Alliance Plans Adaptive Clinical Trials for Brain Cancer

(DARPA.gov)

12 November 2015. A global collaboration plans a series of clinical trials that address precise molecular targets testing treatments for glioblastoma multiforme, an aggressive brain cancer. The alliance combines medical teams, researchers, and patient advocates to employ adaptive clinical trials, a type of clinical study that enables investigators to adjust research tactics as results with participants come in.

Glioblastoma multiforme is a cancer that forms in the brain’s glial cells, the cells that support the functioning of neurons in the brain sending and receiving nerve signals. The cancer generally grows and spreads quickly, often resulting death within 15 months of diagnosis. American Association of Neurological Surgeons estimates glioblastoma multiforme or GBM occurs in 2 to 3 out of 100,000 adults per year, and accounts for 52 percent of all primary brain tumors. The last new treatment for GBM, temozolomide, was approved in 2005 that in clinical trials, provided about 2.5 additional months of survival time, when combined with radiation therapy.

Because of the lack of progress against GBM, National Biomarker Development Alliance started GBM Adaptive Global Innovative Learning Environment or GBM-Agile. National Biomarker Development Alliance, an organization formed at Arizona State University and located in Scottsdale, sponsors demonstration projects, such as GBM-Agile, that advance the use of biomarkers — molecular indicators — for developing treatments that address an individual’s precise molecular profile.

GBM-Agile aims to conduct a series of clinical trials that adjust their operations as new findings are generated by individuals enrolling in those studies. This kind of trial, known as adaptive clinical trial, makes it possible to alter factors such as treatment regimens or sample sizes based on interim results. This approach seems particularly suited to precision medicine, where treatments are designed to meet the specific molecular profile of participants. It also provides documentation if more extreme steps are needed, such as ending a trial early if no benefits are being recorded or participants are put at risk.

An adaptive trial of potential GBM treatments requires an ethnically diverse population of patients, and as a result GBM-Agile is assembling research and medical teams in the U.S., Germany, Australia, and China, where participants will be recruited. The studies will be designed with Bayesian statistical models, where new data can trigger changes in the conduct of the trials. With this design, GBM-Agile trials aim to incorporate biomarker targets, allowing for more uniform sub-groups of participants, which in turn will allow for more precise testing of individual drugs or combinations of treatments.

The GBM-Agile team is modeling its approach after a similar adaptive trial project for breast cancer, known as I-Spy2. In I-Spy2, patients with breast cancer receive standard chemotherapy, but also experimental treatments aimed at precise molecular targets. The I-Spy2 team says this approach can test new treatments in half the time of conventional clinical studies, with fewer participants, and at a fraction of the cost.

GBM-Agile is also following a clinical trial model approved by FDA known as master protocol, designed for precision medicine studies. Under a master protocol, a single trial design can be employed to test a series of treatments, with participating patients first screened for their biomarker profiles. Participants are assigned to trials where their molecular composition best fits the nature of the treatment being tested, which improves chances of the trial’s success.

So far, more than 100 physicians, scientists, bioinformatics specialists, and patient advocates are taking part in GBM-Agile. The project aims to begin enrolling patients by the middle of 2016, and is raising funds for the trials from foundations and through crowdfunding.

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