PLGA Fund at PBTF

The Pediatric Brain Tumor Foundation and A Kids’ Brain Tumor Cure have joined forces to fund research across the widest breadth of pediatric brain tumors.

The PLGA Fund at PBTF will continue AKBTC's mission of fueling the most promising pediatric low-grade glioma and astrocytoma research (PLGG/PLGA). Eligible projects include basic science, translational and clinical trial initiatives.

THE NEED FOR PLGG/PLGA RESEARCH

More than half of childhood primary central nervous system tumors are gliomas, and, unlike gliomas in adulthood, low-grade gliomas constitute the majority of pediatric gliomas. Pediatric low-grade gliomas arise throughout the nervous system. Despite their slower progression, they are typically not amenable to safe, extensive resections. Current treatments have lasting effects on patients’ quality of life.

Over the past decade, the AKBTC’s research seed funding has enabled scientists to apply and win multi-million-dollar grants from the National Cancer Institute and resulted in five new clinical trials that have helped shape the direction for targeted therapies.

The PLGA Fund at PBTF continues the AKBTC’s work in funding research that will lead to non-toxic, non-invasive treatments and, ultimately, a cure.

We are now accepting PLGA/PLGG research grant proposals at PLGAresearch@curethekids.org. Currently funded projects are detailed below; learn more about previously AKBTC-sponsored research projects here.

The PLGA Fund is made possible by the generosity of fundraisers, donors, and community events across the country. Find a fundraiser or learn more about how you can support the PLGA Fund here.

Phase I/II and Target Validation Study of TAK-580 (MLN2480) for Children with Low-Grade Gliomas and Other RAS/RAF/MEK/ERK Pathway Activated Tumors

Award: $500,000 over 2 years
Principal Investigators: Dr. Karen Wright, Director of Neuro-Oncology, Assistant Professor-Pediatrics, Dana-Farber Cancer Institute, Dr. Daphne Haas-Kogan, Chair-Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women’s Hospital, and Sabine Mueller, Associate Professor of Oncology, University of California, San Francisco
Funding Partner: Taylor Matthews Foundation

The RAS/RAF/MEK/ERK pathway is implicated in a number of adult cancers and NF1-associated tumors. Similarly, the majority of pediatric LGGs possess abnormal signaling through the RAS/RAF/MEK/ERK pathway as do a variety of other CNS tumor types including high grade glioma, pleomorphic xanthoastrocytoma and ganglioma. Complete resection is often not feasible and currently available therapies have limited efficacy, leading to an increased morbidity for these patients. More effective therapies using novel mechanisms of action are needed.

Target Validation: To assess the penetration of TAK-580 into the tumor and assessment of the target as defined by suppression of ERK signaling. This trial has finished Phase I and has shown early evidence of response in patients, thereby satisfying the government and agency requirement regarding lack of toxicity in the pediatric population.  In addition, pharmacokinetic analysis is complete and 18 PNOC sites are poised to open the Phase II trial once funding is secured.

With a generous donor offering a matching grant challenge for up to $125,000, a fundraising campaign is in full swing with intention of fulfilling the funding request as soon as possible to ensure that this treatment is available to a wider patient base as quickly as possible.

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

Award: $250,000 over 1 year
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. Susan Chi, Pediatric Neuro-Oncologist, Dana-Farber Cancer Institute

The target validation component of the study will allow us 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 is also planned.

Primary Endpoint:

• 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 continues to demonstrate a positive response; with such promising initial results, researchers are expanding the enrollment by 33% (from 75 patients to 100) and allowing current patients to remain on the trial for an additional year. 

With a generous donor offering a matching grant challenge for up to $125,000, a fundraising campaign is in full swing with intention of fulfilling the funding request as soon as possible to ensure that this treatment is available to a wider base as quickly as possible.

Clinical Research Assistant - Tissue Harvesting

Award: $100,000 over 2 years
Principal Investigators: Dr. Keith Ligon, Associate Professor Pathology, Harvard Medical School, Associate Pathologist/Neuro-Pathologist, Brigham and Women’s Hospital, Dana-Farber Cancer Institute

This CRA position will work within the clinical research program and support the research team in the overall conduct of clinical trials using Good Clinical Practice under the auspices of the Principal Investigator. The CRA will be responsible for the primary data collection and management of patient clinical information as it pertains to participation in clinical trials. They will ensure timely collection of protocol-related samples including shipment to outside entities as required. The individual will maintain regulatory binders and ensure study compliance with all state, federal, and IRB requirements. The individual may be responsible for IRB protocol submissions (amendments, continuing reviews, and minimal risk protocols). This individual may also screen patients for protocol eligibility, obtain informed consent, and register study participants with the Office of Data Quality (ODQ). They must understand the required basic principles of human research subject protection. The individual must work independently under general supervision.