Shortening the timeline of pediatric phase I trials: the rolling six design

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Jeffrey M SkolnikPeter C Adamson

Abstract

To shorten the study conduct timeline of pediatric phase I oncology trials by employing a novel trial design. A comparison of the traditional 3 + 3 patients per cohort, phase I trial design with a novel, rolling six design was performed by using discrete event simulation. The rolling six design allows for accrual of two to six patients concurrently onto a dose level based on the number of patients currently enrolled and evaluable, the number experiencing dose-limiting toxicity (DLT), and the number still at risk of developing a DLT. Clinical trial simulations (n = 1,000) were based on historical data and were performed using SAS 9.1.3 (SAS Institute, Cary, NC). Study timelines and patient numbers were determined for each design, and safety was assessed as a function of the number of DLTs observed. In twelve completed historical studies, the median time to study completion was 452 days (range, 220 to 606 days); number of evaluable participants enrolled was 22 (range, 11 to 33), and DLTs occurring per study was three (range, 0 to 5). In 1,000 study simulations, in which the average time to new patient accrual was 10 days, the average +/- standard deviation (SD) time to study completion was 294 +/- 75 days for the rolling six desi...Continue Reading

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