Clinical Trials

The Program’s clinical trials arm has two specific aims: the first is to improve the translation of laboratory findings into clinical trials for children with low-grade gliomas and the second is to increase the Program’s access to biological materials that can be used to support the scientific investigations.  As the majority of pediatric low-grade gliomas carry BRAF mutations that activate the RAS/RAF/MEK pathway, the inhibitors presently under investigation in clinical trials focus on this pathway.

Pediatric Low-Grade Astrocytoma Trials targeting the RAS/RAF/MEK pathway

Trial # Trial Title Test Agent Trial Status
DFCI 09-001 Phase II study of RAD001 in recurrent or refractory low-grade glioma Everolimus Finished
DFCI 09-452 Phase II study of RAD001 in progressive or refractory low-grade glioma in patients with neurofibromatosis type I Everolimus Finished
DFCI 12-429 Phase I/II study of dabrafenib in advanced solid tumors harboring BRAF V600E mutations Dabrafenib Finished
DFCI 15-079 Phase I/II study of trametinib and dabrafenib in plexiform neurofibromas or V600E mutated tumors Dabrafenib


DFCI 15-368 Phase I/II study of MEK162 in recurrent pediatric low-grade glioma and RAS/RAF/ERK pathway activated tumors MEK 162 Ongoing
DFCI 15-369 (PNOC 001) Phase II Study of everolimus for recurrent or progressive low-grade glioma in children Everolimus Ongoing
DFCI 17-532 Phase II open-label global study to evaluate the effect of dabrafenib in combination with trametinib in children and adolescent patients with BRAF V600E mutation positive relapsed or refractory high-grade glioma Dabrafenib


DFCI 17-589 (PNOC 014) Phase I/II study with target validation for pediatric low-grade astrocytoma and other RAS/RAF/MEK/ERK Pathway Activated Tumors TAK 580 Ongoing

More information on the clinical efforts, including trials currently recruiting can be found at and at

There are a number of other pathways that we have recently identified in pediatric low-grade astrocytomas, including the MYBL1 pathway by Keith Ligon, MD, PhD and the MybQKI pathway by Rameen Beroukhim, MD, PhD and Pratiti Bandopadhayay, PhD, MBBS. While those corresponding mutations are less common than the BRAF mutations, early preclinical experiments are already underway to begin testing possible drugs that could be used clinically for tumors with signaling through these alternative pathways. Additionally, fusion genes involving receptor tyrosine kinases (FGFR, NTRK2/3) have been identified in small numbers of low grade gliomas. Inhibitors of these kinases are further candidates in trials.

Tissue Banking

Tissue samples collected from patients undergoing experimental therapies are one of the most valuable resources for development of new treatments of Pediatric Low-Grade Gliomas (PLGG) and understanding patterns of treatment resistance. The tissue bank directed by Keith Ligon, MD, PhD and with AKBTC support provides central pathology coordination for clinical trials with tissue analysis components. These trials include PI initiated as well as Children’s Oncology Group (COG) and national consortium trials. The tissue bank is currently receiving samples for genomic analysis from three active trials (one BRAF inhibitor and one MEK inhibitor, and one chemotherapeutic study). In the past year they completed accrual of Phase 1 in the MEK162 study. These samples were profiled by Oncopanel for more than 500 genes for annotation of BRAF V600E, BRAF fusion, and other LGG driver events to better understand the responses to MEK inhibitors. Phase 2 collection is ongoing and includes collection and processing. In addition they have arranged to collaborate in the analysis of samples on 2 other PLGG clinical therapeutic trials including Pacific Pediatric Neuro-Oncology Consortium (PNOC), COG and other consortia.