Low Grade AstrocytomaPhase 3NCT04166409
A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma
A Phase 3 study testing Biospecimen Collection, Carboplatin and Echocardiography Test in people with Low Grade Astrocytoma and Low Grade Glioma, run by National Cancer Institute (NCI) at 132 sites in 3 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 2 to 21 years
- Conditions the study is for
- Low Grade Astrocytoma, Low Grade Glioma, Metastatic Low Grade Astrocytoma
- What is being tested?
- Biospecimen Collection, Carboplatin and Echocardiography Test
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 170 participants
- Where
- 132 sitesin 3 countries
- Study dates
- 31 Jan 2020to 31 Dec 2030
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
132 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
132 sites in 3 countries
United States124 sites, 117 recruiting
- Recruiting
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308
Site Public Contact, 330-543-3193
Erin Wright
- Recruiting
Albany Medical Center
Albany, New York, 12208
Site Public Contact, 518-262-5513
Lauren R. Weintraub
- Recruiting
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
Site Public Contact, 800-865-1125
Andrea T. Franson
- Recruiting
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329
Site Public Contact, 404-785-0232, Olivia.Floyd@choa.org
Jason R. Fangusaro
- Recruiting
Children's Hospital Colorado
Aurora, Colorado, 80045
Site Public Contact, 303-764-5056, josh.b.gordon@nsmtp.kp.org
Jean M. Mulcahy Levy
- Recruiting
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723
Site Public Contact, 512-628-1902, TXAUS-DL-SFCHemonc.research@ascension.org
Shannon M. Cohn
- Recruiting
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Site Public Contact, 410-955-8804, jhcccro@jhmi.edu
Kenneth J. Cohen
- Recruiting
Eastern Maine Medical Center
Bangor, Maine, 04401
Site Public Contact, 207-973-4274
Daniel L. Callaway
- Recruiting
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600
Site Public Contact, 301-319-2100
Allen I. Stering
- Recruiting
Children's Hospital of Alabama
Birmingham, Alabama, 35233
Site Public Contact, 205-638-9285, oncologyresearch@peds.uab.edu
Laura K. Metrock
- Recruiting
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
Site Public Contact, 208-381-2774, eslinget@slhs.org
Martha M. Pacheco
- Active, not recruiting
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
- Active, not recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
- Recruiting
Roswell Park Cancer Institute
Buffalo, New York, 14263
Site Public Contact, 800-767-9355, askroswell@roswellpark.org
Matthew J. Barth
- Recruiting
University of Vermont and State Agricultural College
Burlington, Vermont, 05405
Site Public Contact, 802-656-8990, rpo@uvm.edu
Jessica L. Heath
- Recruiting
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Site Public Contact, 877-668-0683, cancerclinicaltrials@med.unc.edu
David E. Kram
- Recruiting
Medical University of South Carolina
Charleston, South Carolina, 29425
Site Public Contact, 843-792-9321, hcc-clinical-trials@musc.edu
Jacqueline M. Kraveka
- Recruiting
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
Site Public Contact, 800-804-9376
Joel A. Kaplan
- Recruiting
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
Site Public Contact, 773-880-4562
Angela J. Waanders
- Recruiting
University of Illinois
Chicago, Illinois, 60612
Site Public Contact, 312-355-3046
Dipti S. Dighe
- Recruiting
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Site Public Contact, 773-702-8222, cancerclinicaltrials@bsd.uchicago.edu
Wendy S. Darlington
- Recruiting
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Site Public Contact, 513-636-2799, cancer@cchmc.org
Peter M. de Blank
- Recruiting
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106
Site Public Contact, 216-844-5437
Duncan S. Stearns
- Recruiting
Prisma Health Richland Hospital
Columbia, South Carolina, 29203
Site Public Contact, 864-522-4317, Kim.Williams3@prismahealth.org
Stuart L. Cramer
- Recruiting
Nationwide Children's Hospital
Columbus, Ohio, 43205
Site Public Contact, 614-722-6039, Melinda.Triplet@nationwidechildrens.org
Mark A. Ranalli
- Recruiting
