MEK inhibitors in RASopathies.
Christina Bergqvist, Pierre Wolkenstein
https://pubmed.ncbi.nlm.nih.gov/33395032Actively Recruiting
Phase 3
Age: 2Years - 21Years
All Genders
ID04166409
A Phase 3 Randomized Non-Inferiority Study of Carboplatin and Vincristine Versus Selumetinib in Newly Diagnosed or Previously Untreated Low-Grade Glioma Not Associated With BRAFV600E Mutations or Systemic Neurofibromatosis Type 1
Led by National Cancer Institute (NCI) · Updated on 2026-05-29
170
Participants Needed
132
Research Sites
N/A
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the effects of selumetinib compared to the standard treatment with carboplatin and vincristine for patients with newly diagnosed or previously untreated low-grade glioma (LGG) that lacks the BRAFV600E mutation and is not linked to systemic neurofibromatosis type 1. This phase III trial aims to determine if selumetinib is as effective as the standard chemotherapy regimen and to assess which treatment may be better, including their impact on patients' quality of life. Participants are randomly assigned to one of two groups. In the first group, patients receive vincristine sulfate intravenously on specific days during an induction phase, combined with carboplatin given intravenously over 60 minutes on certain days, followed by a maintenance phase with repeated cycles of these drugs. In the second group, patients take selumetinib sulfate orally twice daily in 28-day cycles for up to 27 cycles, with echocardiography performed at the start of treatment. Blood samples and MRI scans are collected throughout the study for monitoring. During the study, patients undergo regular assessments including MRI scans to monitor tumor status, blood tests, and quality of life evaluations. Follow-up visits occur every three months during the first year, every six months for years two and three, and annually for up to ten years after treatment completion. The main outcome measured is event-free survival up to ten years following randomization, along with secondary outcomes like tumor response, visual acuity, motor function, cognitive and behavioral functioning, and overall survival. Safety and treatment effects are closely monitored throughout the trial.
CONDITIONS
Brief Title
A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma
Who Can Participate
Age: 2Years - 21Years
All Genders
Eligibility Criteria
You may qualify if you...
- Patients aged 2 to 21 years at enrollment
- Body surface area (BSA) of at least 0.5 m²
- Non-neurofibromatosis type 1 low-grade glioma (LGG) without BRAFV600E mutation confirmed by accepted testing
- Newly diagnosed or previously diagnosed with no prior chemotherapy or radiation treatment
- Two-dimensional measurable tumor of at least 1 cm²
- Eligible histologies include WHO grade I and II low-grade gliomas excluding subependymal giant cell astrocytoma
- Patients with metastatic disease or multiple independent primary LGG are eligible
- Adequate kidney function (creatinine clearance or GFR ≥ 70 mL/min/1.73 m² or age/sex-based serum creatinine within 7 days prior to enrollment)
- Total bilirubin ≤ 1.5 times upper limit of normal for age
- Serum glutamic pyruvic transaminase (SGPT/ALT) ≤ 135 U/L
- Albumin ≥ 2 g/dL
- Left ventricular ejection fraction (LVEF) ≥ 53% by echocardiogram within 4 weeks prior to enrollment
- Corrected QT interval ≤ 450 msec by EKG within 4 weeks prior to enrollment
- Absolute neutrophil count ≥ 1,000/uL and platelets ≥ 100,000/uL within 7 days prior to enrollment
- Hemoglobin ≥ 8 g/dL within 7 days prior to enrollment
- Stable seizure disorder without recent increase in frequency
- Blood pressure ≤ 95th percentile for age, height, and sex (ages 2-17) or ≤ 130/80 mmHg (≥18 years), with or without medication
- Ophthalmology toxicity assessments within 8 weeks prior to enrollment
- MRI of brain and/or spine with and without contrast within 8 weeks prior to enrollment
- Performance status ECOG 0-2 (Karnofsky or Lansky scores as appropriate)
- Ability to swallow whole capsules
- Signed informed consent and met all institutional and regulatory requirements
- Enrollment on APEC14B1 for pre-enrollment eligibility screening
You will not qualify if you...
