Funded Projects

DNA Analysis of Paediatric Low-Grade Astrocytomas Identifies Tumour-Specific Signature in Pilocytic Astrocytomas

This detailed study, conducted by Dr. Denise Sheer from Queen Mary/University of London and others, focuses on DNA methylation and gene expression to improve researchers’ understanding of the biology of pilocytic and diffuse astrocytomas. Pilocytic Astrocytomas were found to have a distinctive signature at 315 CpG sites, of which 312 were hypomethylated and 3 were hypermethylated.

• Principal Investigator Dr. Denise Sheer, Queen Mary/University of London

Dissecting Cellular Interactions in Pediatric Low-grade Gliomas

The growth of pediatric low-grade gliomas (pLGGs), which occur in the context of a developing brain but then stall during adulthood, is likely to depend upon interactions between cancer cells and cells within their micro-environment.

• Award $204,686 over 1 year (2022-2023)
• Principal Investigators Dr. Mimi Bandopadhayay, Dana Farber Cancer Institute
• Funding Partners Jack’s Drive55

DFCI Clinical Research Assistant – Tissue Harvesting

A three-year funding grant was approved to hire a dedicated Clinical Research Assistant with dedicated responsibilities for increasing the number of brain tumor tissue samples available for research purposes. The main goals of this position is to increase the number of pediatric patients who consent to tissue banking, facilitate the banking of specimens at the time of surgery, and help ensure that all pathology review required as part of clinical trials is completed.

Development of Permanent Juvenile Pilocytic Astrocytoma Cell Lines for Preclinical Trails

This study at University of Texas M.D. Anderson Cancer Center, led by principal investigator Dr. Kwong-Kwok Wong, will investigate different methods to immortalize JPA primary cells which have limited growth potential. Cell culture method will involve the expressing of telomerase gene into JPA primary cells with limited growth potential.

• Principal Investigator Dr. Kwong-Kwok Wong, University of Texas M.D. Anderson Cancer Center

David Andrysiak Clinical Research Assistant

The David Andrysiak Clinical Research Assistant Position provides essential support to Dana Farber Cancer Institute’s local and international PLGA research program activities as well as other brain tumor patients.

• Award: $212,000 over 3 years (2022 – 2025)
• Principal Investigators Dr. Keith Ligon, Chief Neuropathologist, Dana Farber Cancer Institute

Controlling Pilocytic Astrocytoma Growth: Effects of Location, Age and Telomerase

This study, led by principal investigator Dr. Jeffrey Leonard at Washington University, is evaluating three growth characteristics of JPA that might offer clues for research. First, JPA is primarily a disease of childhood. Second, JPAs behave differently when they occur in different parts of the brain.

• Principal Investigators Dr. Jeffrey Leonard, Washington University

Clinical Research Assistant for Tissue Harvesting Initiative

This position works within the Pediatric Neuro-Oncology Program at the Dana-Farber/Children’s Hospital Cancer Center as well as the Center for Neuro-Oncology at Dana-Farber Cancer Center, the Neurosurgery and Neuropathology Departments at Brigham and Women’s Hospital and Children’s Hospital Boston to facilitate tissue banking at these hospitals.

PNOC021 Phase I Trial Evaluating the Combination of Trametinib and Everolimus in Pediatric and Young Adult Patients with Recurrent Gliomas

Given the available preclinical data suggesting synergy with the combination of MEK and mTOR inhibition as well as demonstrated safety and efficacy of trametinib and everolimus in children with LGGs, this trial proposes to evaluate the combination of trametinib and everolimus in children with recurrent or refractory LGGs.

• Award $300,000 over 2 years (2020 – 2022)
• Principal Investigators Dr. Lindsay Kilburn, Children’s National Medical Center, Dr. Angela Waanders, Lurie Children’s Hospital of Chicago, Dr. Mohamed AbdelBaki, Nationwide Children’s Hospital

Phase I/II study of MEK162 for children with progressive or recurrent low-grade gliomas and other central nervous system tumors

Phase I of this trial was rolled out in 2016 with support from PLGA Fund and had a target validation component to determine the ability of MEK162 to penetrate into the tumor as well as assess the ability of MEK162 to affect its target. A short course pharmacokinetics and pharmacodynamic evaluation on these patients for correlation was performed to evaluate the following criteria: To quantify concentration of investigational compound in tumor tissue after treatment with MEK162 for 7-21 days and correlate with PK assessment in blood; to assess RAS-RAF-MEK-ERK pathway inhibition, as measured by ERK phosphorylation, in LGG after treatment with MEK162 for 7-21 days. Blood pharmacodynamic assessment will also be performed and correlated with tumor results. MEK162 demonstrated a positive response; with such promising initial results, researchers expanded the enrollment by 33% (from 75 patients to 100) and allowed current patients to remain on the trial for an additional year.

• Award $250,000 over 2 years (2020 – 2022)
• Principal Investigators Dr. Nathan Robison, Pediatric Neuro-Oncology Attending, Children’s Hospital Los Angeles, Dr. Mariella Gruber, Department of Pediatric Neuro-Oncology, Dana-Farber Cancer Institute, Dr. Karen Wright, Pediatric Neuro-Oncologist, Dana-Farber Cancer Institute
• Funding Partners Taylor Matthews Foundation, WhyNotMe? Foundation, Making Headway

Prospective Assessment of Predictive/prognostic molecular biomarkers in the SIOP-LGG 201X adaptive phase III clinical trial

The principle aim of the trial is to identify the optimum treatment regimen with respect to efficacy, improvement of visual and neurological function, reduction of neurotoxicity as well as treatment duration using a randomized comparison of vinblastine (VBL) versus vincristine (VCR) in a carboplatin-based chemotherapy regimen, also randomizing 18 versus 12 months treatment duration. An additional novel point of the planned trial is the adaptive design and interim analyses (from year 3 onwards), which will allow for the timely investigation of novel targeted agents, once a chemotherapy standard of care ‘winner’ has been established (VCR vs VBL, 12 vs 18 months).

• Award $428,000 over 2 years (2019 – 2021)
• Principal Investigators Dr. David Jones and Dr. Stefan Pfister, Heidelberg German Cancer Institute