Statistical design
Toxicity
Sample size was calculated based on a hypothesised 50% improvement in PFS, with 80% power at a 10% 1-sided level of statistical significance (or 90% power at a 20% level of statistical significance), which would require 140 patients to be recruited over 3 years. A hierarchical approach to progression (or not) to a separate phase III study was planned: (i) if there was an observed difference in favour of AZD0530 at the 10% level then this would be an indication to initiate a subsequent phase III study, (ii) if a favourable result was observed at 20% level (but not 10%) then proceeding to phase III trial would only occur if review of the best percentage change in RECIST 1.1 measurement (waterfall plot) supported clinically meaningful activity or (iii) if there was not a statistically significant benefit at 20% level then it would not be worthwhile proceeding to a phase III trial. [Analysis was conducted on an intention-to-treat basis. Survival analysis was performed using the cox proportion hazard model, using a 1-sided p value. Response rates were compared using Pearson’s chi-square test. Toxicity grading analysis was conducted using the Mann–Whitney U test. Data analysis was performed using SPSS and R (version 3.5.1).