- Prior tumor-directed therapy including chemotherapy, radiation, immunotherapy, or bone marrow transplant
- History of treatment for another tumor in the past year except surgery
- Diffuse intrinsic pontine tumors involving more than two-thirds of the pons
- Receiving other investigational agents
- Serious medical or psychiatric illness likely to interfere with study compliance
- Inability to comply with study procedures
- Pregnant or breastfeeding females
- Sexually active patients not agreeing to use effective contraception during and for 1 week after study therapy
- Known genetic disorder increasing coronary artery disease risk
- Symptomatic heart failure or history of cardiomyopathy NYHA class II-IV
- Severe valvular heart disease or history of atrial fibrillation
- History or presence of central serous retinopathy, retinal vein occlusion, retinal detachment, or uncontrolled glaucoma
- Elevated intraocular pressure over age-adjusted limits
- Use of vitamin E supplements greater than 100% of recommended daily dose
- Surgery within 2 weeks prior to enrollment except specified procedures with healed wounds
- Uncontrolled infection
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
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3
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - Induction and maintenance cycles up to approximately 10 months for vincristine and carboplatin; up to 27 cycles of 28 days for selumetinib (approximately 27 months) in the absence of disease progression or unacceptable toxicity.
Participants receive one of two treatments: either vincristine sulfate and carboplatin through intravenous infusions in induction and maintenance phases or selumetinib sulfate orally twice daily in repeated cycles. Blood samples and MRI scans are collected throughout treatment, with baseline echocardiography for those receiving selumetinib.
Multiple visits for IV drug administration and monitoring during induction and maintenance for vincristine and carboplatin; regular visits for oral selumetinib cycles and assessments including baseline ECHO
Follow-up
Duration - Up to 10 years from date of randomization
After completing treatment, participants are monitored for long-term outcomes including event-free survival, tumor response, visual acuity, motor function, quality of life, and cognitive function.
Every 3 months for year 1, every 6 months for years 2-3, then annually for years 4-10
Trial Site Locations
Total: 132 locations
1
Children's Hospital of Alabama
Birmingham, Alabama, United States, 35233
Actively Recruiting
2
Banner Children's at Desert
Mesa, Arizona, United States, 85202
Actively Recruiting
3
Phoenix Childrens Hospital
Phoenix, Arizona, United States, 85016
Actively Recruiting
4
Arkansas Children's Hospital
Little Rock, Arkansas, United States, 72202-3591
Actively Recruiting
5
Loma Linda University Medical Center
Loma Linda, California, United States, 92354
Actively Recruiting
6
Miller Children's and Women's Hospital Long Beach
Long Beach, California, United States, 90806
Actively Recruiting
7
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Actively Recruiting
8
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Actively Recruiting
9
Mattel Children's Hospital UCLA
Los Angeles, California, United States, 90095
Actively Recruiting
10
Kaiser Permanente-Oakland
Oakland, California, United States, 94611
Actively Recruiting
11
Children's Hospital of Orange County
Orange, California, United States, 92868
Actively Recruiting
12
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States, 94304
Actively Recruiting
13
Rady Children's Hospital - San Diego
San Diego, California, United States, 92123
Actively Recruiting
14
UCSF Medical Center-Mission Bay
San Francisco, California, United States, 94158
Actively Recruiting
15
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
Actively Recruiting
16
Connecticut Children's Medical Center
Hartford, Connecticut, United States, 06106
Actively Recruiting
17
Yale University
New Haven, Connecticut, United States, 06520
Actively Recruiting
18
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States, 19803
Actively Recruiting
19
Children's National Medical Center
Washington D.C., District of Columbia, United States, 20010
Actively Recruiting
20
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, United States, 33908
Actively Recruiting
21
UF Health Cancer Institute - Gainesville
Gainesville, Florida, United States, 32610
Active, Not Recruiting
22
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, United States, 33021
Actively Recruiting
23
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, United States, 32207
Actively Recruiting
24
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States, 33136
Withdrawn
25
Nicklaus Children's Hospital
Miami, Florida, United States, 33155
Actively Recruiting
26
AdventHealth Orlando
Orlando, Florida, United States, 32803
Actively Recruiting
27
Arnold Palmer Hospital for Children
Orlando, Florida, United States, 32806
Actively Recruiting
28
Nemours Children's Hospital
