Purpose: Single-arm phase II trials may not be appropriate for testing cytostatic agents. We evaluate two kinds of randomized designs for the early development of target-based cytostatic agents.
Methods: We compared power of the randomized discontinuation and upfront randomization designs under two models for the treatment effect of targeted cytostatic agents.
Results: The randomized discontinuation design is not as efficient as upfront randomization if treatment has a fixed effect on tumor growth rate or if treatment benefit is restricted to slower-growing tumors. On the other hand, the randomized discontinuation design can be advantageous under a model where only a subset of patients, those expressing the molecular target, is sensitive to the agent. To achieve efficiency, the design parameters must be carefully structured to provide adequate enrichment of the randomly assigned patients.
Conclusion: With careful planning, the randomized discontinuation designs can be useful in some settings in the early development of targeted agents where a reliable assay to select patients expressing the target is not available.