Most oncology social workers (OSWs) are at least somewhat familiar with clinical trials, the systematic process by which research ideas move from bench to clinic while researchers carefully gather sufficient data to determine whether a new approach is as good as or better than the current standard of care. Historically, this has been a lengthy, expensive process. A new drug may be in development for 10 years before receiving approval from the Food and Drug Administration (FDA), and average research costs are estimated to be between $650 million and $2 billion for each drug ( Prasad & Mailankody, 2017 ).

Moreover, randomized control trials (RCTs), considered the gold standard of research trials, typically only evaluate one drug or treatment protocol at a time. These exorbitant development costs can stymie research in all areas, but they are particularly difficult to overcome with rare diagnoses such as glioblastomas (GBMs, the most common and aggressive type of malignant brain tumor) and pancreatic cancer.

A relatively new type of trial methodology called a “platform trial” is expediting research on brain tumors and other rare diseases. Instead of the typical RCT methodology that randomizes participants to one of only two “arms,” one being the standard of care and the other being the new “experimental” option, platform trials have one control but many experimental groups that allow for testing of a number of drugs at the same time. Additionally, platform trials incorporate complex statistical methods that allow the trial to determine “futility” (a drug deemed not as good as standard of care) more quickly and direct new enrollees to other arms of the trial.

One example of a platform trial is the GBM AGILE (Glioblastoma Adaptive Global Innovative Learning Environment) trial for patients with both newly diagnosed and first recurrence GBMs. GBM AGILE is a combined Phase II (Efficacy and Safety) and Phase III (Confirmatory) “adaptive” platform trial. Its goal is to identify effective therapies and the most promising biomarker-defined populations for those therapies. GBM AGILE is testing multiple therapies concurrently against a common control (standard of care). This enables more patients on trial to get access to experimental therapies. The intent is to lower the cost, time and number of patients required to evaluate potentially effective therapies for GBM.

GBM AGILE uses “adaptive randomization” to dynamically adjust how treatments are assigned to patients. If one treatment arm out-performs another, a higher proportion of new participants are assigned to that treatment arm. Similarly, if an arm is under-performing, that arm will initially receive fewer of the new enrollees, and if poor performance continues, the treatment being tested by that arm will be declared ineffective and that arm of the trial closed.

Another unique aspect of the GBM AGILE trial is that it is sponsored by the Global Coalition for Adaptive Research (GCAR), an international nonprofit partnership comprised of clinical, translational and basic science investigators. GCAR is enabling the GBM AGILE platform trial to be opened all over the world and hopes to be able to test the most promising treatments without undue influence from for-profit entities. For more information about GBM AGILE, see https://www.gcaresearch.org/gbm.agile/about/.

Platform trials bring much needed hope to individuals affected by GBMs and other rare diseases where treatment advancements have historically been slow. For instance, the current chemotherapy of choice for most malignant brain tumors is Temozolomide, which received FDA approval in 1999. Since then, there has been depressingly little progress in the treatment of malignant brain tumors (although genomics have allowed for more personalized medicine). Platform trials are just taking off in oncology, but if they are able to accomplish the goals of decreasing costs, time and number of patients needed for trials, they will indeed change the face of cancer research.

Reference

Prasad, V., & Mailankody, S. (2017). Research and development spending to bring a single cancer drug to market and revenues after approval. JAMA Internal Medicine, 177(11), 1569-1575. doi:10.1001