New drug combo shows promise for kids with aggressive brain tumors

NCT ID NCT03919071

Disease control Sponsor: National Cancer Institute (NCI) Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Jul 10, 2026 · Updated 1 time

Summary

This phase 2 trial tests whether two targeted drugs, dabrafenib and trametinib, can improve outcomes for children and young adults with a specific type of high-grade glioma (BRAF V600-mutant) after they receive radiation therapy. The study enrolls 58 participants aged 25 or younger. The goal is to see if this drug combination delays tumor growth better than past treatments.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: dabrafenib and trametinib (targeted cancer drugs)
What this could lead to: If successful, this combination could offer a more effective treatment option for children and young adults with this aggressive brain tumor.
What could go wrong: This is a small, early-phase trial with only 58 participants, so results may not apply to everyone. The drugs can cause side effects like fever, rash, and heart issues.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 2

Tests whether the treatment actually works, and watches for side effects, in a larger group.

Participants

About 58 people

The number the study aims to enrol. It can still change while the study runs.

Started

Feb 2020

Expected to finish

Sep 2027

An estimate. End dates often move.

Lead sponsor

A government research agency

The lead sponsor is the US National Institutes of Health.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

3 to 25 years

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * PRE-ENROLLMENT ELIGIBILITY SCREENING: Patients must be =\< 25 years of age at the time of enrollment on APEC14B1 Part A CNS/HGG pre-enrollment eligibility screening. * Note: This required age range applies to the pre-enrollment eligibility screening for all HGG patients. Individual treatment protocols may have different age criteria. * PRE-ENROLLMENT ELIGIBILITY SCREENING: Patient is suspected of having localized newly-diagnosed HGG, excluding metastatic disease. * PRE-ENROLLMENT ELIGIBILITY SCREENING: Patient and/or their parents or legal guardians have signed informed consent for eligibility screening on APEC14B1 Part A. * PRE-ENROLLMENT ELIGIBILITY SCREENING: The specimens obtained at the time of diagnostic biopsy or surgery must be submitted through APEC14B1 as soon as possible (ASAP), preferably within 5 calendar days of the procedure. * Please note: See the APEC14B1 Manual of Procedures for a full list of detailed instructions for submitting required materials and for shipping details. * Patients must be \>= 3 years and =\< 25 years of age at the time of enrollment. * Patients must have eligibility confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1: * Newly diagnosed high-grade glioma with BRAF\^V600-mutation * Results for H3 K27M by immunohistochemistry (IHC) or sequencing * Histologically confirmed high-grade glioma (World Health Organization \[WHO\] grade III or IV) including but not limited to: anaplastic astrocytoma (AA), anaplastic pleomorphic xanthoastrocytoma (aPXA), anaplastic gangliogliomas (aGG), glioblastoma (GB), and high-grade astrocytoma, not otherwise specified (NOS). * Patients must have had histologic verification of a high-grade glioma diagnosis. CSF cytology by lumbar puncture must be done if clinically indicated and determined to be safe prior to study enrollment. If cytology proves positive, the patient would be considered to have metastatic disease and would, therefore, be ineligible. * A pre- and post-operative brain MRI with and without contrast and a baseline spine MRI with contrast must be obtained prior to enrollment. The requirement for a post-operative MRI is waived for patients who undergo biopsy only. If the spine MRI is positive, the patient would be considered to have metastatic disease and would be ineligible. * 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. * Peripheral absolute neutrophil count (ANC) \>= 1000/uL (within 7 days prior to enrollment). * Platelet count \>= 100,000/uL (transfusion independent) (within 7 days prior to enrollment). * Hemoglobin \>= 8.0 g/dL (may receive red blood cell \[RBC\] transfusions) (within 7 days prior to enrollment). * Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 (within 7 days prior to enrollment) or * A serum creatinine based on age/sex as follows (within 7 days prior to enrollment): * Age 3 to \< 6 years (Male 0.8 mg/dL, Female 0.8 mg/dL) * Age 6 to \< 10 years (Male 1 mg/dL, Female 1 mg/dL) * Age 10 to \< 13 years (Male 1.2 mg/dL, Female 1.2 mg/dL) * Age 13 to \< 16 years (Male 1.5 mg/dL, Female 1.4 mg/dL) * Age \>= 16 years (Male 1.7 mg/dL, Female 1.4 mg/dL) * The threshold creatinine values in this table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Centers for Disease Control and Prevention (CDC). * Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment), and * Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L. * Patients with a seizure disorder may be enrolled if their seizures are well controlled while on non-enzyme inducing anticonvulsants permitted on this study. * Patients must be enrolled and protocol therapy must be projected to begin no later than 31 days after definitive surgery (day 0). If a biopsy only was performed, the biopsy date will be considered the date of definitive surgery. For patients who have a biopsy or incomplete resection at diagnosis followed by additional surgery, the date of the last resection will be considered the date of definitive surgery. * All patients and/or their parents or legal guardians must sign a written informed consent. Exclusion Criteria: * Patients with intrinsic brainstem or primary spinal cord tumors will be excluded. * Patients with metastatic disease (defined as neuraxis dissemination either by imaging or by cytology) will be excluded. * Patients must not have received any prior tumor-directed therapy including chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant for the treatment of HGG other than surgical intervention and/or corticosteroids. * Previous treatment with dabrafenib or another RAF inhibitor, trametinib or another MEK inhibitor, or an ERK inhibitor. * Patients with a history of a malignancy with confirmed activating RAS mutation. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to dabrafenib, trametinib, and their excipients. * Uncontrolled medical conditions (e.g., diabetes mellitus, hypertension, liver disease, or uncontrolled infection), psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol. * Presence of active gastrointestinal (GI) disease or other condition (e.g., small bowel or large bowel resection) that will interfere significantly with the absorption of drugs. * History of hepatitis B virus, or hepatitis C virus infection (patients with laboratory evidence of cleared hepatitis B virus and/or hepatitis C virus may be enrolled). * History or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the study such as uncontrolled or significant cardiac disease, including any of the following: * Recent myocardial infarction (within the last 6 months); * Uncontrolled congestive heart failure; * Unstable angina (within last 6 months); * Clinically significant (symptomatic) or known, uncontrolled cardiac arrhythmias (e.g., sustained ventricular tachycardia, and clinically significant second or third degree atrioventricular \[AV\] block without a pacemaker) except sinus arrhythmia within the past 24 weeks prior to the first dose of study treatment; * Coronary angioplasty or stenting (within last 6 months); * Intra-cardiac defibrillators; * Abnormal cardiac valve morphology (\>= grade 2) documented by echocardiogram. * Patients with a history or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR), or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension). * Patients with presence of interstitial lung disease or pneumonitis. * Female patients who are pregnant are ineligible since there is yet no available information regarding human fetal or teratogenic toxicities. * Lactating females are not eligible unless they have agreed not to breastfeed their infants for the duration of the study and for 4 months following discontinuation of study therapy. * Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained. * Sexually active patients of reproductive potential (male or female) are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation and for 4 months following discontinuation of study therapy. Male patients (including those who have had a vasectomy) taking dabrafenib and trametinib combination therapy must use a condom during intercourse while on study and for 16 weeks after stopping treatment, and should not father a child during these periods. Women of childbearing potential should use effective non-hormonal contraception during therapy and for 4 weeks following discontinuation of dabrafenib and at least 4 months following the last dose of trametinib in patients taking combination therapy. Women should be advised that dabrafenib may decrease the efficacy of hormonal contraceptives and an alternate method of contraception, such as barrier methods, should be used.

