Actively Recruiting
Pilot Study Evaluating MAPK Pathway 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
26 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are studying pediatric gliomas that have specific changes in the BRAF gene, such as the BRAFV600 mutation or KIAA1549-BRAF fusion. These gliomas are usually treated with chemotherapy or drugs called MAPK inhibitors like dabrafenib and trametinib. However, some tumors may worsen or grow again after stopping treatment. This study explores combining MAPK inhibitors with an immunotherapy drug called nivolumab, which may help the immune system better fight the tumor in children with these brain cancers. This pilot study evaluates the safety and early effectiveness of combining dabrafenib, trametinib, and nivolumab in children with BRAF-altered or NF-altered gliomas. There are two treatment groups: one receives trametinib plus nivolumab, and the other receives dabrafenib, trametinib, and nivolumab together. Trametinib is given orally once daily, nivolumab is given intravenously every 4 weeks, and dabrafenib is taken orally twice daily. Treatment cycles last 28 days, usually for up to one year or 13 cycles, but patients with high-grade glioma may continue longer if benefiting. Participants will be followed for up to 5 years to assess outcomes. Participants will have regular assessments including monitoring for side effects, tumor response, and survival. Researchers will measure treatment-related adverse events during the first 28 days and evaluate tumor response and progression over one year and up to five years after treatment. Patients must have good performance status and stable neurological symptoms before joining. The study also tracks long-term safety and clinical benefit. This research is led by Ann & Robert H Lurie Children's Hospital of Chicago and aims to understand how well this combination therapy works and its tolerability in pediatric glioma patients.
CONDITIONS
Brief 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
- Histologically confirmed pediatric glioma with either KIAA1549-BRAF fusion, BRAFV600 mutation, or NF1 alteration
- Low-grade glioma that is recurrent or progressive, or high-grade glioma that is newly diagnosed or recurrent
- Karnofsky performance status >50% for patients over 16 years old or Lansky score >50% for patients under 16
- Adequate organ and bone marrow function
- Stable neurological deficits for at least 1 week prior to enrollment
- Patients on dexamethasone must be on a stable or decreasing dose ≤2 mg/day or 0.5 mg/kg/day for at least 1 week
- Low-grade glioma patients must have prior MAPK inhibitor treatment with known response
- High-grade glioma patients must have completed radiotherapy >12 weeks prior and recovered from acute toxicities
- Patients of childbearing potential must use contraception and have a negative pregnancy test
- NF1 patients with transforming or high-grade gliomas are eligible regardless of prior systemic therapy
You will not qualify if you...
- Disseminated disease
- Prior radiation therapy within 12 weeks before registration
- Unresolved adverse events from prior anticancer therapy greater than Grade 1 (except alopecia)
- Receiving other investigational agents without proper washout periods
- History of allergic reaction to dabrafenib, trametinib, or nivolumab
- Previous combination treatment with MAPK inhibitor and checkpoint blockade
- Discontinuation of prior BRAF or MEK inhibitors due to severe toxicity
- Known autoimmune, immune, or immunodeficiency disorders
- Crohn's disease, ulcerative colitis, or other inflammatory bowel disease
- Active or recent pancreatitis within 3 months
- Active or history of interstitial lung disease or pneumonitis requiring steroids
- Known active HIV, Hepatitis B, or Hepatitis C infection
- Major surgery within 28 days or minor surgery within 7 days before study treatment
- Use of certain herbal medications or cannabis products within 7 days prior to enrollment
- Pregnancy or lactation without agreement to not breastfeed
- Significant unrelated systemic illness that may increase risk or interfere with study
- Prior or concurrent malignancy interfering with safety or efficacy assessment
- Bulky tumor with significant mass effect or size exceeding specific limits
- Metastatic or multifocal disease exceeding defined limits
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 1 year or 13 cycles, whichever comes first
Participants receive combination drug therapy with dabrafenib, trametinib, and/or nivolumab depending on their assigned cohort. Treatment cycles repeat every 28 days for up to 1 year or 13 cycles, with possible continuation beyond 13 cycles for high-grade glioma if clinical benefit is observed.
Monthly visits every 4 weeks for drug administration and assessments
Duration - Up to 5 years post treatment
Participants are followed for up to 5 years after treatment to monitor long-term outcomes including progression-free survival and overall survival.
Periodic follow-up visits over 5 years
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
A
Ashley Plant-Fox, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
Similar Trials
Frequently Asked Questions
Have more questions? Get in touch with our team for quick support
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here