RESTART trial design: two-stage seamless transition design with operational considerations

Area of Science:

• Oncology and Hematology Clinical Trials
• Biostatistics and Clinical Trial Design
• Drug Development and Regulatory Science

Background:

• The oncology/hematology field demands innovative clinical trial designs due to its competitive and rapidly evolving nature.
• Traditional overall survival endpoints can be slow for evaluating early-stage therapies, necessitating alternative approaches.
• Surrogate endpoints are increasingly utilized for accelerated approval of novel cancer treatments.

Purpose of the Study:

• To investigate the logistic and statistical considerations of the proposed RESTART design.
• To introduce a new two-stage, seamless, single- to double-arm Bayesian adaptive design for oncology trials.
• To evaluate the operating characteristics of the RESTART design through simulations.

Main Methods:

• The study proposes the RESTART design, a Bayesian adaptive framework.
• This design facilitates a seamless transition from single-arm dose expansion to a randomized confirmatory study.
• Simulations are used to assess the operating characteristics of the RESTART design.

Main Results:

• The RESTART design is a viable Bayesian approach for oncology trials.
• The design allows for efficient evaluation of novel cancer therapies.
• Simulations demonstrate the feasibility and characteristics of the RESTART design.

Conclusions:

• The RESTART design offers a flexible and efficient adaptive strategy for oncology drug development.
• This Bayesian approach can accelerate the evaluation of early-stage cancer therapies.
• Further research will explore modifications and future directions for the RESTART design.