'No risk, no fun': challenges for the oncology phase I clinical trial time-performance.

Drug development in oncology is faced with the challenge of making active new compounds available for standard of care in the shortest possible time frame. While rules and regulations create an accepted factor in delaying trial execution, protocol issues and procedures are more often a delay factor than needed, particularly in industry-sponsored studies. This provides an option to decrease trial time, without affecting patient safety. Among the possible rooms for improvement are a balanced use of in- and exclusion criteria, justified by animal toxicology, and flexible dose escalation steps still defined a priori. It is also of crucial importance to make sure in the phase I programme that the pharmacology of the agent involved is appropriately understood. Including real-time pharmacokinetics, food-effect studies and, if possible, bioavailability studies in the phase I programme would decrease the risk of taking the wrong decisions for follow-on development. The concept of increasing the number of study sites to speed up accrual has a negative effect on trial execution and is actually a delay factor that in addition has the intrinsic risk of putting patient safety at stake.