Every year, about 2,200 US children aged less than 20 years are diagnosed with a malignant brain tumor. Brain stem gliomas are the tumors originating in the stem of the brain and account for 10% to 15% percent of pediatric brain tumors. Most brain stem gliomas occur in the pons (hence "pontine gliomas") and are highly aggressive and infiltrative. The peak incidence is between ages 5 and 10. Diffuse intrinsic pontine glioma (DIPG) composes 80% of brain stem tumors and has a median survival of approximately 12 months. Fewer than 10% of patients survive for longer than 2 years after diagnosis. The diagnosis of these tumors is currently based on imaging characteristics alone, since biopsies at these critical locations are risky. The current standard of care for patients with DIPG is focal radiotherapy, surgery, and chemotherapy to reduce tumor mass. Unfortunately, the cancer usually recurs after 6 to 9 months and progress rapidly, especially in treatment with radiation therapy. Thus, currently there is no effective way to treat this disease.
A recent high-resolution single nucleotide polymorphism (SNP)-based DNA microarray analysis of a series of DIPGs found that 50% of DIPGs show amplification of either PDGFA or PDGFRA, and all show overexpression of PDGFRα and phosphor-mTOR, suggesting that activation of this pathway may be an important mechanism in these tumors. A novel treatment for this subset of DIPGs with amplification of PDGFRA is definitely needed.
Phase I Trial in Pediatric Patients with High Grade Glioma (including DIPG)
AROG Pharmaceuticals is conducting a Phase I Trial to investigate the safety of crenolanib in pediatric high grade glioma patients both as a single agent and in combination with radiation.
Phase I/II trial in pediatric high grade gliomas
Key inclusion criteria
Site: St. Jude Children’s Research Hospital