Innovative “adaptive” clinical trial designs are using molecular tools and biomarkers in ways that will streamline research efforts and bring new treatments more quickly to regulatory approval and clinical use.
Innovative “adaptive” clinical trial designs are using molecular tools and biomarkers in ways that will streamline research efforts and bring new treatments more quickly to regulatory approval and clinical use, according to a keynote speaker at the 20th Annual Scientific Meeting of the Society for Neuro-Oncology, held November 19-22 in San Antonio, Texas.
Adaptive clinical trials use biomarkers and study participants’ outcomes on predetermined interim analyses to inform and modify parameters like study drug-arms or dosages to which subsequent patients are assigned-a process that continues throughout the life of a study.
“We look at the data-and that’s not taboo,” said Don Berry, PhD, professor of biostatistics at the University of Texas MD Anderson Cancer Center in Houston.
“Things are happening in-trial and you have to take steps to adapt,” he said, jokingly comparing adaptive clinical trials to a bush pilot leaning out the door of a small airplane to work on the engine mid-flight. “But unlike that pilot, we have protocols and do things prospectively, with if/then statements built into our plans.”
Dr. Berry helped design the I-SPY 2 trial to clinically test multiple promising drugs for high-risk, aggressive breast cancers, matching patients to drugs based on previous experience in the trial. The trial design allows researchers to use data from one group or subgroup of patients to determine which treatments will be used with subsequent participants. The trial uses 10-biomarker signatures and a “never-ending screening process” to achieve that goal. More than 900 patients have been randomized to test the first 10 investigational drugs, he said.
The international GBM Agile (Glioblastoma Multiforme Adaptive Global Innovative Learning Environment) trial takes a similar approach for investigational treatments for GBM, a particularly aggressive form of brain cancer.
GBM Agile will provide “phase II experimental drug screens with many study arms, including combinations and stratification by biomarkers, adaptively randomizing within subtypes vs standard of care to find better therapies,” Dr. Berry explained. “The idea is to provide a solid foundation for focused phase III trials.”
These “small, highly focused trials that match drugs to a biomarker signal” will also allow researchers to learn about off-target effects-and to avoid “huge phase III trials,” he said. “They’re breaking the bank.”
With stratification with biomarkers, adaptive trials evaluate drugs “as per Goldilocks-not too big, not too small, but just right, based on data,” Dr. Berry said.
Each arm of GBM Agile will include no more than approximately 150 patients, he noted.
It’s an approach that Dr. Berry and others have said will turn the traditional clinical trial paradigm “on its head”-but in so doing, will allow personalized drug therapies to reach patients more quickly.
With the increasing expense and poor accrual seen for many traditional clinical trials, this approach has won over a growing number of proponents. Many traditional clinical trials fail, and that is not unique to oncology; Dr. Berry cited 20 recent Alzheimer disease trials that have failed.
“There are cost savings to having a common control arm and the same set of control patients,” he noted.
Drug companies are embracing the new paradigm, patient advocates are getting involved, but others have been slower to do so. “Academia is flunking,” he said. “We have a few ideas but are really taking baby steps. NCI and NIH are limping along.”
“This is an amazing thing we are doing,” Dr. Berry said of adaptive trial efforts. “It’s a completely different way of thinking.”