Single arm two-stage studies: Improved designs for molecularly targeted agents.

Area of Science:

• Oncology
• Clinical Trial Design
• Biostatistics

Background:

• Advancements in understanding cancer mechanisms and targeted therapies necessitate stratified medicine.
• Biomarkers are crucial for predicting patient response to molecularly targeted agents.
• Current clinical trial designs require refinement for biomarker-driven studies.

Purpose of the Study:

• To propose a novel, balanced parallel two-stage single-arm phase II trial design for biomarker-driven studies.
• To evaluate the efficiency and performance of the proposed design against existing single-arm trial methodologies.
• To provide recommendations for phase II trial designs when randomization is not feasible.

Main Methods:

• Development of a balanced parallel two-stage single-arm phase II trial design.
• Comparison of the proposed design with sequential enrichment, tandem two-stage, and parallel two-stage designs.
• Utilizing a Bayesian framework to assess the efficiency of data utilization.

Main Results:

• The proposed balanced parallel two-stage single-arm design demonstrates favorable comparison to existing methods.
• The new design offers a more efficient use of collected data within the Bayesian framework.
• The study highlights the limitations of single-arm trials in distinguishing population-level marker prediction from group-specific effects.

Conclusions:

• The proposed balanced parallel two-stage single-arm phase II trial is an efficient approach for biomarker-driven studies.
• Biomarker-driven trials are essential for confirming the stratification capabilities of molecularly targeted agents.
• Sequential enrichment and balanced parallel two-stage designs are recommended for phase II trials lacking randomization.