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Conditions

The condition(s) this trial relates to.

anaplastic astrocytoma anaplastic ganglioglioma anaplastic pleomorphic xanthoastrocytoma astrocytoma (excluding glioblastoma) glioblastoma glioma grade III glioma high grade astrocytic tumor malignant glioma

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Anaplastic astrocytoma Anaplastic astrocytoma, not otherwise specified Anaplastic ganglioglioma Anaplastic pleomorphic xanthoastrocytoma Glioblastoma Malignant glioma Who grade 3 glioma Who grade 4 glioma

Contacts and locations

Locations

AdventHealth Orlando

Orlando, Florida, 32803, United States
Albany Medical Center

Albany, New York, 12208, United States
Alfred I duPont Hospital for Children

Wilmington, Delaware, 19803, United States
Arkansas Children's Hospital

Little Rock, Arkansas, 72202-3591, United States
Arnold Palmer Hospital for Children

Orlando, Florida, 32806, United States
Ascension Saint Vincent Indianapolis Hospital

Indianapolis, Indiana, 46260, United States
BI-LO Charities Children's Cancer Center

Greenville, South Carolina, 29605, United States
Banner Children's at Desert

Mesa, Arizona, 85202, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States
Bronson Methodist Hospital

Kalamazoo, Michigan, 49007, United States
C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States
Cardinal Glennon Children's Medical Center

St Louis, Missouri, 63104, United States
Carilion Children's

Roanoke, Virginia, 24014, United States
Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, 28203, United States
Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, 30329, United States
Children's Hospital Colorado

Aurora, Colorado, 80045, United States
Children's Hospital Los Angeles

Los Angeles, California, 90027, United States
Children's Hospital Medical Center of Akron

Akron, Ohio, 44308, United States
Children's Hospital New Orleans

New Orleans, Louisiana, 70118, United States
Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, 68114, United States
Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States
Children's Hospital of Michigan

Detroit, Michigan, 48201, United States
Children's Hospital of Orange County

Orange, California, 92868, United States
Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States
Children's Hospital of San Antonio

San Antonio, Texas, 78207, United States
Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507, United States
Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, 55404, United States
Children's Mercy Hospitals and Clinics

