A Phase 3 Randomized Study of Selumetinib Versus Carboplatin/Vincristine in Newly Diagnosed or Previously Untreated Neurofibromatosis Type 1 (NF1) Associated Low-Grade Glioma (LGG)

Who is this study for? Patients with Glioma, Neurofibromatosis
Status: Recruiting
Location: See all (129) locations...
Intervention Type: Other, Procedure, Drug
Study Type: Interventional
Study Phase: Phase 3
SUMMARY

This phase III trial studies if selumetinib works just as well as the standard treatment with carboplatin/vincristine (CV) for subjects with NF1-associated low grade glioma (LGG), and to see if selumetinib is better than CV in improving vision in subjects with LGG of the optic pathway (vision nerves). Selumetinib is a drug that works by blocking some enzymes that low-grade glioma tumor cells need for their growth. This results in killing tumor cells. Drugs used as chemotherapy, such as carboplatin and vincristine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether selumetinib works better in treating patients with NF1-associated low-grade glioma compared to standard therapy with carboplatin and vincristine.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 2
Maximum Age: 21
Healthy Volunteers: f
View:

• Patients must be \>= 2 years and =\< 21 years at the time of enrollment

• Patients must have a body surface area (BSA) of \>= 0.5 m\^2 at enrollment

• Patients must have neurofibromatosis type 1 (NF1) based on clinical criteria and/or germline genetic testing

• Patients must be newly diagnosed or have previously diagnosed NF-1 associated LGG that has not been treated with any modality other than surgery

• For patients with optic pathway gliomas (OPGs):

‣ Newly-diagnosed patients with OPG are eligible if there are neurologic symptoms (including visual dysfunction, as defined below) or other exam findings associated with the tumor

⁃ Previously-diagnosed patients with OPG are eligible if they have new or worsening neurologic symptoms (including visual dysfunction, as defined below) or have tumor growth

⁃ For both newly-diagnosed and previously-diagnosed OPG, the patient may be eligible, irrespective of whether there has been tumor growth or other neurological symptoms or worsening, if they meet at least one of the following visual criteria:

• Visual worsening, defined as worsening of visual acuity (VA) or visual fields (VF) documented within the past year (by examination or history); OR

∙ Significant visual dysfunction (defined as VA worse than normal for age by 0.6 logMAR \[20/80, 6/24, or 2.5/10\] or more in one or both eyes)

• For patients with LGG in other locations (i.e., not OPGs):

‣ Newly-diagnosed patients with LGG are eligible if there are neurologic symptoms or other exam findings associated with the tumor

• NOTE: Newly-diagnosed patients with LGG without associated neurologic symptoms or exam findings are not eligible

⁃ Previously-diagnosed patients with LGG are eligible if they have new or worsening neurologic symptoms or have tumor growth

• Although not required, if a biopsy/tumor resection is performed, eligible histologies will include all tumors considered LGG or low-grade astrocytoma (World Health Organization \[WHO\] grade I and II) by 5th edition WHO classification of central nervous system (CNS) tumors with the exception of subependymal giant cell astrocytoma

• Patients must have two-dimensional measurable tumor \>= 1 cm\^2

• Patients with metastatic disease or multiple independent primary LGGs are allowed on study

• Creatinine clearance or radioisotope glomerular filtration Rate (GFR) \>= 70 mL/min/1.73 m\^2 OR a serum creatinine based on age/gender (within 7 days prior to enrollment) as follows:

‣ Age; maximum serum creatinine (mg/dL)

⁃ 2 to \< 6 years; 0.8 (male) and 0.8 (female)

⁃ \>= 16 years; 1.7 (male) and 1.4 (female)

• Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (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 glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 3 x upper limit of normal (ULN) = 135 U/L (within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L

• Albumin \>= 2 g/dL (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 (within 4 weeks prior to enrollment)

• Corrected QT (QTc) interval =\< 450 msec by electrocardiography (EKG) (within 4 weeks prior to enrollment)

• Absolute neutrophil count \>= 1,000/uL (unsupported) (within 7 days prior to enrollment)

• Platelets \>= 100,000/uL (unsupported) (within 7 days prior to enrollment)

• Hemoglobin \>= 8 g/dL (may be supported) (within 7 days prior to enrollment)

• Patients with a known seizure disorder should be stable and should have not 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 gender at the time of enrollment. Patients \>= 18 years of age must have a blood pressure =\< 130/80 mmHg at the time of enrollment (with or without the use of antihypertensive medications).

