Statistical methods and data analysis
toxicity, death
EVENT, REMISSION, SOLID TUMORS
The intention of the RAMIRIS Phase III trial is to show a superior therapeutic efficacy of the experimental regimen FOLFIRI-Ram compared to the combination of paclitaxel and ramucirumab in patients pretreated with a taxane. Accordingly, the research hypothesis of the study is one-sided. The primary endpoints are OS and ORR according to RECIST. OS is defined as the time from randomization to death from any cause. Further the aim is to compare the ORR in the two groups. ORR is defined as the percentage of patients with complete or partial remission as their best overall response based on Response evaluation criteria in solid tumors 1.1. (RECIST) [A Bonferroni type adjustment of the α error level, due to multiple testing, will be applied. The OS and PFS will be estimated by using the Kaplan–Meier method and logrank test. Hazard ratios will be obtained from corresponding Cox proportional hazard models. ChiAll parameters (except for the co-primary endpoints) will be measured in an explorative or descriptive way. All p values will be two-sided if not explicitly mentioned (co- primary endpoints of phase III). The suitability of the methods will be reevaluated after the data has been received. If required, the statistical method will be adapted accordingly, with critical discussion.OS, ORR, rate of toxicity and other event rates are estimated at pre-defined time points, confidence intervals will be provided. For data analysis Fisher ´s exact test, chiNo formal interim analyses on efficacy or futility are planned for the phase III portion.