A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma
Start Date
1/31/2020
Completion Date
12/31/2030
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.
Detailed Description
PRIMARY OBJECTIVE: I. To demonstrate that the efficacy of treatment with selumetinib as measured by event-free survival (EFS) is non-inferior compared to treatment with carboplatin/vincristine (CV) in previously-untreated low-grade glioma (LGG) not associated with BRAFV600E mutations or systemic neurofibromatosis type 1 (NF1). SECONDARY OBJECTIVES: I. To estimate tumor response rates to each regimen of chemotherapy. II. To evaluate visual acuity (VA) outcomes utilizing Teller Acuity Cards (TAC) and HOTV letter acuity testing in previously-untreated optic pathway gliomas (OPGs). III. To describe the improvement in motor function as measured by the Vineland Scale in children with previously-untreated LGG that have motor deficits at enrollment. IV. To estimate the difference in EFS and tumor response rate between BRAF rearranged and non-BRAF rearranged patients treated on each chemotherapy regimen. V. To prospectively evaluate the quality of life of children with LGG not associated with BRAFV600E or systemic NF1 treated with either CV or selumetinib. VI. To prospectively evaluate the cognitive, social, emotional, and behavioral functioning of children with LGG not associated with BRAFV600E or systemic NF1 treated with either CV or selumetinib. EXPLORATORY OBJECTIVE: I. To obtain paired blood and tumor specimens for future biology studies as well as data from Molecular Characterization Initiative (MCI) testing, to correlate genomic drivers to efficacy outcomes. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: INDUCTION: Patients receive vincristine sulfate intravenously (IV) on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64, and carboplatin IV over 60 minutes on days 1, 8, 15, 22, 43, 50, 57, and 64 in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and magnetic resonance imaging (MRI) throughout the trial. MAINTENANCE: Patients receive vincristine sulfate IV on days 1, 8, and 15, and carboplatin IV over 60 minutes on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 42 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and MRI throughout the trial. ARM II: Patients receive selumetinib sulfate orally (PO) twice daily (BID) on days 1-28 of each cycle. Cycles repeat every 28 days for up to 27 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo echocardiography (ECHO) at baseline and undergo collection of blood and MRI throughout the trial. After completion of study treatment, patients are followed up every 3 months for year 1, every 6 months for years 2-3, and then annually for years 4-10.
Eligibility Criteria
Age Range: 2 years to 21 years
Interventions
Biospecimen Collection
Carboplatin
Echocardiography Test
Magnetic Resonance Imaging
Questionnaire Administration
Selumetinib Sulfate
Vincristine Sulfate
Conditions
Locations
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
Miller Children's and Women's Hospital Long Beach
Long Beach, California 90806
United States
Children's Hospital Los Angeles
Los Angeles, California 90027
United States
Cedars-Sinai Medical Center
Los Angeles, California 90048
United States
Mattel Children's Hospital UCLA
Los Angeles, California 90095
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
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
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida 33136
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
Nemours Children's Clinic - Pensacola
Pensacola, Florida 32504
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
OSF Children's Hospital of Illinois
Peoria, Illinois 61637
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
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
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
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
Morristown Medical Center
Morristown, New Jersey 07960
United States
Albany Medical Center
Albany, New York 12208
United States
Roswell Park Cancer Institute
Buffalo, New York 14263
United States
NYU Langone Hospital - Long Island
Mineola, New York 11501
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
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
UT MD 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
West Virginia University Healthcare
Morgantown, West Virginia 26506
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
Janeway Child Health Centre
St. John's, Newfoundland and Labrador A1B 3V6
Canada
IWK Health Centre
Halifax, Nova Scotia B3K 6R8
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
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Québec, G1V 4G2
Canada
HIMA San Pablo Oncologic Hospital
Caguas, 00726
Puerto Rico