National Brain Tumor Society staff and advisors recently met with the U.S. Food and Drug Administration (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 for this disease.
Specifically, the FDA offered their support to:
- Assist the National Brain Tumor Society in bringing clarity to the research and biopharmaceutical communities on imaging and quality of life-related endpoints
- Participate in discussions for developing new strategies and metrics designed to accelerate brain tumor-specific drug development
- Consider drug approvals based on alternative endpoints provided the trials use sufficiently valid data and demonstrate real clinical value to patients – including imaging measures with objective assessments that would require only single-arm trials versus the more costly and complex randomized, double-arm trials.
To meet these goals, the National Brain Tumor Society proposed hosting one or more workshops in early 2014, which the FDA graciously agreed to participate in. The workshops will present the state of the field in brain tumor endpoint measurement and contribute to the development of criteria required for designing valid clinical trials using alternative endpoints. It is our hope these changes will create more incentives for future research and investment in brain tumor treatments and deliver a pipeline of new drugs to the community.
Clinical Trial Endpoints Initiative
The meeting with the FDA was part of the National Brain Tumor Society’s larger “Clinical Trial Endpoints Initiative,” which began in 2012. Led by a strategic Steering Committee of world-renowned medical researchers, physicians, and biostatisticians from prestigious institutions including, Dana Farber Cancer Institute, MD Anderson Cancer Center, John Hopkins Hospital, Mayo Clinic, UCSF, UCLA, and NYU, the Initiative seeks to create change by supporting advancements in the design and evaluation criteria of clinical trials to deliver more value to patients and speed drug development. The Steering Committee’s Chair (Dr. Patrick Wen, MD, Dana Farber Cancer Institute) and Vice Chair (Dr. Terri Armstrong, PhD, MD Anderson Cancer Center) were both present for the meeting with the FDA.
Disappointing results from recent high-profile clinical trials for brain tumor therapeutics, including Cilengitide and Avastin, demonstrate the difficulty researchers and drug manufacturers have in demonstrating clinical benefits for new drugs based on OS alone. Like every medication, potential brain tumor drugs are subject to rigorous clinical trials to ensure safety and effectiveness before receiving FDA approval. For many oncology drugs, these clinical trials primarily aim to improve patient survival over the current standard of care. In more technical terms, the criteria, or “endpoint,” used for evaluation in these clinical trials is Overall Survival (OS), which remains the gold standard of endpoints for oncology drugs. However, achieving clinical trial success on OS alone is costly, time-consuming, and a difficult hurdle for new drugs. Moreover, OS-specific clinical trials seldom provide detailed information on the drug’s effect on quality of life measures, which could also be valuable to the patient community.
“Alternative” endpoints can be selected for evaluation by a clinical trial’s sponsor, including imaging-related endpoints, progression-free survival (PFS), response duration, objective response rate (ORR), time to progression (TTP), as well as quality of life and functional endpoints such as patient reported outcomes (PRO), neurocognitive function, and other symptom-specific measures. However, most of these alternative endpoints have yet to be utilized as valid approval measures in clinical trials for brain tumor drugs.
Ultimately, the development of new drugs, which improve survival, extend lives, and improve a patients’ quality of life is the goal of the Clinical Trial Endpoints Initiative. As such, National Brain Tumor Society will continue to advocate for improvements in OS for pathways of all new brain tumor drugs under development, but what this Initiative hopes to provide is a process that allows potential brain tumor drugs to be approved on alternative endpoints even if OS isn’t demonstrated. With this approach, National Brain Tumor Society can remain true to its mission of finding a cure, and preserve access to other therapies that may have value to some patients, while increasing the availability of new, effective drugs.
Through the National Brain Tumor Society’s engagement with the FDA, the Clinical Trial Endpoints Initiative looks poised to help jump-start drug development, and create positive change for brain tumor patients.