Clinical trial methodology in rare gynecologic tumor research: Strategies for success

Background: Performing clinical trials in rare gynecologic cancers presents specific challenges. Strategies for improving accrual and modifications in clinical trial design are outlined. Methods: The literature was reviewed in order to present statistical designs pertinent to the study of rare gynecologic cancers. The experience of the Gynecologic Oncology Group/NRG Oncology is outlined as it relates to rare gynecologic cancer clinical trial development. Results: Significant progress has been made in studying rare tumors, both nationally and in gynecologic oncology, but challenges inherent to the study of uncommon diseases remain. Important components of these trials include establishing the standard of care, utilizing the appropriate clinical trial design to effectively answer the question in the trial, accurately estimating sample size, choosing modified and realistic endpoints, and avoiding pitfalls specific to rare tumors. Adaptive trial design and statistical modifications are important components of clinical trial design in rare tumors. Conclusion: Strategies for effective study of rare gynecologic cancers must be implemented when designing clinical trials for these patients.