Kansas City, Missouri, 64108, United States
Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States
Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States
Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States
Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States
Cook Children's Medical Center

Fort Worth, Texas, 76104, United States
Corewell Health Children's

Royal Oak, Michigan, 48073, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States
Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States
Dayton Children's Hospital

Dayton, Ohio, 45404, United States
Dell Children's Medical Center of Central Texas

Austin, Texas, 78723, United States
East Carolina University

Greenville, North Carolina, 27834, United States
East Tennessee Childrens Hospital

Knoxville, Tennessee, 37916, United States
Eastern Maine Medical Center

Bangor, Maine, 04401, United States
Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, 33908, United States
HIMA San Pablo Oncologic Hospital

Caguas, 00726, Puerto Rico
Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States
Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States
Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States
Kaiser Permanente Downey Medical Center

Downey, California, 90242, United States
Kaiser Permanente-Oakland

Oakland, California, 94611, United States
Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, 96826, United States
Legacy Emanuel Children's Hospital

Portland, Oregon, 97227, United States
Lehigh Valley Hospital-Cedar Crest

Allentown, Pennsylvania, 18103, United States
Loma Linda University Medical Center

Loma Linda, California, 92354, United States
Lucile Packard Children's Hospital Stanford University

Palo Alto, California, 94304, United States
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Torrance, California, 90502, United States
Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States
Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, 54449, United States
Mary Bridge Children's Hospital and Health Center

Tacoma, Washington, 98405, United States
Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States
Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States
MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States
Medical City Dallas Hospital

Dallas, Texas, 75230, United States
Medical University of South Carolina

Charleston, South Carolina, 29425, United States
Memorial Health University Medical Center

Savannah, Georgia, 31404, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida, 33021, United States
Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States
Mercy Hospital Saint Louis

St Louis, Missouri, 63141, United States
Miller Children's and Women's Hospital Long Beach

Long Beach, California, 90806, United States
Mission Hospital

Asheville, North Carolina, 28801, United States
Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467, United States
Morristown Medical Center

Morristown, New Jersey, 07960, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States
Nationwide Children's Hospital

Columbus, Ohio, 43205, United States
Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, 32207, United States
Nemours Children's Hospital

Orlando, Florida, 32827, United States
Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States
Nicklaus Children's Hospital

Miami, Florida, 33155, United States
Norton Children's Hospital

Louisville, Kentucky, 40202, United States
Novant Health Presbyterian Medical Center

Charlotte, North Carolina, 28204, United States
OSF Children's Hospital of Illinois

Peoria, Illinois, 61637, United States
Ochsner Medical Center Jefferson

New Orleans, Louisiana, 70121, United States
Oregon Health and Science University

Portland, Oregon, 97239, United States
Penn State Children's Hospital

Hershey, Pennsylvania, 17033, United States
Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States
Primary Children's Hospital

Salt Lake City, Utah, 84113, United States
Prisma Health Richland Hospital

Columbia, South Carolina, 29203, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital

Toledo, Ohio, 43606, United States
Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, 99204, United States
Rainbow Babies and Childrens Hospital

Cleveland, Ohio, 44106, United States
Rhode Island Hospital

Providence, Rhode Island, 02903, United States
Riley Hospital for Children

Indianapolis, Indiana, 46202, United States
Roswell Park Cancer Institute

Buffalo, New York, 14263, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

New Brunswick, New Jersey, 08903, United States
Sacred Heart Hospital

Pensacola, Florida, 32504, United States
Saint Joseph's Hospital/Children's Hospital-Tampa

Tampa, Florida, 33607, United States
Saint Joseph's Regional Medical Center

Paterson, New Jersey, 07503, United States
Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States
Saint Luke's Cancer Institute - Boise

Boise, Idaho, 83712, United States
Saint Mary's Medical Center

West Palm Beach, Florida, 33407, United States
Sanford Broadway Medical Center

Fargo, North Dakota, 58122, United States
Scott and White Memorial Hospital

Temple, Texas, 76508, United States
Seattle Children's Hospital

Seattle, Washington, 98105, United States
State University of New York Upstate Medical University

Syracuse, New York, 13210, United States
Tampa General Hospital

Tampa, Florida, 33606, United States
The Children's Hospital at TriStar Centennial

Nashville, Tennessee, 37203, United States
The Steven and Alexandra Cohen Children's Medical Center of New York

New Hyde Park, New York, 11040, United States
UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States
UF Health Cancer Institute - Gainesville

Gainesville, Florida, 32610, United States
UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States
UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States
University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States
University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States
University of Illinois

Chicago, Illinois, 60612, United States
University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States
University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States
University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States
University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States
University of New Mexico Cancer Center

Albuquerque, New Mexico, 87106, United States
University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States
University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States
University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States
University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States
VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298, United States
Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States
Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States
Walter Reed National Military Medical Center

Bethesda, Maryland, 20889-5600, United States
Washington University School of Medicine

St Louis, Missouri, 63110, United States
Yale University

New Haven, Connecticut, 06520, United States

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