Orlando, Florida, United States, 32827
Actively Recruiting
29
Nemours Children's Clinic - Pensacola
Pensacola, Florida, United States, 32504
Actively Recruiting
30
Sacred Heart Hospital
Pensacola, Florida, United States, 32504
Suspended
31
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States, 33701
Actively Recruiting
32
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, United States, 33607
Actively Recruiting
33
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, United States, 30329
Actively Recruiting
34
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, United States, 96826
Actively Recruiting
35
Saint Luke's Cancer Institute - Boise
Boise, Idaho, United States, 83712
Actively Recruiting
36
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States, 60611
Actively Recruiting
37
University of Illinois
Chicago, Illinois, United States, 60612
Actively Recruiting
38
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637
Actively Recruiting
39
OSF Children's Hospital of Illinois
Peoria, Illinois, United States, 61637
Actively Recruiting
40
Southern Illinois University School of Medicine
Springfield, Illinois, United States, 62702
Actively Recruiting
41
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
Actively Recruiting
42
Ascension Saint Vincent Indianapolis Hospital
Indianapolis, Indiana, United States, 46260
Actively Recruiting
43
Blank Children's Hospital
Des Moines, Iowa, United States, 50309
Actively Recruiting
44
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States, 52242
Actively Recruiting
45
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States, 40536
Actively Recruiting
46
Norton Children's Hospital
Louisville, Kentucky, United States, 40202
Actively Recruiting
47
Children's Hospital New Orleans
New Orleans, Louisiana, United States, 70118
Actively Recruiting
48
Eastern Maine Medical Center
Bangor, Maine, United States, 04401
Actively Recruiting
49
Maine Children's Cancer Program
Scarborough, Maine, United States, 04074
Actively Recruiting
50
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States, 21287
Actively Recruiting
51
Walter Reed National Military Medical Center
Bethesda, Maryland, United States, 20889-5600
Actively Recruiting
52
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
Active, Not Recruiting
53
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Active, Not Recruiting
54
C S Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109
Actively Recruiting
55
Children's Hospital of Michigan
Detroit, Michigan, United States, 48201
Actively Recruiting
56
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, United States, 49503
Actively Recruiting
57
Corewell Health Children's
Royal Oak, Michigan, United States, 48073
Active, Not Recruiting
58
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States, 55404
Actively Recruiting
59
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, United States, 55455
Actively Recruiting
60
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Actively Recruiting
61
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
Actively Recruiting
62
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States, 64108
Actively Recruiting
63
Cardinal Glennon Children's Medical Center
St Louis, Missouri, United States, 63104
Actively Recruiting
64
Washington University School of Medicine
St Louis, Missouri, United States, 63110
Actively Recruiting
65
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, United States, 68114
Actively Recruiting
66
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
Actively Recruiting
67
Morristown Medical Center
Morristown, New Jersey, United States, 07960
Actively Recruiting
68
Albany Medical Center
Albany, New York, United States, 12208
Actively Recruiting
69
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Actively Recruiting
70
NYU Langone Hospital - Long Island
Mineola, New York, United States, 11501
Actively Recruiting
71
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, United States, 11040
Actively Recruiting
72
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, United States, 10016
Actively Recruiting
73
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Actively Recruiting
74
University of Rochester
Rochester, New York, United States, 14642
Active, Not Recruiting
75
State University of New York Upstate Medical University
Syracuse, New York, United States, 13210
Actively Recruiting
76
New York Medical College
Valhalla, New York, United States, 10595
Actively Recruiting
77
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States, 27599
Actively Recruiting
78
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, United States, 28203
Actively Recruiting
79
Duke University Medical Center
Durham, North Carolina, United States, 27710
Actively Recruiting
80
East Carolina University
Greenville, North Carolina, United States, 27834
Actively Recruiting
81
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
Actively Recruiting
82
Sanford Broadway Medical Center
Fargo, North Dakota, United States, 58122
