Actively Recruiting
MAPK Inhibition Combined With Anti-PD1 Therapy for BRAF-altered Pediatric Gliomas
Led by Ann & Robert H Lurie Children's Hospital of Chicago · Updated on 2025-05-29
27
Participants Needed
3
Research Sites
217 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Pediatric gliomas harboring BRAF-alterations, commonly BRAFV600 mutation or KIAA1549-BRAF fusion, are currently treated with either chemotherapy or mitogen activated protein kinase (MAPK) inhibitors, such as, dabrafenib and/or trametinib. Unfortunately, some BRAF-altered gliomas can progress or have rebound growth after discontinuation of therapy. Data from BRAFV600E-mutant melanoma has shown potential synergy between MAPK inhibition and anti-programmed cell death 1 (anti-PD1) checkpoint blockade. Anti-PD1 therapy, such as, nivolumab can block the PD1 receptor on T cells, a marker of T cell exhaustion, allowing a continued or more robust anti-tumor immune response. Here, investigators will combine MAPK inhibition with anti-PD1 therapy in recurrent, refractory low grade BRAF-altered glioma and newly diagnosed or recurrent BRAF-altered or NF-altered high grade glioma.
CONDITIONS
Official Title
MAPK Inhibition Combined With Anti-PD1 Therapy for BRAF-altered Pediatric Gliomas
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Patients aged 1 to 26 years at enrollment
- Patients with performance status Karnofsky >50% if older than 16 years or Lansky >50% if younger than 16 years
- Patients with adequate organ and bone marrow function
- Patients with recurrent or progressive low-grade glioma harboring KIAA1549-BRAF fusion or NF1-altered glioma, or newly diagnosed or recurrent high-grade glioma with these alterations (Cohort A)
- Patients with recurrent or progressive low-grade glioma harboring BRAFV600 mutation or newly diagnosed, recurrent, or progressive non-brainstem high-grade glioma with BRAFV600 mutation (Cohort B)
- Patients must have recovered from acute treatment-related toxicities to less than Grade 1 (except alopecia)
- Patients must have stable neurological deficits for at least 1 week before enrollment
- Patients receiving dexamethasone must be on a stable or decreasing dose ≤2 mg/day total or 0.5 mg/kg/day for at least 1 week before enrollment
- Patients with low-grade glioma must have received prior BRAF or MEK inhibitor therapy with known response
- Patients with high-grade glioma must have received prior radiotherapy at least 12 weeks before enrollment
- Patients with NF1 transforming or high-grade gliomas are eligible regardless of prior systemic therapy
- Patients with prior radiation therapy must have disease progression or measurable disease >1 cm in one dimension
- Patients of childbearing potential and sperm-producing patients must agree to use contraception and have negative pregnancy tests if applicable
You will not qualify if you...
- Patients with disseminated disease
- Patients who had radiation therapy less than 12 weeks before registration
- Patients with unresolved toxicities greater than Grade 1 from previous anti-cancer therapy (except alopecia)
- Patients currently receiving other investigational agents without required washout periods
- Patients with allergic reactions to dabrafenib, trametinib, or nivolumab
- Patients previously treated with MAPK inhibitor and checkpoint blockade combination therapy
- Patients who discontinued prior BRAF or MEK inhibitor therapy due to severe toxicity
- Patients with known autoimmune, immune disorders, or immunodeficiencies
- Patients with Crohn's disease, ulcerative colitis, or other inflammatory bowel diseases
- Patients with active or recent pancreatitis within 3 months
- Patients with active or history of interstitial lung disease or pneumonitis requiring steroids
- Patients with active HIV, Hepatitis B, or Hepatitis C infections
- Patients who had major surgery within 28 days or minor surgery within 7 days before treatment
- Patients taking prohibited herbal medications or cannabis products
- Pregnant or lactating patients not agreeing to avoid breastfeeding
- Patients with significant unrelated systemic illnesses that impair study participation
- Patients with prior or concurrent malignancies affecting treatment assessment
- Patients with bulky tumors causing mass effect or uncal herniation or tumors >5 cm in one dimension except specified cases
- Patients with metastatic disease exceeding specified criteria or significant multifocal disease beyond limits
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 3 locations
1
Children's National Hospital
Washington D.C., District of Columbia, United States, 20010
Not Yet Recruiting
2
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60611
Actively Recruiting
3
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Not Yet Recruiting
Research Team
M
Monica Newmark
CONTACT
A
Ashley Plant-Fox, MD
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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