Abstract
In oncology, next generation sequencing and comprehensive genomic profiling have enabled the detailed classification of tumors using molecular biology. However, it is unrealistic to conduct phase I–III trials according to each sub-population based on patient molecular subtypes. Common protocols that assess the combination of several molecular markers and their targeted therapies by means of multiple sub-studies are required. These protocols are called “master protocols,” and are drawing attention as a next-generation clinical trial design. Recently, several reviews of clinical trials based on the master protocol design have been published, but their definitions of these such trials, including basket, umbrella, and platform trials, were not consistent. Concurrently, the acceleration of the development of new statistical designs for master protocol trials has been underway. This article provides an overview of recent reviews for master protocols, including their statistical design methodologies in Oncology. We also introduce several examples of previous and on-going master protocol trials along with their classifications by some recent studies.
Highlights
In oncology, generation sequencing and comprehensive genomic profiling have enabled detailed classification of tumors using molecular biology
We introduce several examples of master protocol trials along with their classifications according to previous studies
Clinical trials that used the marker-stratified design include the INTEREST [29] and MARVEL [30] trials. After this type of design was introduced, sequential subgroup-specific, marker sequential test (MaST) and fallback designs were proposed as extensions of the marker-stratified design [31]; this eventually led to the proposal of clinical trials that use the master protocol design
Summary
Generation sequencing and comprehensive genomic profiling have enabled detailed classification of tumors using molecular biology With this development, targeted therapies are being established for some tumor types based on genetic mutations [1,2,3,4,5,6,7,8,9]. Common protocols that assess the combination of several molecular markers and their targeted therapies by means of multiple sub-studies are required for single and/ or multiple tumor types. These protocols are called “master protocols,” and are drawing attention as a next-generation clinical trial design. We discuss new statistical designs for basket trials, including designs that use the recently developed response-adaptive randomization, in addition to discussing the future direction of master protocol trials
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