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Site Public Contact, 214-648-7097, canceranswerline@UTSouthwestern.edu
Daniel C. Bowers
- Recruiting
Geisinger Medical Center
Danville, Pennsylvania, 17822
Site Public Contact, 570-271-5251, cancerresearch@geisinger.edu
Jagadeesh Ramdas
- Recruiting
Dayton Children's Hospital
Dayton, Ohio, 45404
Site Public Contact, 800-228-4055
Jordan M. Wright
- Recruiting
Blank Children's Hospital
Des Moines, Iowa, 50309
Site Public Contact, 515-241-8912, samantha.mallory@unitypoint.org
Samantha L. Mallory
- Recruiting
Children's Hospital of Michigan
Detroit, Michigan, 48201
Site Public Contact, helpdesk@childrensoncologygroup.org
Stephanie A. Toll
- Recruiting
Duke University Medical Center
Durham, North Carolina, 27710
Site Public Contact, 888-275-3853
Jessica M. Sun
- Recruiting
El Paso Children's Hospital
El Paso, Texas, 79905
Site Public Contact, 915-298-5444, ranjan.bista@ttuhsc.edu
Benjamin Carcamo
- Recruiting
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
Site Public Contact, 701-323-5760, OncologyClinicalTrialsFargo@sanfordhealth.org
Samuel J. Milanovich
- Recruiting
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908
Site Public Contact, 239-343-5333, molly.arnstrom@leehealth.org
Emad K. Salman
- Recruiting
Cook Children's Medical Center
Fort Worth, Texas, 76104
Site Public Contact, 682-885-2103, CookChildrensResearch@cookchildrens.org
Sibo Zhao
- Active, not recruiting
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610
- Recruiting
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503
Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org
Kathleen Y. Butler
- Recruiting
East Carolina University
Greenville, North Carolina, 27834
Site Public Contact, 252-744-1015, eubankss@ecu.edu
Andrea R. Whitfield
- Recruiting
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605
Site Public Contact, 864-522-4317, Kim.Williams3@prismahealth.org
Aniket Saha
- Recruiting
Connecticut Children's Medical Center
Hartford, Connecticut, 06106
Site Public Contact, 860-545-9981
Michael S. Isakoff
- Recruiting
Penn State Children's Hospital
Hershey, Pennsylvania, 17033
Site Public Contact, 717-531-6012
Lisa M. McGregor
- Recruiting
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021
Site Public Contact, 954-265-1847, OHR@mhs.net
Iftikhar Hanif
- Recruiting
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826
Site Public Contact, 808-983-6090
Wade T. Kyono
- Recruiting
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
Site Public Contact, 713-798-1354, burton@bcm.edu
Murali M. Chintagumpala
- Recruiting
UT MD Anderson Cancer Center
Houston, Texas, 77030
Site Public Contact, 866-632-6789, askmdanderson@mdanderson.org
Najat C. Daw
- Recruiting
Riley Hospital for Children
Indianapolis, Indiana, 46202
Site Public Contact, 800-248-1199
Sandeep Batra
- Recruiting
Ascension Saint Vincent Indianapolis Hospital
Indianapolis, Indiana, 46260
Site Public Contact, 317-338-2194, research@stvincent.org
Jessica F. Goodman
- Recruiting
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
Site Public Contact, 800-237-1225
Andrew P. Groves
- Recruiting
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Site Public Contact, 601-815-6700
Amanda Strobel
- Recruiting
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207
Site Public Contact, 302-651-5572, Allison.bruce@nemours.org
Sridhi Patel
- Recruiting
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
Site Public Contact, 816-302-6808, COGResearchGroup@cmh.edu
Keith J. August
- Recruiting
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916
Site Public Contact, 865-541-8266
Susan E. Spiller
- Recruiting
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Site Public Contact, 859-257-3379
James T. Badgett
- Recruiting
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591
Site Public Contact, 501-364-7373
Michael W. Bishop
- Recruiting
Loma Linda University Medical Center
Loma Linda, California, 92354
Site Public Contact, 909-558-4050
Albert Kheradpour
- Recruiting
Miller Children's and Women's Hospital Long Beach
Long Beach, California, 90806
Site Public Contact, 562-933-5600
Jacqueline N. Casillas
- Recruiting
Children's Hospital Los Angeles
Los Angeles, California, 90027
Site Public Contact, 323-361-4110
