Advocating for Innovative Clinical Trial Design

For many years, clinical oncology research has employed the one-trial-for-one-question model, where a single trial was designed, built, and executed to evaluate a single hypothesis. However, as the field of oncology research grows rapidly with investigational agents and clinical trials, more efficient trial designs are needed to address multiple questions within single trials, and make better use of patient and financial resources. As such, researchers, regulatory agencies, and other key stakeholders have begun exploring fresh ways to evaluate emerging therapies through more productive trial designs. One such forum for these conversations is the Kraft Precision Medicine Accelerator, a collaborative group formed in 2016 that encourages cancer organizations to align on shared goals for a collective impact. Kraft has identified four areas of opportunity: direct to patient, data and analytics, clinical trials, and investment models.

As part of their 2018 Roundtable, Kraft hosted a clinical trials panel on platform trial design on April 11, led by Fortune Magazine editor-in-chief Clifton Leaf. Cancer Research Institute (CRI) consultant and head of clinical alliances Laura Pearce was joined on the panel by Brian Alexander, M.D., MPH, radiation oncologist at Dana Farber Cancer Institute, and Amy McKee, M.D., acting deputy office director, Office of Hematology and Oncology Products, U.S. Food and Drug Administration.

The panel assessed the merits of platform trial design which, unlike the one-trial-for-one-question standard design, explores multiple questions (i.e. therapies or combination therapies) in one trial. Pearce shared her perspective with the Anna-Maria Kellen Clinical Accelerator's approach and its recent shift to platform design and master protocols. The panel members expressed support for innovative protocol design to become a new standard for clinical trials as a way to accelerate and improve efficiencies in the research process. 

Safety and efficacy remained at the heart of the clinical trials discussion, and panelists noted the potential to fast-track promising therapies from trials to FDA approval with platform trial design. As multiple therapies or combinations are investigated in multiple cohorts within the same study, therapies or combinations that don't show benefit can be eliminated from the trial while therapies that demonstrate promising responses are continued and, if applicable, submitted for regulatory approval. Moreover, these trials are adaptable, allowing the addition of new emerging therapies or other adjustments as the science evolves. Approximately 85% of phase 2 therapies transitioning from a platform trial are graduated to FDA approval compared to 30% of phase 2 therapies evaluated in clinical trials using the standard model, which translates to more effective therapies for patients sooner.

As platform and master studies involve greater complexity and challenges in development, build, execution, and multi-stakeholder alliance management, the panel expects that trusted, non-pharmaceutical third-party organizations, like CRI, are best positioned to assume the sponsor and organizer role. CRI and our partners—the Canadian Clinical Trials Group, the Parker Institute for Cancer Immunotherapy, and Ludwig Cancer Research—are currently designing new trials that use adaptive designs and master protocol.