Two-stage phase II survival trial design

Area of Science:

• Biostatistics
• Clinical Trial Design
• Oncology

Background:

• Advancements in molecularly targeted agents and immunotherapy for relapsed/refractory cancers necessitate robust trial designs.
• Disease progression-free survival (PFS) or event-free survival (EFS) are primary endpoints in phase II cancer trials.
• Current methods for two-stage single-arm phase II trials with time-to-event endpoints are limited by reliance on the exponential distribution.

Purpose of the Study:

• To develop an optimal two-stage design for single-arm phase II trials with time-to-event endpoints.
• To offer a more flexible and powerful alternative to existing methods.
• To accommodate various parametric survival distributions beyond the exponential model.

Main Methods:

• Developed an optimal two-stage design applicable to four common parametric survival distributions.
• Evaluated the performance and advantages of the proposed method compared to existing approaches.
• Focused on enhancing the flexibility of survival model choice and power considerations.

Main Results:

• The proposed two-stage design is more flexible regarding the choice of the underlying survival model.
• The new design adequately addresses the statistical power of the study.
• Demonstrated applicability to commonly used parametric survival distributions.

Conclusions:

• The developed optimal two-stage design provides a flexible and powerful approach for phase II single-arm cancer trials with time-to-event endpoints.
• This method can serve as a valuable complement to established designs like Simon's two-stage design.
• Facilitates more accurate and routine application in clinical trial design for advanced cancer therapies.