Nathan J. Robison
- Recruiting
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Site Public Contact, 310-423-2133, Cancer.trial.info@cshs.org
Fataneh (Fae) Majlessipour
- Recruiting
Mattel Children's Hospital UCLA
Los Angeles, California, 90095
Site Public Contact, 310-825-6708
Satiro N. De Oliveira
- Recruiting
Norton Children's Hospital
Louisville, Kentucky, 40202
Site Public Contact, 502-629-5500, CancerResource@nortonhealthcare.org
Michael J. Ferguson
- Recruiting
Covenant Children's Hospital
Lubbock, Texas, 79410
Site Public Contact, 806-725-8657, mbisbee@providence.org
Kishor M. Bhende
- Recruiting
UMC Cancer Center / UMC Health System
Lubbock, Texas, 79415
Site Public Contact, 806-775-8590
Erin K. Barr
- Recruiting
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Site Public Contact, 800-622-8922, clinicaltrials@cancer.wisc.edu
Nicholas J. Pytel
- Recruiting
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105
Site Public Contact, 888-226-4343, referralinfo@stjude.org
Anna Vinitsky
- Recruiting
Banner Children's at Desert
Mesa, Arizona, 85202
Site Public Contact, 480-412-3100
Joseph C. Torkildson
- Withdrawn
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
- Recruiting
Nicklaus Children's Hospital
Miami, Florida, 33155
Site Public Contact, 888-624-2778
Ziad A. Khatib
- Recruiting
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Site Public Contact, 414-955-4727, MACCCTO@mcw.edu
Sarah Rumler
- Recruiting
NYU Langone Hospital - Long Island
Mineola, New York, 11501
Site Public Contact, 212-263-4432, cancertrials@nyulangone.org
Chana L. Glasser
- Recruiting
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404
Site Public Contact, 612-813-5913, pauline.mitby@childrensmn.org
Michael K. Richards
- Recruiting
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455
Site Public Contact, 612-624-2620
Clay M. Hoerig
- Recruiting
West Virginia University Healthcare
Morgantown, West Virginia, 26506
Site Public Contact, 304-293-7374, cancertrialsinfo@hsc.wvu.edu
Ashley E. Meyer
- Recruiting
Morristown Medical Center
Morristown, New Jersey, 07960
Site Public Contact, 973-971-5900
Kathryn L. Laurie
- Recruiting
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Site Public Contact, 800-811-8480
Devang J. Pastakia
- Recruiting
Yale University
New Haven, Connecticut, 06520
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Asher M. Marks
- Recruiting
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, 11040
Site Public Contact, 718-470-3460
Mark P. Atlas
- Recruiting
Children's Hospital New Orleans
New Orleans, Louisiana, 70118
Site Public Contact, 504-894-5377
Maria C. Velez-Yanguas
- Recruiting
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
Site Public Contact, CancerTrials@nyulangone.org
Elizabeth A. Raetz
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Site Public Contact, 212-639-7592
Sameer Farouk Sait
- Recruiting
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507
Site Public Contact, 757-668-7243, CCBDCresearch@chkd.org
Melissa S. Mark
- Recruiting
Kaiser Permanente-Oakland
Oakland, California, 94611
Site Public Contact, 877-642-4691, Kpoct@kp.org
Aarati V. Rao
- Recruiting
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Site Public Contact, 405-271-8777, ou-clinical-trials@ouhsc.edu
Rene Y. McNall-Knapp
- Recruiting
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114
Site Public Contact, 402-955-3949
Jill C. Beck
- Recruiting
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Site Public Contact, 402-559-6941, unmcrsa@unmc.edu
Jill C. Beck
- Recruiting
Children's Hospital of Orange County
Orange, California, 92868
Site Public Contact, 714-509-8646, oncresearch@choc.org
Elyssa M. Rubin
- Recruiting
AdventHealth Orlando
Orlando, Florida, 32803
Site Public Contact, 407-303-2090, FH.Cancer.Research@flhosp.org
Fouad M. Hajjar
- Recruiting
Arnold Palmer Hospital for Children
Orlando, Florida, 32806
Site Public Contact, 321-841-5357, Jennifer.spinelli@orlandohealth.com
Zhongbo Hu
- Recruiting
Nemours Children's Hospital
Orlando, Florida, 32827
Site Public Contact, 302-651-5572, Allison.bruce@nemours.org
Sridhi Patel
- Recruiting
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304
