New drug cocktail aims to outsmart childhood brain tumors
NCT ID NCT06712875
First seen Jul 10, 2026 · Last updated Jul 10, 2026
Summary
This pilot study tests whether combining targeted therapy (MAPK inhibitors like trametinib and dabrafenib) with an immunotherapy drug (nivolumab) can safely and effectively treat children with BRAF-altered gliomas, a type of brain tumor. The study includes children with low-grade or high-grade gliomas that have returned or are hard to treat. The goal is to see if this combination can improve tumor control and reduce the chance of tumor regrowth after treatment.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- Trametinib, dabrafenib, and nivolumab
- What this could lead to
- If successful, this combination could offer a new treatment option for children with BRAF-altered gliomas that are hard to treat, potentially improving tumor control and survival.
- What could go wrong
- This is an early-phase pilot study with a small number of participants. The combination may cause significant side effects, and it is unknown if it will work better than current therapies.
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
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Phase 1/2
Runs two stages together: safety and dose first, then whether the treatment works.
- Participants
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About 27 people
The number the study aims to enrol. It can still change while the study runs.
- Started
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Apr 2025
- Expected to finish
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Jun 2029
An estimate. End dates often move.
- Lead sponsor
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Other sponsor
The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
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1 year to 26 years
- Sex
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Anyone
- Healthy volunteers
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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 Hide 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: Cohort A Only: * Patients with histologically confirmed diagnosis of pediatric high- or low-grade glioma harboring a KIAA1549-BRAF fusion: Low-grade glioma that is recurrent or progressive OR High-grade glioma that is newly diagnosed or recurrent OR * Patients with NF1-associated gliomas or NF1-altered glioma: Low-grade glioma that is recurrent or progressive OR High-grade glioma that is newly diagnosed or recurrent OR Transforming glioma that is newly diagnosed or recurrent Cohort B Only: * Patients with histologically confirmed diagnosis of pediatric low-grade glioma harboring a BRAFV600 mutation that is recurrent or progressive OR * Patients with histologically confirmed diagnosis of non-brainstem pediatric high-grade glioma harboring BRAFV600 mutation that is newly diagnosed, recurrent, or progressive All Cohorts: * Patients must be ≥1 and ≤26 years of age at the time of enrollment. * Patients must have a performance status of Karnofsky \>50% for patients \>16 years old and Lansky \>50% for patients \<16 years old. * Patients must have adequate organ and bone marrow function * The effects of dabrafenib, trametinib, and nivolumab on the developing human fetus are unknown. For this reason, patients of childbearing potential (POCBP) and patients with sperm-producing reproductive capacity (PWSPRC) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from time of informed consent for the duration of study participation and for 30 days following completion of therapy. POCBP must have a negative pregnancy test. * Patients with neurological deficits that are stable for a minimum of 1 week prior to enrollment are eligible. Note: A baseline detailed neurological exam should clearly document the neurological status of the patient at the time of enrollment on the study. \- Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment. Total dexamethasone dose at time of enrollment must be less than or equal to 2 mg/day total or 0.5 mg/kg/day, whichever is smaller. LGG Only * Patients must have received a prior BRAF inhibitor (first or second generation), MEK inhibitor, or a combination. The response to this therapy must be known and information provided at study enrollment. * Patients must have recovered from acute treatment-related toxicities (defined as \<Grade 1, excludes alopecia) prior to entering this study. HGG Only * Patients must have received prior radiotherapy \>12 weeks prior to enrollment. * Patients must have recovered from acute treatment-related toxicities (defined as \<Grade 1, excludes alopecia) prior to entering this study. * NF1 patients with transforming gliomas and high-grade gliomas are eligible regardless of prior systemic therapy. * Patients who have received prior radiation therapy must have experienced progression post-radiation OR have measurable disease defined as residual tumor \>1cm in at least one dimension Exclusion Criteria: * Patients with disseminated disease. * Patients who have had prior radiation therapy \<12 weeks prior to