A Phase 2 Study of Veliparib (ABT-888, IND # 139199) and Local Irradiation, Followed by Maintenance Veliparib and Temozolomide, in Patients with Newly Diagnosed High-Grade Glioma (HGG) without H3 K27M or BRAFV600 Mutations

A Phase 2 Study of Veliparib (ABT-888, IND # 139199) and Local Irradiation, Followed by Maintenance Veliparib and Temozolomide, in Patients with Newly Diagnosed High-Grade Glioma (HGG) without H3 K27M or BRAFV600 Mutations Recent landmark molecular genetic landscape studies of pediatric high-grade glioma (HGG) have established distinct, molecularly defined biological subgroups with striking differences in outcome. However, in the past accrual to Children’s Oncology Group (COG) HGG studies was based purely on histopathological diagnosis, leading to considerable heterogeneity in regard to molecular features and tumor biology. As a result, these cohorts included very high-risk tumors with a dismal outcome, such as K27M mutant HGG, as well as favorable risk tumors, such as IDH mutant HGG. In this study, we will select a subset of pediatric HGG based on molecular features at study entry that may be most likely to benefit from the experimental therapy. Outcome of this patient cohort will be compared to historical controls with closely matching molecular features. Eligible patients will be treated with an experimental regimen that includes the Poly (ADP-ribose) polymerase (PARP) inhibitor, veliparib, during radiation therapy, followed by veliparib in combination with temozolomide. Veliparib has a biological rationale for use in pediatric HGG, and synergistic mechanisms of action in combination with either radiation therapy or temozolomide. This study will test whether the proposed combination therapy will improve event-free survival in patients with newly-diagnosed HGG who are wild-type for H3 K27M, IDH, and BRAF (Stratum 1). The study will also include patients with IDH mutant glioma on a separate study arm (Stratum 2). Outcome for all patients will be compared to clinically and molecularly-matched historical control cohorts.