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 II component. Thirteen of these 14 trials had designed accrual suspensions. Seven of the eight completed trials had designed accrual suspensions, all of which went on longer than their projected suspension times (3-20 months longer than planned). The trade-offs for using a backstop are discussed using one of these trials as an example.
Conclusion: Phase II/III trials with an accrual suspension and a predefined backstop for the phase II analysis can be a useful tool for minimizing patient exposure to ineffective experimental treatments while still obtaining the trial results in a timely fashion.
© 2024 by American Society of Clinical Oncology.