Interim analysis
toxicity, DLTs
Interim analyses involved the implementation of study stopping rules related to the joint monitoring of efficacy and toxicity using the Bayesian sequential monitoring design of Simon, Thall and Etsey. The DLTs for early stopping were defined as non‐hematologic AEs of grade ≥3 or hematologic toxicity of grade ≥4 (evaluated by CTCAE 4.0). We consider the combination treatment as promising and worthy of future investigation in a larger trial if the response rate is ≥50% and the SAE rate is ≤30%. Study stopping boundaries were calculated based on posterior probabilities of ypRR or SAE rates exceeding prespecified threshold values (representing the expected performance of standard treatment). A run‐in period of 6 patients was used and stopping rules were evaluated every 5 patients thereafter (until a maximum of 36 patients). Based on the observed response rates and SAEs, the study was not halted for early evidence of futility or toxicity and continued till its planned end.