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RECRUITING

NCT04166409

PHASE3

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

Sponsor: National Cancer Institute (NCI)

View on ClinicalTrials.gov

Summary

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.

Official title: A Phase 3 Randomized Non-Inferiority Study of Carboplatin and Vincristine Versus Selumetinib (NSC# 748727) in Newly Diagnosed or Previously Untreated Low-Grade Glioma (LGG) Not Associated With BRAFV600E Mutations or Systemic Neurofibromatosis Type 1 (NF1)

Key Details

Gender

All

Age Range

2 Years - 21 Years

Study Type

INTERVENTIONAL

Enrollment

170

Start Date

2020-01-31

Completion Date

2030-12-31

Last Updated

2026-04-09

Healthy Volunteers

Conditions

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

Interventions

PROCEDURE

Biospecimen Collection

Undergo blood sample collection

DRUG

Carboplatin

Given IV

PROCEDURE

Echocardiography Test

Undergo ECHO

PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

OTHER

Questionnaire Administration

Ancillary studies

DRUG

Selumetinib Sulfate

Given PO

DRUG

Vincristine Sulfate

Given IV

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

Locations (132)

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

Saint Jude Midwest Affiliate

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

M D 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

Clinical Research Directory

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

Summary

Key Details

Conditions

Interventions

Eligibility Criteria

Locations (132)