Single-Arm Phase II Survival Trial Design Under the Proportional Hazards Model

ABSTRACT

For designing single-arm phase II trials with time-to-event endpoints, a sample size formula is derived for the modified one-sample log-rank test under the proportional hazards model. The derived formula enables new methods for designing trials that allow a flexible choice of the underlying survival distribution. Simulation results showed that the proposed formula provides an accurate estimation of sample size. The sample size calculation has been implemented in an R function for the purpose of trial design. Supplementary materials for this article are available online.

KEYWORDS:

• Contiguous alternative
• One-sample log-rank test
• Proportional hazards model
• Sample size
• Single-arm phase II trial
• Time-to-event

Supplementary Materials

The online supplementary materials contain the R code for the sample size calculated using formula (4) for Table 2.

Acknowledgments

The author acknowledges two anonymous reviewers and an editor for their valuable comments that improved an earlier version of the article.

Funding

The work was supported in part by the National Cancer Institute support grant P30CA021765 and ALSAC.