Site Public Contact, 800-694-0012, ccto-office@stanford.edu
Jay Michael S. Balagtas
- Recruiting
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504
Site Public Contact, helpdesk@childrensoncologygroup.org
Jeffrey H. Schwartz
- Suspended
Sacred Heart Hospital
Pensacola, Florida, 32504
- Recruiting
OSF Children's Hospital of Illinois
Peoria, Illinois, 61637
Site Public Contact, 309-624-4945, ChildrensHospitalofIllinois@osfhealthcare.org
Prerna Kumar
- Recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Site Public Contact, 267-425-5544, CancerTrials@email.chop.edu
Michael J. Fisher
- Recruiting
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134
Site Public Contact, 215-427-8991
Gregory E. Halligan
- Recruiting
Phoenix Childrens Hospital
Phoenix, Arizona, 85016
Site Public Contact, 602-546-0920
Kazuhiro Sabet
- Recruiting
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Site Public Contact, 412-692-8570, jean.tersak@chp.edu
James T. Felker
- Recruiting
Oregon Health and Science University
Portland, Oregon, 97239
Site Public Contact, 503-494-1080, trials@ohsu.edu
Neha J. Patel
- Recruiting
Rhode Island Hospital
Providence, Rhode Island, 02903
Site Public Contact, 401-444-1488
Bradley DeNardo
- Recruiting
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
Site Public Contact, 804-628-6430, CTOclinops@vcu.edu
Christopher Park
- Recruiting
Carilion Children's
Roanoke, Virginia, 24014
Site Public Contact, 540-266-6238, wpmccarty@carilionclinic.org
Erwood G. Edwards
- Recruiting
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Site Public Contact, 855-776-0015
Joseph Z. Wilson
- Active, not recruiting
University of Rochester
Rochester, New York, 14642
- Active, not recruiting
Corewell Health Children's
Royal Oak, Michigan, 48073
- Recruiting
Primary Children's Hospital
Salt Lake City, Utah, 84113
Site Public Contact, 801-585-5270
Priya Chan
- Recruiting
Children's Hospital of San Antonio
San Antonio, Texas, 78207
Site Public Contact, 210-704-2894, bridget.medina@christushealth.org
Julie Voeller
- Recruiting
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229
Site Public Contact, 210-575-6240, Vinod.GidvaniDiaz@hcahealthcare.com
Jose M. Esquilin
- Recruiting
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
Site Public Contact, 210-450-3800, phoresearchoffice@uthscsa.edu
Shafqat Shah
- Recruiting
Rady Children's Hospital - San Diego
San Diego, California, 92123
Site Public Contact, 858-966-5934
William D. Roberts
- Recruiting
UCSF Medical Center-Mission Bay
San Francisco, California, 94158
Site Public Contact, 877-827-3222, cancertrials@ucsf.edu
Alyssa T. Reddy
- Recruiting
Maine Children's Cancer Program
Scarborough, Maine, 04074
Site Public Contact, 207-396-8670, clinicalresearch@mainehealth.org
Stanley Chaleff
- Recruiting
Seattle Children's Hospital
Seattle, Washington, 98105
Site Public Contact, 866-987-2000
Sarah E. Leary
- Recruiting
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204
Site Public Contact, 800-228-6618, HopeBeginsHere@providence.org
Judy L. Felgenhauer
- Recruiting
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Site Public Contact, 217-545-7929
Gregory P. Brandt
- Recruiting
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104
Site Public Contact, 314-268-4000
William S. Ferguson
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Andrew S. Cluster
- Recruiting
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701
Site Public Contact, 727-767-4784, Ashley.Repp@jhmi.edu
Stacie L. Stapleton
- Recruiting
State University of New York Upstate Medical University
Syracuse, New York, 13210
Site Public Contact, 315-464-5476
Melanie A. Comito
- Recruiting
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, 98405
Site Public Contact, 253-403-1461, research@multicare.org
Robert G. Irwin
- Recruiting
Madigan Army Medical Center
Tacoma, Washington, 98431
Site Public Contact, 253-968-6144, melissa.a.forouhar.mil@health.mil
Melissa A. Forouhar
- Recruiting
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607
Site Public Contact, 813-357-0849, jennifer.manns@baycare.org
Don E. Eslin
- Recruiting
New York Medical College
Valhalla, New York, 10595
Site Public Contact, 914-594-3794
Andrew J. Bellantoni
- Recruiting