‣ Note: Adequate blood pressure can be achieved using medication for the treatment of hypertension

• All patients must have ophthalmology toxicity assessments performed within 4 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 4 weeks prior to enrollment

• For patients who undergo a surgery on the target tumor (not required), a pre- and post-operative\* MRI of the brain (with orbital cuts for optic pathway tumors) or spine (depending on the site(s) of primary disease) with and without contrast must also be performed within 4 weeks prior to enrollment

‣ The post-operative MRIs should be performed ideally within 48 hours after surgery if possible

• 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

• Patients must have receptive and expressive language skills in English or Spanish to complete the quality of life (QOL) and neurocognitive assessments

• 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.

Locations
United States
Alabama
Children's Hospital of Alabama
RECRUITING
Birmingham
Arkansas
Arkansas Children's Hospital
RECRUITING
Little Rock
Arizona
Banner Children's at Desert
RECRUITING
Mesa
Phoenix Childrens Hospital
RECRUITING
Phoenix
California
Loma Linda University Medical Center
RECRUITING
Loma Linda
Children's Hospital Los Angeles
RECRUITING
Los Angeles
Kaiser Permanente-Oakland
RECRUITING
Oakland
Children's Hospital of Orange County
RECRUITING
Orange
Lucile Packard Children's Hospital Stanford University
RECRUITING
Palo Alto
Naval Medical Center -San Diego
RECRUITING
San Diego
Rady Children's Hospital - San Diego
RECRUITING
San Diego
UCSF Medical Center-Mission Bay
RECRUITING
San Francisco
Colorado
Children's Hospital Colorado
RECRUITING
Aurora
Connecticut
Connecticut Children's Medical Center
RECRUITING
Hartford
Yale University
RECRUITING
New Haven
Washington, D.c.
Children's National Medical Center
RECRUITING
Washington
Delaware
Alfred I duPont Hospital for Children
RECRUITING
Wilmington
Florida
University of Florida Health Science Center - Gainesville
ACTIVE_NOT_RECRUITING
Gainesville
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
RECRUITING
Hollywood
Nemours Children's Clinic-Jacksonville
RECRUITING
Jacksonville
Nicklaus Children's Hospital
RECRUITING
Miami
AdventHealth Orlando
RECRUITING
Orlando
Arnold Palmer Hospital for Children
RECRUITING
Orlando
Nemours Children's Hospital
RECRUITING
Orlando
Sacred Heart Hospital
RECRUITING
Pensacola
Johns Hopkins All Children's Hospital
RECRUITING
Saint Petersburg
Georgia
Children's Healthcare of Atlanta - Arthur M Blank Hospital
RECRUITING
Atlanta
Hawaii
Kapiolani Medical Center for Women and Children
RECRUITING
Honolulu
Iowa
Blank Children's Hospital
RECRUITING
Des Moines
University of Iowa/Holden Comprehensive Cancer Center
RECRUITING
Iowa City
Idaho
Saint Luke's Cancer Institute - Boise
RECRUITING
Boise
Illinois
Lurie Children's Hospital-Chicago
RECRUITING
Chicago
University of Chicago Comprehensive Cancer Center
RECRUITING
Chicago
University of Illinois
RECRUITING
Chicago
Southern Illinois University School of Medicine
RECRUITING
Springfield
Indiana
Ascension Saint Vincent Indianapolis Hospital
RECRUITING
Indianapolis
Riley Hospital for Children
RECRUITING
Indianapolis
Kentucky
University of Kentucky/Markey Cancer Center
RECRUITING
Lexington
Norton Children's Hospital
RECRUITING
Louisville
Louisiana