Actively Recruiting
83
Children's Hospital Medical Center of Akron
Akron, Ohio, United States, 44308
Actively Recruiting
84
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Actively Recruiting
85
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, United States, 44106
Actively Recruiting
86
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
Actively Recruiting
87
Dayton Children's Hospital
Dayton, Ohio, United States, 45404
Actively Recruiting
88
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
Actively Recruiting
89
Oregon Health and Science University
Portland, Oregon, United States, 97239
Actively Recruiting
90
Geisinger Medical Center
Danville, Pennsylvania, United States, 17822
Actively Recruiting
91
Penn State Children's Hospital
Hershey, Pennsylvania, United States, 17033
Actively Recruiting
92
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Actively Recruiting
93
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, United States, 19134
Actively Recruiting
94
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
Actively Recruiting
95
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
Actively Recruiting
96
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Actively Recruiting
97
Prisma Health Richland Hospital
Columbia, South Carolina, United States, 29203
Actively Recruiting
98
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, United States, 29605
Actively Recruiting
99
East Tennessee Childrens Hospital
Knoxville, Tennessee, United States, 37916
Actively Recruiting
100
Saint Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Actively Recruiting
101
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States, 37232
Actively Recruiting
102
Dell Children's Medical Center of Central Texas
Austin, Texas, United States, 78723
Actively Recruiting
103
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, United States, 75390
Actively Recruiting
104
El Paso Children's Hospital
El Paso, Texas, United States, 79905
Actively Recruiting
105
Cook Children's Medical Center
Fort Worth, Texas, United States, 76104
Actively Recruiting
106
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, United States, 77030
Actively Recruiting
107
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Actively Recruiting
108
Covenant Children's Hospital
Lubbock, Texas, United States, 79410
Actively Recruiting
109
UMC Cancer Center / UMC Health System
Lubbock, Texas, United States, 79415
Actively Recruiting
110
Children's Hospital of San Antonio
San Antonio, Texas, United States, 78207
Actively Recruiting
111
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States, 78229
Actively Recruiting
112
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229
Actively Recruiting
113
Primary Children's Hospital
Salt Lake City, Utah, United States, 84113
Actively Recruiting
114
University of Vermont and State Agricultural College
Burlington, Vermont, United States, 05405
Actively Recruiting
115
Children's Hospital of The King's Daughters
Norfolk, Virginia, United States, 23507
Actively Recruiting
116
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, United States, 23298
Actively Recruiting
117
Carilion Children's
Roanoke, Virginia, United States, 24014
Actively Recruiting
118
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Actively Recruiting
119
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, United States, 99204
Actively Recruiting
120
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, United States, 98405
Actively Recruiting
121
Madigan Army Medical Center
Tacoma, Washington, United States, 98431
Actively Recruiting
122
West Virginia University Healthcare
Morgantown, West Virginia, United States, 26506
Actively Recruiting
123
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, United States, 53792
Actively Recruiting
124
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Actively Recruiting
125
British Columbia Children's Hospital
Vancouver, British Columbia, Canada, V6H 3V4
Actively Recruiting
126
Janeway Child Health Centre
St. John's, Newfoundland and Labrador, Canada, A1B 3V6
Actively Recruiting
127
IWK Health Centre
Halifax, Nova Scotia, Canada, B3K 6R8
Actively Recruiting
128
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, Canada, H3H 1P3
Actively Recruiting
129
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, Canada, H3T 1C5
Actively Recruiting
130
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
Sherbrooke, Quebec, Canada, J1H 5N4
Actively Recruiting
131
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Québec, Canada, G1V 4G2
Actively Recruiting
132
HIMA San Pablo Oncologic Hospital
Caguas, Puerto Rico, 00726
Active, Not Recruiting
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How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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Published Research Related To This Trial
Response to letter to the editor: "All models are wrong; some models are useful".
Antje Arnold, Fausto Rodriguez, Charles G Eberhart...
https://pubmed.ncbi.nlm.nih.gov/32597469