Evaluation of Treatment Effect with Paired Failure Times in a Single-Arm Phase II Trial in Oncology

In early phase clinical trials of cytotoxic drugs in oncology, the efcacy is typically evaluated based on the tumor shrinkage. However, this criterion is not always appropriate for more recent cytostatic agents, and alternative endpoints have been proposed. The growth modulation index (GMI), defned as the ratio between the times to progression in two successive treatment lines, has been proposed for a single-arm phase II trials. The treatment efect is evaluated by estimating the rate of patients having a GMI superior to a given threshold. To estimate this rate, we investigated a parametric method based on the distribution of the times to progression and a nonparametric one based on a midrank estimator. Trough simulations, we studied their operating characteristics and the impact of diferent design parameters (censoring, dependence, and distribution) on them. In these simulations, the nonparametric estimator slightly underestimated the rate and had slightly overconservative confdence intervals in some cases. Conversely, the parametric estimator overestimated the rate and had anticonservative confdence intervals in some cases. The nonparametric method appeared to be more robust to censoring than the parametric one. In conclusion, we recommend the nonparametric method, but the parametric method can be used as a supplementary tool.