiolani Medical Center for Women and Children — Honolulu, Hawaii, United States
Saint Luke's Cancer Institute - Boise — Boise, Idaho, United States
Lurie Children's Hospital-Chicago — Chicago, Illinois, United States
University of Illinois — Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States
OSF Children's Hospital of Illinois — Peoria, Illinois, United States
Southern Illinois University School of Medicine — Springfield, Illinois, United States
Riley Hospital for Children — Indianapolis, Indiana, United States
Ascension Saint Vincent Indianapolis Hospital — Indianapolis, Indiana, United States
Blank Children's Hospital — Des Moines, Iowa, United States
University of Iowa/Holden Comprehensive Cancer Center — Iowa City, Iowa, United States
University of Kentucky/Markey Cancer Center — Lexington, Kentucky, United States
Norton Children's Hospital — Louisville, Kentucky, United States
Children's Hospital New Orleans — New Orleans, Louisiana, United States
Eastern Maine Medical Center — Bangor, Maine, United States
Maine Children's Cancer Program — Scarborough, Maine, United States
Johns Hopkins University/Sidney Kimmel Cancer Center — Baltimore, Maryland, United States
Walter Reed National Military Medical Center — Bethesda, Maryland, United States
Massachusetts General Hospital Cancer Center — Boston, Massachusetts, United States
Dana-Farber Cancer Institute — Boston, Massachusetts, United States
C S Mott Children's Hospital — Ann Arbor, Michigan, United States
Children's Hospital of Michigan — Detroit, Michigan, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital — Grand Rapids, Michigan, United States
Corewell Health Children's — Royal Oak, Michigan, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis — Minneapolis, Minnesota, United States
University of Minnesota/Masonic Cancer Center — Minneapolis, Minnesota, United States
Mayo Clinic in Rochester — Rochester, Minnesota, United States
University of Mississippi Medical Center — Jackson, Mississippi, United States
Children's Mercy Hospitals and Clinics — Kansas City, Missouri, United States
Cardinal Glennon Children's Medical Center — St Louis, Missouri, United States
Washington University School of Medicine — St Louis, Missouri, United States
Children's Hospital and Medical Center of Omaha — Omaha, Nebraska, United States
University of Nebraska Medical Center — Omaha, Nebraska, United States
Morristown Medical Center — Morristown, New Jersey, United States
Albany Medical Center — Albany, New York, United States
Roswell Park Cancer Institute — Buffalo, New York, United States
NYU Langone Hospital - Long Island — Mineola, New York, United States
The Steven and Alexandra Cohen Children's Medical Center of New York — New Hyde Park, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone — New York, New York, United States
Memorial Sloan Kettering Cancer Center — New York, New York, United States
University of Rochester — Rochester, New York, United States
State University of New York Upstate Medical University — Syracuse, New York, United States
New York Medical College — Valhalla, New York, United States
UNC Lineberger Comprehensive Cancer Center — Chapel Hill, North Carolina, United States
Carolinas Medical Center/Levine Cancer Institute — Charlotte, North Carolina, United States
Duke University Medical Center — Durham, North Carolina, United States
East Carolina University — Greenville, North Carolina, United States
Wake Forest University Health Sciences — Winston-Salem, North Carolina, United States
Sanford Broadway Medical Center — Fargo, North Dakota, United States
Children's Hospital Medical Center of Akron — Akron, Ohio, United States
Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States
Rainbow Babies and Childrens Hospital — Cleveland, Ohio, United States
Nationwide Children's Hospital — Columbus, Ohio, United States
Dayton Children's Hospital — Dayton, Ohio, United States
University of Oklahoma Health Sciences Center — Oklahoma City, Oklahoma, United States
Oregon Health and Science University — Portland, Oregon, United States
Geisinger Medical Center — Danville, Pennsylvania, United States
Penn State Children's Hospital — Hershey, Pennsylvania, United States
Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States
Saint Christopher's Hospital for Children — Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC — Pittsburgh, Pennsylvania, United States
Rhode Island Hospital — Providence, Rhode Island, United States
Medical University of South Carolina — Charleston, South Carolina, United States
Prisma Health Richland Hospital — Columbia, South Carolina, United States
BI-LO Charities Children's Cancer Center — Greenville, South Carolina, United States
East Tennessee Childrens Hospital — Knoxville, Tennessee, United States
Saint Jude Children's Research Hospital — Memphis, Tennessee, United States
Vanderbilt University/Ingram Cancer Center — Nashville, Tennessee, United States
Dell Children's Medical Center of Central Texas — Austin, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas — Dallas, Texas, United States
El Paso Children's Hospital — El Paso, Texas, United States
Cook Children's Medical Center — Fort Worth, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center — Houston, Texas, United States
UT MD Anderson Cancer Center — Houston, Texas, United States
Covenant Children's Hospital — Lubbock, Texas, United States
UMC Cancer Center / UMC Health System — Lubbock, Texas, United States
Children's Hospital of San Antonio — San Antonio, Texas, United States
Methodist Children's Hospital of South Texas — San Antonio, Texas, United States
University of Texas Health Science Center at San Antonio — San Antonio, Texas, United States
Primary Children's Hospital — Salt Lake City, Utah, United States
University of Vermont and State Agricultural College — Burlington, Vermont, United States
Children's Hospital of The King's Daughters — Norfolk, Virginia, United States
VCU Massey Comprehensive Cancer Center — Richmond, Virginia, United States
Carilion Children's — Roanoke, Virginia, United States
Seattle Children's Hospital — Seattle, Washington, United States
Providence Sacred Heart Medical Center and Children's Hospital — Spokane, Washington, United States
Mary Bridge Children's Hospital and Health Center — Tacoma, Washington, United States
Madigan Army Medical Center — Tacoma, Washington, United States
West Virginia University Healthcare — Morgantown, West Virginia, United States
University of Wisconsin Carbone Cancer Center - University Hospital — Madison, Wisconsin, United States
Children's Hospital of Wisconsin — Milwaukee, Wisconsin, United States
British Columbia Children's Hospital — Vancouver, British Columbia, Canada
Janeway Child Health Centre — St. John's, Newfoundland and Labrador, Canada
IWK Health Centre — Halifax, Nova Scotia, Canada
The Montreal Children's Hospital of the MUHC — Montreal, Quebec, Canada
Centre Hospitalier Universitaire Sainte-Justine — Montreal, Quebec, Canada
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont — Sherbrooke, Quebec, Canada
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL) — Québec, Canada
HIMA San Pablo Oncologic Hospital — Caguas, Puerto Rico

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Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

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