A Study to Compare Treatment With the Drug Selumetinib Alone Versus Selumetinib and Vinblastine in Patients With Recurrent or Progressive Low-Grade Glioma
A Phase 3 Study of Selumetinib (NSC# 748727) or Selumetinib in Combination With Vinblastine for Non-NF1, Non-TSC Patients With Recurrent or Progressive Low-Grade Gliomas (LGGs) Lacking BRAFV600E or IDH1 Mutations
3 other identifiers
interventional
300
2 countries
101
Brief Summary
This phase III trial investigates the best dose of vinblastine in combination with selumetinib and the benefit of adding vinblastine to selumetinib compared to selumetinib alone in treating children and young adults with low-grade glioma (a common type of brain cancer) that has come back after prior treatment (recurrent) or does not respond to therapy (progressive). Selumetinib is a drug that works by blocking a protein that lets tumor cells grow without stopping. Vinblastine blocks cell growth by stopping cell division and may kill cancer cells. Giving selumetinib in combination with vinblastine may work better than selumetinib alone in treating recurrent or progressive low-grade glioma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Feb 2021
Longer than P75 for phase_3
101 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 3, 2020
CompletedFirst Posted
Study publicly available on registry
October 6, 2020
CompletedStudy Start
First participant enrolled
February 16, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 30, 2026
April 13, 2026
February 1, 2026
5.9 years
October 3, 2020
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Maximum tolerated dose/recommended phase II dose (MTD/RP2D) of selumetinib and vinblastine combination (feasibility)
The MTD is empirically defined as the highest dose level at which 6 patients have been treated with at most one patient experiencing a dose-limiting toxicity (DLT) and the next higher dose level has been determined to be too toxic.
1 month post enrollment
Event-free survival (efficacy)
Will use Kaplan-Meier (KM) methods and stratified log-rank tests to estimate EFS per arm and compare the EFS outcome between the two arms to assess difference in efficacy. EFS is defined as the interval from randomization to the first occurrence of clinical or radiographic disease progression, disease recurrence, subsequent malignant neoplasm, or death from any cause. Patients who are event-free will be censored at the time of last follow-up.
Up to 5 years after enrollment
Secondary Outcomes (7)
Radiographic tumor response rate (efficacy)
Up to 2 years after enrollment
Overall survival (OS) (efficacy)
Up to 5 years after enrollment
EFS by BRAF Status
Up to 5 years after enrollment
Incidence of adverse events (feasibility)
Up to 5 years
Incidence of adverse events (efficacy)
Up to 5 years
- +2 more secondary outcomes
Study Arms (2)
Efficacy Phase Arm II (selumetinib)
ACTIVE COMPARATORPatients receive selumetinib sulfate PO BID on days 1-28. Treatment repeats every 28 days for up to 27 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MRI throughout the trial. Patients also undergo blood sample collection during screening and on study.
Feasibility & Efficacy Phase Arm I (selumetinib, vinblastine)
EXPERIMENTALPatients receive vinblastine sulfate IV over 1 minute or IV infusion on days 1, 8, 15, and 22 and selumetinib sulfate PO BID on days 1-28. Treatment repeats every 28 days. Patients receive selumetinib and vinblastine for a total duration of 17 cycles followed by 10 additional cycles of selumetinib alone in the absence of disease progression or unacceptable toxicity. Patients undergo MRI throughout the trial. Patients also undergo blood sample collection during screening and on study.
Interventions
Given PO
Given IV
Undergo blood sample collection
Undergo MRI
Ancillary studies
Ancillary studies
Eligibility Criteria
You may qualify if:
- Feasibility phase: patients must be \>= 2 years and =\< 21 years of age at the time of enrollment
- Efficacy phase: patients must be \>= 2 years and =\< 25 years of age at the time of enrollment
- All patients \> 21 years of age at the time of enrollment must have had initial diagnosis of low-grade glioma by 21 years of age
- Patients must have a body surface area (BSA) of \>= 0.5 m\^2 at enrollment
- Patients must have eligibility confirmed by rapid central pathology and central molecular screening reviews performed on APEC14B1
- Non-neurofibromatosis type 1 (non-NF1), non-tuberous sclerosis complex (non-TSC) low-grade glioma (LGG) without a BRAFV600E or IDH1 mutation
- Patients must have progressive or recurrent LGG. Note: Biopsy may be at either initial diagnosis or recurrence
- Patients must have measurable disease, defined as having a two-dimensional measurable tumor volume of \>= 1 cm\^2
- Tumor size will be measured to include both solid and cystic components of the tumor (whether or not tumor is enhancing) + fluid attenuated inversion recovery (FLAIR) signal
- Eligible histologies will include all tumors considered low-grade glioma or low-grade astrocytoma (World Health Organization \[WHO\] grade 1 and II) by the WHO Classification of Tumors of the Central Nervous System - 4th Edition Revised, with the exception of subependymal giant cell astrocytoma
- Patients with metastatic disease or multiple independent primary LGGs are eligible
- Patients must be progressive or recurrent after having been treated with at least one prior tumor-directed therapy before enrollment
- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
- Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry onto this study (4 weeks if prior nitrosourea);
- Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent;
- +29 more criteria
You may not qualify if:
- Prior therapy with vinblastine and/or a MEK inhibitor is permitted, with the following exceptions:
- Patients must not have had progressive disease while on therapy with vinblastine or a MEK inhibitor;
- Patients must not have discontinued vinblastine or selumetinib due to toxicity
- 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 must not have known hypersensitivity to selumetinib, vinblastine, or similar compounds
- CYP3A4 agents: Patients must not have received fluconazole or drugs that are strong inducers or inhibitors of CYP3A4 within 7 days prior to study enrollment
- 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
- PRE-EXISTING CONDITIONS (CARDIAC):
- Symptomatic heart failure
- New York Heart Association (NYHA) class II-IV prior or current cardiomyopathy
- Severe valvular heart disease
- History of atrial fibrillation
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (101)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, 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
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
Arnold Palmer Hospital for Children
Orlando, Florida, 32806, United States
Nemours Children's Hospital
Orlando, Florida, 32827, 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
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
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
Ascension Saint Vincent Indianapolis Hospital
Indianapolis, Indiana, 46260, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
Norton Children's Hospital
Louisville, Kentucky, 40202, United States
Children's Hospital New Orleans
New Orleans, Louisiana, 70118, 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
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
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903, 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
State University of New York Upstate Medical University
Syracuse, New York, 13210, United States
New York Medical College
Valhalla, New York, 10595, 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
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
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
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
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
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
Children's Hospital of San Antonio
San Antonio, Texas, 78207, 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
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, 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
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
University of Alberta Hospital
Edmonton, Alberta, T6G 2B7, Canada
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4, Canada
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9, Canada
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8, Canada
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1, 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
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Québec, G1V 4G2, Canada
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Daniel C Bowers
Children's Oncology Group
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 3, 2020
First Posted
October 6, 2020
Study Start
February 16, 2021
Primary Completion (Estimated)
December 30, 2026
Study Completion (Estimated)
December 30, 2026
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.