A Study of the Drugs Selumetinib Versus Carboplatin/Vincristine in Patients With Neurofibromatosis and Low-Grade Glioma
A Phase 3 Randomized Study of Selumetinib Versus Carboplatin/Vincristine in Newly Diagnosed or Previously Untreated Neurofibromatosis Type 1 (NF1) Associated Low-Grade Glioma (LGG)
3 other identifiers
interventional
165
3 countries
132
Brief Summary
This phase III trial studies if selumetinib works just as well as the standard treatment with carboplatin/vincristine (CV) for subjects with NF1-associated low grade glioma (LGG), and to see if selumetinib is better than CV in improving vision in subjects with LGG of the optic pathway (vision nerves). Selumetinib is a drug that works by blocking some enzymes that low-grade glioma tumor cells need for their growth. This results in killing tumor cells. Chemotherapy drugs, such as carboplatin and vincristine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether selumetinib works better in treating patients with NF1-associated low-grade glioma compared to standard therapy with carboplatin and vincristine.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Jan 2020
Longer than P75 for phase_3
132 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 11, 2019
CompletedFirst Posted
Study publicly available on registry
March 12, 2019
CompletedStudy Start
First participant enrolled
January 15, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2027
April 13, 2026
February 1, 2026
8 years
March 11, 2019
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Event-free survival (EFS)
EFS is defined as time from randomization to the first occurrence of any of the following events: clinical or radiographic disease progression, disease recurrence, second malignant neoplasm, or death from any cause. Patients who are event-free will be censored at the time of last follow-up. Will estimate the hazard ratio based on a stratified Cox proportional hazards model and use Kaplan Meier (KM) methods to visualize and summarize the data.
From randomization to the first occurrence of any of the following events: clinical or radiographic disease progression, disease recurrence, second malignant neoplasm, or death from any cause, assessed up to 3 years after accrual completion
Number of participants with visual acuity (VA) improvement per arm
VA will be assessed using Teller acuity cards (TAC). A significant improvement in VA will be defined as a decrease of \>= 0.2 logMAR (corrected for age) from baseline (pre-treatment baseline) to end of about 12 months of treatment. The primary analysis will be based on per subject outcome (rather than per eye).
Baseline and end of about 12 months of treatment
Secondary Outcomes (8)
Radiographic tumor response rate
Assessed up to 3 years after accrual completion
Overall survival (OS)
From randomization until death from any cause or till the time of last follow-up for patients who are alive at the time of analysis, assessed up to 3 years after accrual completion
Change in VA using HOTV letter acuity testing
Baseline and end of about 12 months of treatment
Change in motor function
Baseline and approximately 12 months of treatment
Change in quality of life (QOL)
Baseline and 12 months of treatment
- +3 more secondary outcomes
Other Outcomes (17)
Change in circumpapillary retinal nerve fiber layer (cpRNFL) thickness by treatment arm
Baseline and 12 months
cpRNFL thickness at baseline by visual acuity (VA) treatment response
Baseline and 12 months
cpRNFL thickness change over time by visual acuity (VA) treatment response
Baseline and 12 months
- +14 more other outcomes
Study Arms (2)
Arm I (carboplatin, vincristine)
ACTIVE COMPARATORINDUCTION: Patients receive carboplatin IV over 60 minutes on days 1, 8, 15, 22, 43, 50, 57, and 64 and vincristine IV or IV push over 1 minute on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64 in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI throughout the trial. MAINTENANCE: Patients receive carboplatin IV over 60 minutes on days 1, 8, 15, and 22 of each cycle and vincristine IV or IV push over 1 minute on days 1, 8, and 15 of each cycle. Cycles repeat every 6 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI throughout the trial.
Arm II (selumetinib sulfate)
EXPERIMENTALPatients receive selumetinib sulfate PO BID on days 1-28 of each cycle. Treatment is continuous and cycles repeat every 28 days for 27 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI throughout the trial.
