BETHESDA, Md.—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.
The brain tumor clinical trial endpoints workshop focusing on clinical outcomes assessments (COAs)—measurements of how a brain tumor patient feels and functions—was the second of a two-part series of workshops in 2014. The first workshop was on imaging-measured endpoints for glioblastoma. Both workshops were sponsored by the Jumpstarting Brain Tumor Drug Development Coalition, which is made up of the National Brain Tumor Society, Accelerate Brain Cancer Cure, Society for Neuro-Oncology and Musella Foundation for Information and Research. Attendees represented pharmaceutical companies, the U.S. Food and Drug Administration (FDA), the National Cancer Institute, leaders in neuro-oncology and neurology research and clinical care, nonprofits, patients, advocates and caregivers.
The workshop was conceived in a meeting with the FDA’s Office of Hematology and Oncology Drug Products that discussed the need to better understand the state of the field in brain tumor clinical trial endpoint measurements, including endpoints related to survival, progression, symptoms, function and cognition. Leaders in the field believed that COAs 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, who was the 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.”
She continued, “As a patient advocacy organization, National Brain Tumor Society knows that the brain tumor community wants therapies that both extend life and improve it while they fight the disease. Thus it was important to have the second workshop that put a focus on how to improve clinical outcome measures to determine if investigational drugs are reducing some of the terrible symptoms of brain tumors and also enabling patients to function and think.”
The neuro-oncology community has long recognized that COAs are important, according to David Arons, chief public policy and advocacy officer of the National Brain Tumor Society. He explained that all the stakeholders needed a process to learn from each other, come to an understanding of the state of the field and determine ways to improve the usefulness of COAs and improve the accuracy of data collection.
The conference emphasized 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 Arons. “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.”
Malignant gliomas, the specific type of brain cancer that was the focus of the workshops, 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.
The first workshop focused on imaging endpoints. One of its outcomes was an agreed-upon action item by all stakeholders that standardization of imaging data acquisition in brain tumor clinical trials is critical and an effort needs to be led in this area. Following the workshop, the Jumpstarting Brain Tumor Drug Development Coalition formed the Brain Tumor Imaging Standardization Steering Committee to develop a basic standardized imaging data acquisition protocol that has the consensus support from the community.
“We have achieved that through the hard work and collaboration of members of the committee that come from neuro-radiology, neuro-oncology, patient advocacy, NCI and FDA,” Armstrong said.
“This new consensus agreement on new, standard basic imagining acquisition protocol will allow regulators to have more confidence in the imagining data that is collected in clinical trials,” Arons added.
The second workshop, on COAs, produced a consensus view that there need to be validated COAs for a few priority symptoms, signs and functions, and those tools should be used across trials. The coalition is working on a planning process to reach this goal and improve the use of COAs as supportive endpoint measurements for brain tumor clinical trials seeking survival as a primary endpoint.