Children's Hospital New Orleans
RECRUITING
New Orleans
Ochsner Medical Center Jefferson
RECRUITING
New Orleans
Massachusetts
Dana-Farber Cancer Institute
RECRUITING
Boston
Massachusetts General Hospital Cancer Center
RECRUITING
Boston
Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center
RECRUITING
Baltimore
Walter Reed National Military Medical Center
ACTIVE_NOT_RECRUITING
Bethesda
Maine
Eastern Maine Medical Center
RECRUITING
Bangor
Maine Children's Cancer Program
RECRUITING
Scarborough
Michigan
C S Mott Children's Hospital
RECRUITING
Ann Arbor
Children's Hospital of Michigan
RECRUITING
Detroit
Wayne State University/Karmanos Cancer Institute
SUSPENDED
Detroit
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
RECRUITING
Grand Rapids
Corewell Health Children's
ACTIVE_NOT_RECRUITING
Royal Oak
Minnesota
Children's Hospitals and Clinics of Minnesota - Minneapolis
RECRUITING
Minneapolis
University of Minnesota/Masonic Cancer Center
RECRUITING
Minneapolis
Mayo Clinic in Rochester
RECRUITING
Rochester
Missouri
University of Missouri Children's Hospital
RECRUITING
Columbia
Children's Mercy Hospitals and Clinics
RECRUITING
Kansas City
Cardinal Glennon Children's Medical Center
RECRUITING
Saint Louis
Washington University School of Medicine
RECRUITING
Saint Louis
Mississippi
University of Mississippi Medical Center
RECRUITING
Jackson
North Carolina
UNC Lineberger Comprehensive Cancer Center
RECRUITING
Chapel Hill
Carolinas Medical Center/Levine Cancer Institute
RECRUITING
Charlotte
Duke University Medical Center
RECRUITING
Durham
East Carolina University
RECRUITING
Greenville
Wake Forest University Health Sciences
RECRUITING
Winston-salem
North Dakota
Sanford Broadway Medical Center
RECRUITING
Fargo
Nebraska
Children's Hospital and Medical Center of Omaha
RECRUITING
Omaha
University of Nebraska Medical Center
RECRUITING
Omaha
New Hampshire
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
RECRUITING
Lebanon
New Jersey
Morristown Medical Center
RECRUITING
Morristown
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
RECRUITING
New Brunswick
New Mexico
Presbyterian Hospital
RECRUITING
Albuquerque
University of New Mexico Cancer Center
RECRUITING
Albuquerque
New York
Albany Medical Center
RECRUITING
Albany
Roswell Park Cancer Institute
RECRUITING
Buffalo
The Steven and Alexandra Cohen Children's Medical Center of New York
RECRUITING
New Hyde Park
Laura and Isaac Perlmutter Cancer Center at NYU Langone
RECRUITING
New York
Memorial Sloan Kettering Cancer Center
ACTIVE_NOT_RECRUITING
New York
University of Rochester
RECRUITING
Rochester
State University of New York Upstate Medical University
RECRUITING
Syracuse
New York Medical College
RECRUITING
Valhalla
Ohio
Children's Hospital Medical Center of Akron
RECRUITING
Akron
Cincinnati Children's Hospital Medical Center
RECRUITING
Cincinnati
Rainbow Babies and Childrens Hospital
RECRUITING
Cleveland
Nationwide Children's Hospital
RECRUITING
Columbus
Dayton Children's Hospital
RECRUITING
Dayton
Oklahoma
University of Oklahoma Health Sciences Center
RECRUITING
Oklahoma City
Oregon
Legacy Emanuel Children's Hospital
RECRUITING
Portland
Oregon Health and Science University
RECRUITING
Portland
Pennsylvania
Geisinger Medical Center
RECRUITING
Danville
Penn State Children's Hospital
RECRUITING
Hershey
Children's Hospital of Philadelphia
RECRUITING
Philadelphia
