BETHESDA, Md.—Representatives from major stakeholders across the neuro-oncology community gathered at the Brain Tumor Clinical Trial Endpoints Workshop in January to lay bare a critical roadblock that has stymied progress in clinical research into glioblastoma multiform (GBM), the most common primary malignant brain tumor. From this workshop emerged an action plan for the community to follow that is intended to create better pathways for therapy evaluation and accelerate therapy approvals.
The workshop centered on the issue of inconsistent brain tumor imaging practices and data evaluation that has delayed analysis and approval of potential therapies. The action plan established at the workshop addresses areas of focus for the community to follow in order to improve the accuracy and consistency of imaging data, and to facilitate the acceleration of brain tumor therapy approvals using imaging as a criteria.
Central to the action plan is an effort to refine and standardize aspects of the Response Assessment in Neuro-Oncology (RANO) criteria, which is a principal method of gauging the effectiveness of a therapy on a brain tumor. RANO provides a set of guidelines for assessing response to therapies in high-grade gliomas, the most aggressive malignant brain tumors. However, RANO has only been in place for a few years—the workshop attendees agreed with consensus that it remains a work in progress and that the imaging elements of RANO would benefit from additional clarification. The Jumpstarting Brain Tumor Drug Development Coalition, made up of four of the leading brain tumor-focused organizations in the United States—the National Brain Tumor Society, Accelerate Brain Cancer Cure, the Musella Foundation for Brain Tumor Research and Information and the Society for Neuro-Oncology—will aid in the continued refinement of the RANO criteria, and in defining the next version of the criteria’s use and acceptability.
The action plan also aims to establish standards across the brain tumor imaging field that will allow data to be gathered, analyzed, managed and shared in a consistent format. This will enable greater sharing of information across organizations and will simplify the effort to create reproducible data when required for registration trials.
A primary difference between this workshop and other conferences that have taken place in the past was the broad representation from so many stakeholders in the neuro-oncology field. Medical and academic researchers from the major brain tumor clinical research centers met with representatives from more than 10 major biotech and pharmaceutical companies, executives from contract research organizations, representatives from the National Cancer Institute, along with members of medical imaging companies and more than 25 personnel from the U.S. Food and Drug Administration (FDA).
“The action plan—and the fact that it was given the blessing of the FDA—provides true direction and real momentum for this field to begin moving toward the development of standards that could eventually be used by trial sponsors to conduct valid, single-arm trials with imaging-based endpoints to gain accelerated approval for promising therapies,” says David Arons, senior director of public policy at the National Brain Tumor Society.
The formation of the Jumpstarting Brain Tumor Drug Development Coalition and the organization of this winter’s workshop are part of the National Brain Tumor Society’s Clinical Trial Endpoints Initiative, which began in 2012. A landscape analysis conducted by the society uncovered that a lack of brain tumor clinical trials that used endpoints other than “overall survival” has hindered brain tumor drug development. In fact, the analysis noted a “serious” lack of effective brain tumor drugs on the market and in development relative to other forms of cancer.
In response to these findings, in mid-2013, the National Brain Tumor Society and the leadership of the strategic steering committee it had formed—consisting of world-renowned medical researchers, physicians, and biostatisticians from several prestigious institutions—requested a meeting with the FDA to discuss how various stakeholders in brain tumor drug development could work together to increase the volume and speed of approvals for new treatments. Although the FDA agreed to the meeting, it quickly became clear during the ensuing discussion that more of the brain tumor drug development field would need to be convened in order to make significant strides, which led to the idea for the workshop. The FDA again agreed to participate if the National Brain Tumor Society could assemble the neuro-oncology community.
“Most conferences are places for numerous presentations on a number of different subjects with multiple, simultaneous tracks, but not a working group together in one room, focusing on one problem,” says Arons. “Particularly unique, also, was the presence of such a large contingent of FDA staff, as well as representatives from the imaging companies. These groups allowed the conversation to move beyond a typical academic debate into actual problem solving.”
The National Brain Tumor Society is the largest nonprofit dedicated to the brain tumor community in the United States, and is the result of the merging of the National Brain Tumor Foundation and the Brain Tumor Society in 2008. The organization provides catalytic funding, facilitates research collaborations, and advocates for policies that impact those affected by brain tumors, including the roughly 700,000 Americans living with a primary brain tumor.
