PURPOSE Novel Bayesian adaptive designs provide an effective way to improve clinical trial efficiency. These designs are superior to conventional methods, but implementing them can be challenging. The aim of this article was to describe what we learned while applying a novel Bayesian phase I-II design in a recent trial. METHODS The primary goal of the trial was to optimize radiation therapy (RT) dose among three levels (low, standard, and high), given either with placebo (P) or an investigational agent (A), for treating locally advanced, radiation-naive pancreatic cancer, deemed appropriate for RT rather than surgery. Up to 48 patients were randomly assigned fairly between RT plus P and RT plus A, with RT dose-finding done within each arm using the late-onset efficacy-toxicity design on the basis of two coprimary end points, tumor response and dose-limiting toxicity, both evaluated at up to 90 days. The random assignment was blinded, but within each arm, unblinded RT doses were chosen adaptively using software developed within the institution. RESULTS Implementing the design involved double-blind balance-restricted random assignment, real-time assessment of patient outcomes to evaluate the efficacy-toxicity trade-off for each RT dose in each arm to optimize each patient's RT dose adaptively, and transition from a single-center trial to a multicenter trial. We present lessons learned and illustrative documentation. CONCLUSION Implementing novel Bayesian adaptive trial designs requires close collaborations between physicians, pharmacists, statisticians, data managers, and sponsors. The process is difficult but manageable and essential for efficient trial conduct. Close collaboration during trial conduct is a key component of any trial that includes real-time adaptive decision rules.