Second Brain Tumor Clinical Trial Endpoints Workshop identified steps needed to include measures of patient signs, symptoms, and function as part of evaluation of therapy benefit
A recent workshop brought together leaders and stakeholders from the neuro-oncology, neurology, and clinical outcomes assessment fields to address the critical issue of incorporating patient-focused endpoints into future brain cancer clinical trials. Known as “clinical outcome assessments (COAs),” measurements of how a brain tumor patient feels and functions have been insufficiently used in brain cancer clinical trials seeking drug approval.
“There is increasing recognition that clinical trials in the neuro-oncology setting that use only radiographic assessments or measures of overall or progression-free survival are inadequate for brain cancer patients,” said Dr. Terri Armstrong of The University of Texas Health Science Center and MD Anderson Cancer Center, and Workshop Co-chair. “We know these patients not only want to live longer, but to live comfortably and function as well as they can, for as long as possible. Unfortunately, too often trials do not adequately include rigorous clinical outcome assessments. Yet, COAs are essential to understanding all of the potential patient benefits of a therapy under evaluation, including reducing symptoms, signs, and improving function.”
Hosted by the Jumpstarting Brain Tumor Drug Development Coalition (Accelerate Brain Cancer Cure, Musella Foundation for Brain Tumor Research & Information, National Brain Tumor Society, and the Society for Neuro-Oncology), more than 100 attendees representing approximately 14 pharmaceutical companies; 19 senior FDA staff; key representatives of the National Cancer Institute; neuro-oncology and neurology research and clinical leaders; nonprofits; and importantly, patients, advocates, and caregivers, participated in the Workshop.
“It is in the best interest of all parties to consider the patients’ perspective when analyzing the risks and benefits of new therapies”, said Dr. Paul Kluetz, Acting Deputy Director of the US Food and Drug Administration’s Office of Hematology and Oncology Products. “We are actively pursuing optimal ways to incorporate patient reported outcomes and functional assessments in clinical trials. In addition to measurement of tumor response and survival, we support the exploration of feasible and reliable methods of evaluating disease-specific symptoms, as well as cognitive and physical function in oncology clinical trials, as we recognize these outcomes are important to brain tumor patients.”
Stakeholder groups worked together through four panel sessions led by Drs. Armstrong, Jaishri Blakeley (Johns Hopkins Hospital), Mark Gilbert (MD Anderson Cancer Center) and Patrick Wen (Dana-Farber Cancer Institute). Participants focused on three key areas that needed to be better defined in order to advance the use of COAs in future clinical trials:
- What symptoms, signs, and functions are important to patients and feasible to measure for meaningful benefit
- What instruments and metrics are available, or could be developed, to perform the measurements accurately
- What type of trial designs are needed to incorporate the measures and instruments into an acceptable endpoint that influences approval
All panels produced extensive background information, providing papers and presentations on the current state of clinical outcomes assessments in neuro-oncology. Relying on panel pre-work; intensive discussion; input from the NCI and FDA, as well as patients and caregivers; and successful models from other disease populations, the Workshop was able to identify existing barriers and develop a framework to enable the development of valid endpoints that take into account COAs, which can be used in drug approval.
“We’ve been funding brain cancer research for 14 years now,” said Max Wallace, CEO, Accelerate Brain Cancer Cure, a Coalition member. “All of that will not matter if there isn’t a clear path to regulatory approval in the field. Although more work needs to be done, we are pleased that this important effort is moving forward and getting the attention not only from the entire field, but also the FDA. This really has the potential to improve patient care going forward.”
The Jumpstarting Brain Tumor Drug Development Coalition is committed to forming a planning group to discuss the consensus points and design a strategy to advance this initiative in coordination with the outcomes of the first Brain Tumor Clinical Trial Endpoints Workshop on imaging-related endpoints.
Additionally, it was made clear to all stakeholders the importance of better including COAs in brain tumor clinical trials so that it becomes common practice. The Jumpstarting Brain Tumor Drug Development Coalition will continue to advocate for the inclusion of COAs into brain tumor clinical trials.
“The brain tumor community can’t wait,” said David Arons, Chief Public Policy & Advocacy Officer, National Brain Tumor Society. “We need better treatments as soon as possible. It is our charge to identify ways to improve clinical research and speed the drug development and approval process in a manner that meets patients’ needs and respects what brain tumor patients and their families are going through. Advancement of COAs through this workshop is part of our strategy to incentivize that process. In that regard, the Coalition applauds the FDA for its clear statement of importance on patient-focused measurement of drug effectiveness and their willingness to provide advice.”
Malignant gliomas, the specific type of brain cancer the Workshops focused on, are simultaneously a life-threatening cancer and a neurological disease, which directly cause a wide range of symptoms. Patients experience rapid decline of physical function, as well as behavioral and neurocognitive changes with tumor progression. Signs, specifically neurocognitive function and self-reported symptoms, have been shown to be predictive of both progression-free and overall survival, making measurement of these indications even more important in a clinical study.
About the Jumpstarting Brain Tumor Drug Development Coalition
The Jumpstarting Brain Tumor Drug Development Coalition is made up of four of the leading brain tumor-focused organizations in the United States, encompassing venture philanthropy; patient advocacy; public policy advocacy; research funding and advancement; education; and representing thousands of patients, caregivers, survivors, clinicians, and researchers. The Coalition aims to achieve the most favorable clinical trials process possible for advancing new treatments for brain tumor patients. Learn more.