Saint Christopher's Hospital for Children
RECRUITING
Philadelphia
Children's Hospital of Pittsburgh of UPMC
RECRUITING
Pittsburgh
Rhode Island
Rhode Island Hospital
RECRUITING
Providence
South Carolina
Medical University of South Carolina
RECRUITING
Charleston
Prisma Health Richland Hospital
RECRUITING
Columbia
BI-LO Charities Children's Cancer Center
RECRUITING
Greenville
Tennessee
East Tennessee Childrens Hospital
RECRUITING
Knoxville
Saint Jude Children's Research Hospital
RECRUITING
Memphis
Vanderbilt University/Ingram Cancer Center
RECRUITING
Nashville
Texas
Dell Children's Medical Center of Central Texas
RECRUITING
Austin
UT Southwestern/Simmons Cancer Center-Dallas
RECRUITING
Dallas
El Paso Children's Hospital
RECRUITING
El Paso
Cook Children's Medical Center
RECRUITING
Fort Worth
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
RECRUITING
Houston
M D Anderson Cancer Center
RECRUITING
Houston
Covenant Children's Hospital
RECRUITING
Lubbock
UMC Cancer Center / UMC Health System
RECRUITING
Lubbock
Children's Hospital of San Antonio
RECRUITING
San Antonio
Methodist Children's Hospital of South Texas
RECRUITING
San Antonio
University of Texas Health Science Center at San Antonio
RECRUITING
San Antonio
Utah
Primary Children's Hospital
RECRUITING
Salt Lake City
Virginia
Children's Hospital of The King's Daughters
RECRUITING
Norfolk
Virginia Commonwealth University/Massey Cancer Center
RECRUITING
Richmond
Carilion Children's
RECRUITING
Roanoke
Vermont
University of Vermont and State Agricultural College
RECRUITING
Burlington
Washington
Seattle Children's Hospital
RECRUITING
Seattle
Providence Sacred Heart Medical Center and Children's Hospital
RECRUITING
Spokane
Madigan Army Medical Center
RECRUITING
Tacoma
Mary Bridge Children's Hospital and Health Center
RECRUITING
Tacoma
Wisconsin
University of Wisconsin Carbone Cancer Center - University Hospital
RECRUITING
Madison
Children's Hospital of Wisconsin
RECRUITING
Milwaukee
Other Locations
Canada
IWK Health Centre
RECRUITING
Halifax
Centre Hospitalier Universitaire Sainte-Justine
RECRUITING
Montreal
The Montreal Children's Hospital of the MUHC
RECRUITING
Montreal
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
RECRUITING
Sherbrooke
Hospital for Sick Children
RECRUITING
Toronto
Puerto Rico
HIMA San Pablo Oncologic Hospital
SUSPENDED
Caguas
Time Frame
Start Date: 2020-01-15
Estimated Completion Date: 2027-05-01
Participants
Target number of participants: 290
Treatments
Active_comparator: Arm I (carboplatin, vincristine)
INDUCTION: Patients receive carboplatin IV over 60 minutes on days 1, 8, 15, 22, 43, 50, 57, and 64 and vincristine IV or IV push over 1 minute on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64 in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI during screening and on study.~MAINTENANCE: Patients receive carboplatin IV over 60 minutes on days 1, 8, 15, and 22 and vincristine IV or IV push over 1 minute on days 1, 8, and 15. Treatment repeats every 6 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI on study and during follow-up.
Experimental: Arm II (selumetinib sulfate)
Patients receive selumetinib sulfate PO BID on days 1-28. Treatment is continuous and repeats every 28 days for 27 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI throughout the trial.
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov