Search

Applications in early-phase cancer trials have motivated the development of many statistical designs since the late 1980s, including dose-finding methods, futility screening, treatment selection, and early stopping rules. These methods are often proposed to address the conventional cytotoxic therapeutics for neoplastic diseases and cancer. Recent advances in precision medicine have motivated novel trial designs, most notably the idea of master protocol (eg, platform trial, basket trial, umbrella trial, N-of-1 trial), for the evaluation of molecularly targeted cancer therapies. In this article, we review the concepts and methodology of early-phase cancer trial designs with a focus on dose finding and treatment screening and put these methods in the context of platform trials of molecularly targeted cancer therapies. Because most cancer trial designs have been developed for cytotoxic agents, we will discuss how these time-tested design principles hold relevance for targeted cancer therapies, and we will delineate how a master protocol may serve as an efficient platform for safety and efficacy evaluations of novel targeted therapies. [ABSTRACT FROM AUTHOR]

Integration of external control data, with patient-level information, in clinical trials has the potential to accelerate the development of new treatments in neuro-oncology by contextualising single-arm studies and improving decision making (eg, early stopping decisions). Based on a series of presentations at the 2020 Clinical Trials Think Tank hosted by the Society of Neuro-Oncology, we provide an overview on the use of external control data representative of the standard of care in the design and analysis of clinical trials. High-quality patient-level records, rigorous methods, and validation analyses are necessary to effectively leverage external data. We review study designs, statistical methods, risks, and potential distortions in using external data from completed trials and real-world data, as well as data sources, data sharing models, ongoing work, and applications in glioblastoma. [ABSTRACT FROM AUTHOR]