Accrual Suspensions in Seamless Phase II/III Trials: A Review of NRG Oncology Trials

PURPOSE A phase II/III trial is a type of phase III trial that has embedded in it an intermediate phase II go/no-go decision as to whether to continue the accrual to the phase III sample size. We examine the design characteristics and experience of a well-defined set of National Cancer Institute phase II/III trials, with special emphasis on designed accrual suspensions while awaiting the data to become mature enough for the phase II analysis. This experience is used to highlight the potential of using a calendar backstop to avoid an inordinately long accrual suspension. METHODS We identified all phase II/III trials conducted by NRG Oncology or its precursor National Cancer Institute Cooperative Groups (Radiation Therapy Oncology Group, Gynecologic Oncology Group, and National Surgical Adjuvant Breast and Bowel Project). The design characteristics were recorded, and, for completed trials, the trial results in terms of sample sizes and timing of analyses were tabulated. RESULTS Twenty-two trials were identified, 14 of which had a time-to-event end point for their phase