Pediatric Gliomas

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 10.1 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 progresses rapidly, especially in treatment with radiation therapy. Thus, currently there is no effective way to treat this disease.2

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 phospho-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.3


  • ARO-003

    PDGFR Inhibitor Crenolanib in Children/Young Adults With Diffuse Intrinsic Pontine Glioma or Recurrent High-Grade Glioma (NCT01393912)

    This is a Phase I clinical trial evaluating crenolanib (CP-868,596), an inhibitor of Platelet Derived Growth Factor Receptor (PDGFR)-kinase in children and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG) (Stratum A) or in recurrent, progressive or refractory High Grade Glioma (HGG) including DIPG (Stratum B). This study drug targets the most commonly amplified region of genome found in DIPG and pediatric high grade glioma (HGG) which encodes for the PDGF receptor kinase. An oral investigational agent crenolanib will be administered daily during and after local radiation therapy (RT) in Diffuse Intrinsic Pontine Glioma DIPG (Stratum A), or daily for children with recurrent/refractory HGG (Stratum B).

    For more information please see:


Adult Gliomas

Brain tumors (abnormal growth of cancer cells within the brain) comprise 1.44% of all the new cancer cases. In 2010, 22,020 patients are estimated to be diagnosed with cancer of the brain and central nervous system (CNS), and 13,140 patients are estimated to die of the disease.1

Table 1


Primary brain tumors are classified as either gliomas or non-gliomas. Gliomas (tumors of glial cell origin) are the most common tumors of the central nervous system. They account for 32% of all tumors and 80% of malignant tumors, as reported in the Central Brain Tumor Registry of the United States (CBTRUS), 2010.

There is a significant unmet medical need for new and effective drugs for the treatment of both adult and pediatric gliomas. The 1-10 year relative survival rates by histology for 50,240 patients as adapted from CBTRUS 2010 are shown below. The estimated five–and ten–year survival rates collectively for malignant brain tumors are 35% and 32%, respectively.

Role of PDGFR

In primary glioblastomas, PDGFRA gene amplification is observed in approximately 13 – 29% patients1. Furthermore, high level expression of PDGFR? is a characteristic signature in the proneural subtype of glioblastoma1. A recent study showed high frequency of PDGFRA gene amplification and also overexpression of PDGFA and PDGFR?1

Table 1



  • ARO-001

    A Phase II Study of Crenolanib (CP-868,596), a Selective and Potent Inhibitor of PDGFR, for the Treatment of Adult Gliomas (NCT01229644)

    The purpose of this study is to evaluate the antitumor efficacy of crenolanib (CP-868,596) in patients with recurrent high grade glioma and in patients with low grade glioma.

    For more information please see:

1Cancer Facts and Figures, 2014
2Warren, Front Oncol. 2012; 2(205):1-9
3Zarghooni, et al. J Clin Oncol. 2010; 28(8):1337-1344
4Ostrom, et al. Neuro Oncol. 2014; 16(Suppl 4):iv1-iv63