Tumor biomarkers (TB) that are validated surrogate endpoints of a drug's therapeutic effect can improve the accuracy and sensitivity of assessing tumor response in phase 2 trials and could also substantially shorten the time line of phase 3 trials if they are predictive of subsequent relapse or survival. Our goal is to identify and validate TB to serve as surrogate endpoints in clinical trials to measure tumor burden and tumor response and to predict relapse. GD2 has many of the characteristics of an ideal biomarker. The overall objective of this proposal is to initiate the validation of GD2, which is expressed on the surface of neuroblastoma and other tumors of neuroectodermal or mesenchymal origin, as a TB for neuroblastoma using existing sample sets. This request is for an exploratory set of serum samples taken at diagnosis from patients with high grade glioma or medulloblastoma to assess the specificity of GD2 as a TB for neuroblastoma and determine whether GD2 is present in the serum of children with CNS tumors.
What are the goals of this project?
THe goal of this project is to quantify serum GD2 concentrations in patients with a variety of common childhood cancers, including brain tumors, and in children without cancer to assess the specificity of GD2 as a tumor biomarker for neuroblastoma or other neuronal tumors.
Our hypothesis is that GD2 will not be quantifiable in the serum of patients with most common types of childhood cancer and children without cancer and that GD2 is a tumor-specific biomarker for neuroblastoma and brain tumors.
What is the impact of this project?
Although our focus is on development of GD2 as a surrogate endpoint, regulatory approval of GD2 as a clinical test7 could provide substantial patient benefit and facilitate the development of GD2 as a research tool by making it widely available. For a TB to be recognized as a valid surrogate endpoint it must be biologically plausible, have prognostic value for a clinical outcome, and predict for treatment effect on the clinical outcome in prospective clinical trials.
This is an exploratory study to screen for the presence and amount of GD2 in the serum of patients with the common forms to childhood cancer, including brain tumors, to evaluate the specificity of GD2 as a biomarker for neuroblastoma as part of the clinical validation process for GD2 as a tumor biomarker for neuroblastoma, and to determine whether it is present in the serum of patients with other types of neuronal tumors.
This pilot study is designed to determine whether GD2 is measurable in the serum of children with common types of cancer other than neuroblastoma, including CNS tumors
The Children's Brain Tumor Network contributed to this project by providing plasma samples.
Frank M. Balis, MD
As CHOP’s Institutional Principal Investigator for the Children’s Oncology Group (COG), I oversee the Cancer Center’s substantial contributions to the national clinical research efforts of the COG. We are striving to be one of the premier pediatric oncology clinical research program in the COG.
Medulloblastomas comprise the vast majority of pediatric embryonal tumors and by definition arise in the posterior fossa, where they constitute approximately 40% of all posterior fossa tumors. Other forms of embryonal tumors each make up 2% or less of all childhood brain tumors.The clinica
High-grade glioma/astrocytoma (WHO grade III/IV)
High-grade Gliomas (HGG) in children nearly always result in a dismal prognosis. Although novel therapeutic approaches are currently in development, preclinical testing has been limited, due to a lack of pediatric specific HGG preclinical models. These models are needed to help test the effective