registration. * Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) (with the exception of alopecia). * Patients who receiving any other investigational agents. Note: There will be a 21-day washout period for all chemotherapeutic agents, a washout period of two half-lives for any targeted agents (e.g., MAPK inhibitors), and/or a washout period of 4 weeks for any antibody therapies (e.g., bevacizumab). * Patients who have a history of allergic reactions attributed to compounds of similar chemical or biological composition to dabrafenib, trametinib, or nivolumab. * Patients who have received MAPK inhibitor and checkpoint blockade combination therapy. Note: Patients may have received MAPK inhibitor monotherapy or checkpoint blockade monotherapy. * Patients who previously discontinued BRAF inhibitor (type 1 inhibitor or dimer inhibitor, such as, DAY101), MEK inhibitor, or the combination because of grade 3 or higher toxicity or clinically significant grade 2 toxicity requiring discontinuation of therapy are not eligible. * Patients with the following: * Known autoimmune disorders * Immune disorders * Immunodeficiencies * Patients with Crohn's disease, ulcerative colitis, or other inflammatory bowel disease. * Patients with active pancreatitis or history of pancreatitis within the last 3 months. * Patients with active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis requiring treatment with systemic steroids. * Patients who have a known active Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C infection are ineligible. Patient must have documented evidence of negative tests for the presence of HIV, Hepatitis B surface antigen, and Hepatitis C (anti-HCV antibody OR Hep C RNA-qualitative). * Patients who have received a major surgical procedure ≤ 28 days of beginning study treatment, or minor surgical procedures (including VP shunt placement or stereotactic biopsy of the tumor) ≤ 7 days are not eligible. * Patients who are taking herbal preparations. These medications include but are not limited to St. John's wort, kava, ephedra (ma hung), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng. Cannabis products of any type are not allowed throughout the study. Patients should stop using these herbal medications or cannabis products 7 days prior to enrollment. * Patients who are pregnant. Patients of childbearing potential must have a negative serum or urine pregnancy test. (If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.) * Patients who are lactating (unless they have agreed to not breastfeed). Breastfeeding patients are excluded from this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies. * Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic, or other organ dysfunction), that in the opinion of the investigator would compromise the patient's ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results. * Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen for this trial. * Patients with bulky tumor on imaging are ineligible. Bulky tumor is defined as: * Tumor with any evidence of clinically significant uncal herniation or midline shift * Tumor with diameter of \>5cm in one dimension on T2/FLAIR except for those patients with newly diagnosed HGG treated following irradiation without signs of tumor progression. For the latter group, a maximum diameter of contrast enhancing solid or necrotic tumor and of T2/FLAIR abnormality will be 5 cm and 8 cm, respectively. * Tumor that in the opinion of the site investigator, shows significant mass effect * Metastatic disease: Patients with ≤ 5 separate foci of metastatic disease not causing mass effect on adjacent parenchyma and each measuring less than 0.5 cm in maximum diameter will be eligible for this arm of the study. Patients with leptomeningeal disease are eligible. * Multi-focal disease (patients with multi-focal parenchymal disease will be eligible if the sum of the product of the maximum perpendicular diameters of all measurable non-contiguous lesions is less than 16 cm2 based on the T2/FLAIR abnormality).
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Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
How to take part
Only the study team decides who joins. These are the ways to reach them.
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The places running it
3 sites. The list below names each one and where it is.
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The official record
ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.
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A doctor treating you
A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.
Contacts and locations
Locations
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Ann & Robert H. Lurie Children's Hospital of Chicago
RECRUITINGChicago, Illinois, 60611, United States
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Children's National Hospital
NOT_YET_RECRUITINGWashington D.C., District of Columbia, 20010, United States
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Memorial Sloan Kettering Cancer Center
NOT_YET_RECRUITINGNew York, New York, 10065, United States
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