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Site Public Contact, 202-476-2800, OncCRC_OnCall@childrensnational.org
Jeffrey S. Dome
- Recruiting
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803
Site Public Contact, 302-651-5572, Allison.bruce@nemours.org
Sridhi Patel
- Recruiting
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Site Public Contact, 336-713-6771
Sarah Supples
Canada7 sites, 7 recruiting
- Recruiting
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8
Site Public Contact, 902-470-8520, Research@iwk.nshealth.ca
Chelsea Ash
- Recruiting
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, H3H 1P3
Site Public Contact, 514-412-4445, info@thechildren.com
Stephanie Mourad
- Recruiting
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5
Site Public Contact, 514-345-4931, yvan.samson@umontreal.ca
Monia Marzouki
- Recruiting
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Québec, G1V 4G2
Site Public Contact, 418-525-4444, rechclinique@crchudequebec.ulaval.ca
Bruno Michon
- Recruiting
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
Sherbrooke, Quebec, J1H 5N4
Site Public Contact, 819-820-6480, crcinformation.chus@ssss.gouv.qc.ca
Stephanie Vairy
- Recruiting
Janeway Child Health Centre
St. John's, Newfoundland and Labrador, A1B 3V6
Site Public Contact, 709-777-8727, beverlyj.mitchell@easternhealth.ca
Lisa A. Goodyear
- Recruiting
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4
Site Public Contact, 604-875-2345 ext. 6477
Rebecca J. Deyell
Puerto Rico1 site
- Active, not recruiting
HIMA San Pablo Oncologic Hospital
Caguas, 00726
About this study
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)
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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.
- 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:
- 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.
- Conditions
- Low Grade Astrocytoma, Low Grade Glioma, Metastatic Low Grade Astrocytoma, Metastatic Low Grade Glioma, WHO Grade 1 Glioma, WHO Grade 2 Glioma
- Being tested
- Biospecimen Collection, Carboplatin, Echocardiography Test, Magnetic Resonance Imaging, Questionnaire Administration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood sample collection
CarboplatinDrug
Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino
Given IV
Echocardiography TestProcedure or surgery
Also called EC, Echocardiography
Undergo ECHO
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
Questionnaire AdministrationOther
Ancillary studies
Selumetinib SulfateDrug
Also called AZD-6244 Hydrogen Sulfate, AZD6244 Hydrogen Sulfate, AZD6244 Hydrogen Sulphate, Koselugo
Given PO
Also called Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Arm I (vincristine sulfate, carboplatin) | Active comparator | INDUCTION: Patients receive vincristine sulfate 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 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. Receives: Procedure: Biospecimen Collection; Drug: Carboplatin; Procedure: Magnetic Resonance Imaging; Other: Questionnaire Administration; Drug: Vincristine Sulfate |
| Arm II (selumetinib sulfate) | Experimental | Patients receive selumetinib sulfate PO 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 ECHO at baseline and undergo collection of blood and MRI throughout the trial. Receives: Procedure: Biospecimen Collection; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Other: Questionnaire Administration; Drug: Selumetinib Sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free survival (EFS)
The Kaplan-Meier method will be used to estimate EFS which is defined as the interval from randomization to first occurrence of clinical or radiographic disease progression, disease recurrence, second malignant neoplasm, or death from any cause, or to the date of last follow-up. Estimates with 95% confidence intervals will be reported by treatment arm. The hazard ratio with a confidence interval will also be reported to compare treatment arms based on a Cox proportional hazards model stratified by BRAF status, tumor location and size of residual tumor. Will also provide outcome estimates and their associated confidence intervals by sex, race and ethnicity, as descriptive summaries of outcome.
