There are many new ideas for incorporating radiation therapy into treatment regimens and numerous novel compounds that might be useful in combination with radiation therapy. Furthermore, the growing molecular characterization of cancer and the expansion of advanced imaging techniques offer the potential for unique biomarker development. Given the enormous range of possible radiation, drug, and biomarker combinations, the conventional clinical trial paradigms that were designed for testing a single hypothesis may not be flexible or efficient enough to deal with future clinical questions. Adaptive trials, for instance the use of Bayesian statistical frameworks, are an exciting innovation that offers the potential to address some of inefficiencies and inflexibilities of the conventional clinical trial effort. There are already multiple large clinical trials that utilize these principles. With increasing acceptance from industry and regulators the number of trials using these paradigms will likely increase in the next decade. This session is dedicated to highlighting some of the underlying principles of adaptive clinical trial design and to illustrate potential scenarios where these types of designs might prove useful. At the conclusion of this activity, the learner will be able to do the following: 1. Explain the rationale and need for innovation in clinical trial design. 2. Recognize the basic differences between frequentist and Bayesian methods. 3. Identify major ongoing trials using innovative trial designs.