Dabrafenib Combined With Trametinib After Radiation Therapy in Treating Patients With Newly-Diagnosed High-Grade Glioma

Running, not enrolling · Phase 2

Conditions studied: Anaplastic Astrocytoma, Anaplastic Astrocytoma, Not Otherwise Specified, Anaplastic Ganglioglioma, Anaplastic Pleomorphic Xanthoastrocytoma, Glioblastoma, Malignant Glioma, WHO Grade 3 Glioma, WHO Grade 4 Glioma

In brief

This phase II trial studies how well the combination of dabrafenib and trametinib works after radiation therapy in children and young adults with high grade glioma who have a genetic change called BRAF V600 mutation. Radiation therapy uses high energy rays to kill tumor cells and reduce the size of tumors. Dabrafenib and trametinib may stop the growth of tumor cells by blocking BRAF and MEK, respectively, which are enzymes that tumor cells need for their growth. Giving dabrafenib with trametinib after radiation therapy may work better than treatments used in the past in patients with newly-diagnosed BRAF V600-mutant high-grade glioma.

Key facts

Study ID

NCT03919071

Run by

National Cancer Institute (NCI)

People needed

58

Starts

2020-02-20

Expected to finish

2027-09-30

Last updated by the study team

2026-07-10

Who can join

Age: 3 and older, up to 25. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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).

You may not qualify if…

• 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.

Where it is running

• Banner Children's at Desert — Mesa, Arizona, United States
• Phoenix Childrens Hospital — Phoenix, Arizona, United States
• Arkansas Children's Hospital — Little Rock, Arkansas, United States
• Kaiser Permanente Downey Medical Center — Downey, California, United States
• Loma Linda University Medical Center — Loma Linda, California, United States
• Miller Children's and Women's Hospital Long Beach — Long Beach, California, United States
• Children's Hospital Los Angeles — Los Angeles, California, United States
• Cedars-Sinai Medical Center — Los Angeles, California, United States
• Kaiser Permanente-Oakland — Oakland, California, United States
• Children's Hospital of Orange County — Orange, California, United States
• Lucile Packard Children's Hospital Stanford University — Palo Alto, California, United States
• University of California Davis Comprehensive Cancer Center — Sacramento, California, United States
• UCSF Medical Center-Mission Bay — San Francisco, California, United States
• Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center — Torrance, California, United States
• Children's Hospital Colorado — Aurora, Colorado, United States
• Connecticut Children's Medical Center — Hartford, Connecticut, United States
• Yale University — New Haven, Connecticut, United States
• Alfred I duPont Hospital for Children — Wilmington, Delaware, United States
• MedStar Georgetown University Hospital — Washington D.C., District of Columbia, United States
• Children's National Medical Center — Washington D.C., District of Columbia, United States
• Golisano Children's Hospital of Southwest Florida — Fort Myers, Florida, United States
• UF Health Cancer Institute - Gainesville — Gainesville, Florida, United States
• Memorial Regional Hospital/Joe DiMaggio Children's Hospital — Hollywood, Florida, United States
• Nemours Children's Clinic-Jacksonville — Jacksonville, Florida, United States
• Children's Hospital of Alabama — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.