Measured: Up to 10 years from date of randomization
Secondary outcomes (7)
Radiographic tumor response rate
Percentages of patients with responses (complete or partial response) will be reported by treatment arm with 95% confidence intervals. The result of an exact binomial test to test for the difference in response rates between treatment arm will also be reported. Will also provide outcome estimates and their associated confidence intervals by sex, race and ethnicity, as descriptive summaries of outcome.
Measured: Up to 10 years
Overall survival (OS)
The Kaplan-Meier method will be used to estimate OS by treatment arm, defined as the interval from randomization to death from any cause, or to the date of last follow-up. Estimates with confidence intervals will be reported by treatment arm. Will also provide outcome estimates and their associated confidence intervals by sex, race and ethnicity, as descriptive summaries of outcome.
Measured: Up to 10 years from date of randomization
Number of patients who experience an improvement in visual acuity (VA)
Numbers of patients that show improvement in VA after 12 months of treatment will be reported by treatment arm. Patients with at least 1 impaired eye are evaluable. In a patient with a unilateral optic nerve glioma, only the affected eye is considered. In patients with bilateral visual impairment, if VA improves in 1 eye but worsens in the other, the patient will be coded as a treatment failure, whereas if 1 eye improves and the other is at least stable, the patient will be coded as a success.
Measured: After the first 12 months of treatment
Change in motor function
Motor function is measured using the Vineland-3 Motor Scale. Only patients with motor function deficits at baseline are included. Magnitudes of change from baseline between the 2 treatment arms and provide a 90% 2-sided confidence interval for this difference.
Measured: After 48 weeks of therapy
Change in quality of life (QOL)
QOL will be measured using the PedsQL Total Scale Score as measured from the validated PedsQL Generic Module (for children 2-21 years old). Mean differences in the total scale score between 9 months and baseline will be reported by treatment arm. The results of 2-sample t-test comparing differences in the QOL scores between the 2 arms will also be reported. If change scores do not follow normal distributions, non-parametric alternatives may be employed for analysis.
Measured: Baseline and 9 months after treatment initiation
Processing speed function
Measured by Wechsler Processing Speed Index (standard score). Scores at 9 months will be summarized by treatment arm and reported as means (with standard deviations) or medians (with ranges) depending on the data distribution.
Measured: Up to 9 months post-treatment initiation
Change in executive function
Executive function will be measured by the Behavior Rating Inventory of Executive Function, Second Edition BRIEF Cognitive Regulation Index (CRI). Summary statistics for the differences in scores from baseline to 9 months will be reported by treatment arm.
Measured: Baseline and 9-months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2019
- Study start31 Jan 2020
- Primary completion31 Dec 2030 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Low Grade AstrocytomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 170 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Peter M de Blank, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04166409
- Sponsor's protocol ID
- NCI-2019-07600
- Other IDs
- NCI-2019-07600, ACNS1833, ACNS1833, U10CA180886
- Status last verified
- May 2026
- First submitted
- 15 Nov 2019
- Last updated
- 11 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Bergqvist C, Wolkenstein P. MEK inhibitors in RASopathies. Curr Opin Oncol. 2021 Mar 1;33(2):110-119. doi: 10.1097/CCO.0000000000000711.
PubMed 33395032Arnold A, Rodriguez F, Eberhart CG, Raabe EH. Response to letter to the editor: "All models are wrong; some models are useful". Neuro Oncol. 2020 Sep 29;22(9):1406-1407. doi: 10.1093/neuonc/noaa137. No abstract available.
PubMed 32597469