MAPK Inhibition with Anti-PD1 Therapy for Pediatric Gliomas
This study is looking at new ways to treat pediatric gliomas (brain tumors) that have specific genetic changes called BRAF alterations or NF1 alterations. Currently, these gliomas are treated with chemotherapy or drugs called MAPK inhibitors like dabrafenib and trametinib. However, sometimes these tumors grow back. This study combines MAPK inhibitors (dabrafenib and/or trametinib) with nivolumab, a drug that helps your immune system fight cancer. Researchers want to see if this combination is safe and if it works better than current treatments. You might be eligible if you are between 1 and 26 years old and have a glioma with specific BRAF or NF1 genetic changes. The main goal is to check for side effects within the first 28 days of treatment.
- Study design
- This is an interventional study planning to enroll 27 participants. It is a pilot study evaluating the toxicity and early efficacy of these drug combinations.
- What's involved
- Not specified in the trial record.
- Compensation
- Not stated in the trial record.
- Follow-up
- Safety will be measured based on side effects within the first 28 days of treatment.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT06712875
MAPK Inhibition Combined With Anti-PD1 Therapy for BRAF-altered Pediatric Gliomas
Recruiting
PHASE1Ages 1–26InterventionalTreatmentAnn & Robert H Lurie Children's Hospital of ChicagoInvestigator-initiated
~27 participants
Updated 2026-07-10 on ClinicalTrials.gov
What's tested:Trametinib and NivolumabDabrafenib, trametinib, nivolumab
At a glance
Recruiting sites
1 of 3 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Safety based on number of participants with treatment-related adverse events based on scoring from CTCAE v4.0
Measured over The dose limiting toxicity (DLT) period is 28 days.
Conditions
Where it's being run
3 sites across 3 statesDistrict of Columbia1
Illinois1
New York1
Study leadership
- Ashley Plant-Fox, MD · PRINCIPAL_INVESTIGATOR · Ann & Robert H Lurie Children's Hospital of Chicago
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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
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
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.
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.
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
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.
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).
What this trial measures
- Safety based on number of participants with treatment-related adverse events based on scoring from CTCAE v4.0The dose limiting toxicity (DLT) period is 28 days.
This study will utilize a rolling 6 design and enroll 12 evaluable patients in each cohort (Cohort A and B). Two dose levels will be utilized to assess safety and tolerability. Dose level 1 includes 100% dosing of dabrafenib and/or trametinib and nivolumab. A dose level -1 will be utilized if dose level 1 is not tolerable and will include 100% dosing of nivolumab with 70% dosing of dabrafenib and/or trametinib.