Interventions
Given IV
Undergo MRI
Ancillary studies
Ancillary studies
Given PO
Given IV or IV push
Eligibility Criteria
You may qualify if:
- 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 neurofibromatosis type 1 (NF1) based on clinical criteria and/or germline genetic testing
- Patients must be newly diagnosed or have previously diagnosed NF-1 associated LGG that has not been treated with any modality other than surgery
- For patients with optic pathway gliomas (OPGs):
- Newly-diagnosed patients with OPG are eligible if there are neurologic symptoms (including visual dysfunction, as defined below) or other exam findings associated with the tumor
- Previously-diagnosed patients with OPG are eligible if they have new or worsening neurologic symptoms (including visual dysfunction, as defined below) or have tumor growth
- For both newly-diagnosed and previously-diagnosed OPG, the patient may be eligible, irrespective of whether there has been tumor growth or other neurological symptoms or worsening, if they meet at least one of the following visual criteria:
- Visual worsening, defined as worsening of visual acuity (VA) or visual fields (VF) documented within the past year (by examination or history); OR
- Significant visual dysfunction (defined as VA worse than normal for age by 0.6 logMAR \[20/80, 6/24, or 2.5/10\] or more in one or both eyes)
- For patients with LGG in other locations (i.e., not OPGs):
- Newly-diagnosed patients with LGG are eligible if there are neurologic symptoms or other exam findings associated with the tumor
- NOTE: Newly-diagnosed patients with LGG without associated neurologic symptoms or exam findings are not eligible
- Previously-diagnosed patients with LGG are eligible if they have new or worsening neurologic symptoms or have tumor growth
- Although not required, if a biopsy/tumor resection is performed, eligible histologies will include all tumors considered LGG 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
- +29 more criteria
You may not qualify if:
- Patients must not have received any prior tumor-directed therapy including chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant. Prior surgical intervention is permitted
- Patients with a concurrent malignancy or history of treatment (other than surgery) for another tumor within the last year are ineligible
- Patients may not be receiving any other investigational agents
- Patients with any serious medical or psychiatric illness/ condition, including substance use disorders likely in the judgement of the investigator to interfere or limit compliance with study requirements/treatment are not eligible
- 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 12 weeks after stopping study therapy are not eligible
- Note: Women of child-bearing potential and males with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) should use effective methods of contraception for the duration of the study and for 12 weeks after stopping study therapy to avoid pregnancy and/or potential adverse effects on the developing embryo
- Cardiac conditions:
- Symptomatic heart failure
- New York Heart Association (NYHA) class II-IV prior or current cardiomyopathy
- Severe valvular heart disease
- History of atrial fibrillation
- Ophthalmologic conditions:
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (132)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
Banner Children's at Desert
Mesa, Arizona, 85202, United States
Phoenix Childrens Hospital
Phoenix, Arizona, 85016, United States
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591, United States
Loma Linda University Medical Center
Loma Linda, California, 92354, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Kaiser Permanente-Oakland
Oakland, California, 94611, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304, United States
Rady Children's Hospital - San Diego
San Diego, California, 92123, United States
Naval Medical Center -San Diego
San Diego, California, 92134, United States
UCSF Medical Center-Mission Bay
San Francisco, California, 94158, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Connecticut Children's Medical Center
Hartford, Connecticut, 06106, United States
Yale University
New Haven, Connecticut, 06520, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908, United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207, United States
Nicklaus Children's Hospital
Miami, Florida, 33155, United States
AdventHealth Orlando
Orlando, Florida, 32803, United States
Arnold Palmer Hospital for Children
Orlando, Florida, 32806, United States
Nemours Children's Hospital
Orlando, Florida, 32827, United States
Sacred Heart Hospital
Pensacola, Florida, 32504, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329, United States
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611, United States
University of Illinois
Chicago, Illinois, 60612, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Southern Illinois University School of Medicine
Springfield, Illinois, 62702, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
Ascension Saint Vincent Indianapolis Hospital
Indianapolis, Indiana, 46260, United States
Blank Children's Hospital
Des Moines, Iowa, 50309, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Norton Children's Hospital
Louisville, Kentucky, 40202, United States
Children's Hospital New Orleans
New Orleans, Louisiana, 70118, United States
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121, United States
Eastern Maine Medical Center
Bangor, Maine, 04401, United States
Maine Children's Cancer Program
Scarborough, Maine, 04074, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
Children's Hospital of Michigan
Detroit, Michigan, 48201, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503, United States
Corewell Health Children's
Royal Oak, Michigan, 48073, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
University of Missouri Children's Hospital
Columbia, Missouri, 65212, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108, United States
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756, United States
Morristown Medical Center
Morristown, New Jersey, 07960, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903, United States
Presbyterian Hospital
Albuquerque, New Mexico, 87106, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106, United States
Albany Medical Center
Albany, New York, 12208, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, 11040, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
University of Rochester
Rochester, New York, 14642, United States
State University of New York Upstate Medical University
Syracuse, New York, 13210, United States
New York Medical College
Valhalla, New York, 10595, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
East Carolina University
Greenville, North Carolina, 27834, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Sanford Broadway Medical Center
Fargo, North Dakota, 58122, United States
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Dayton Children's Hospital
Dayton, Ohio, 45404, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Legacy Emanuel Children's Hospital
Portland, Oregon, 97227, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Geisinger Medical Center
Danville, Pennsylvania, 17822, United States
Penn State Children's Hospital
Hershey, Pennsylvania, 17033, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
Rhode Island Hospital
Providence, Rhode Island, 02903, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Prisma Health Richland Hospital
Columbia, South Carolina, 29203, United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605, United States
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
El Paso Children's Hospital
El Paso, Texas, 79905, United States
Cook Children's Medical Center
Fort Worth, Texas, 76104, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Covenant Children's Hospital
Lubbock, Texas, 79410, United States
UMC Cancer Center / UMC Health System
Lubbock, Texas, 79415, United States
Children's Hospital of San Antonio
San Antonio, Texas, 78207, United States
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229, United States
Primary Children's Hospital
Salt Lake City, Utah, 84113, United States
University of Vermont and State Agricultural College
Burlington, Vermont, 05405, United States
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
Carilion Children's
Roanoke, Virginia, 24014, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204, United States
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, 98405, United States
Madigan Army Medical Center
Tacoma, Washington, 98431, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4, Canada
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8, Canada
Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, H3H 1P3, Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5, Canada
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
Sherbrooke, Quebec, J1H 5N4, Canada
HIMA San Pablo Oncologic Hospital
Caguas, 00726, Puerto Rico
Related Publications (1)
Bergqvist C, Wolkenstein P. MEK inhibitors in RASopathies. Curr Opin Oncol. 2021 Mar 1;33(2):110-119. doi: 10.1097/CCO.0000000000000711.
PMID: 33395032DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jason R Fangusaro
Children's Oncology Group
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 11, 2019
First Posted
March 12, 2019
Study Start
January 15, 2020
Primary Completion (Estimated)
December 31, 2027
Study Completion (Estimated)
December 31, 2027
Last Updated
April 13, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page