MAPK Inhibition Combined With Anti-PD1 Therapy for BRAF-altered Pediatric Gliomas

Part of paid clinical trials in Washington D.C., District of Columbia.

Sponsor
Ann & Robert H Lurie Children's Hospital of Chicago
Study ID
NCT06712875
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

  • High Grade Glioma
  • Low Grade Glioma

Eligibility Criteria

Sex
ALL
Age
1 Year - 26 Years
Healthy Volunteers
Not accepted

Interventions

Study Details

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.

Key Dates

Start date
Apr 1, 2025
Status verified
May 2025
Primary completion
Dec 31, 2028
Completion
Jun 30, 2029

Study Design

Enrollment
27 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Trametinib combined with nivolumab (Cohort A)
    Patients with histologically confirmed diagnosis of pediatric high- or low-grade glioma harboring a KIAA1549-BRAF fusion. Patients with NF1-associated gliomas or NF1-altered glioma. Patients in Cohort A will receive trametinib and nivolumab combination therapy. Trametinib will be administered at 0.025 mg/kg/dose orally once daily. Nivolumab will be administered at 6 mg/kg/dose intravenously every 4 weeks. Cycle length will be every 28 days. Treatment will include 1 year or 13 cycles of combination therapy, whichever comes first. For patients with high grade glioma, therapy can be continued beyond the 13 cycles if they are deemed to have clinical benefit from the therapy. Patients will be followed for up to 5 years to evaluate clinical endpoints.
  • Experimental: Dabrafenib + trametinib combined with nivolumab (Cohort B)
    Patients with histologically confirmed diagnosis of pediatric low-grade glioma harboring a BRAFV600 mutation that is recurrent or progressive or non-brainstem pediatric high-grade glioma harbor ng BRAFV600 mutation that is newly diagnosed, recurrent, or progressive. Cohort B will receive trametinib, nivolumab dabrafenib combination therapy. Trametinib will be administered at 0.025 mg/kg/dose orally once daily. Nivolumab will be administered at 6 mg/kg/dose intravenously every 4 weeks. Dabrafenib will be administered at a dose of 5.25 mg/kg/day orally divided into two doses, which shall be taken 12 hours apart. Cycle length will be every 28 days. Treatment will include 1 year or 13 cycles of combination therapy, whichever comes first. For patients with high grade glioma, therapy can be continued beyond the 13 cycles if they are deemed to have clinical benefit from the therapy. Patients will be followed for up to 5 years to evaluate clinical endpoints.

Primary Outcome Measure

Safety based on number of participants with treatment-related adverse events based on scoring from CTCAE v4.0 [ Time Frame: The dose limiting toxicity (DLT) period is 28 days. ]

Central Contacts

Locations (3)

FacilityCityStateZIPSite coordinators
Children's National HospitalWashington D.C.District of Columbia20010
Hameenat Adekoya
[email protected]
202-476-3898
Ann & Robert H. Lurie Children's Hospital of ChicagoChicagoIllinois60611
Monica Newmark
[email protected]
3122274847
Ashley Plant-Fox, MD
[email protected]
312-227-4874
Memorial Sloan Kettering Cancer CenterNew YorkNew York10065
Sameer Farouk
[email protected]

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By research site
Children's National Hospital· Washington D.C., DCAnn & Robert H. Lurie Children's Hospital of Chicago· Chicago, ILMemorial Sloan Kettering Cancer Center· New York, NY

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