Sumithra J Mandrekar
Professor of Biostatistics and Oncology
Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
The design and implementation of precision medicine trials in oncology
Abstract:
With the launch of the National Cancer Institute’s Precision Medicine Initiative in 2015, there has been a shift in trial designs that tailor health care solutions to individual patients’ using a screening platform and move away from the “one-trial / one biomarker at a time” approach. Basket, and umbrella designs represent a class of novel designs for testing targeted therapeutics, and individualizing treatment in oncology. Umbrella trials include a central infrastructure for screening and identification of patients, and focus on a single tumor type or histology with multiple sub trials, each testing a targeted therapy within a molecularly defined subset. Basket trial designs offer the possibility to include multiple molecularly defined subpopulations, often across histology or tumor types, but included in one cohesive design to evaluate the targeted therapy in question. I will discuss the unique characteristics of these designs as well as the challenges encountered in the setting of an umbrella master protocol design using experiences from the ALCHEMIST study in lung cancer. Specifically, I will present the design considerations, as well as logistical details pertaining to the collection of clinical and correlative data for the master protocol and the sub-studies.
Key references:
Govindan R, Mandrekar SJ, Gerber DE, et al. ALCHEMIST Trials: A Golden Opportunity to Transform Outcomes in Early-Stage Non-Small Cell Lung Cancer. Clin Cancer Res. 2015 Dec 15; 21 (24):5439-44
Ou FS, An MW, Ruppert AS, Mandrekar SJ. Discussion of Trial Designs for Biomarker Identification and Validation Through the Use of Case Studies. JCO Precis Oncol. 2019; 3 Epub 2019 Oct 24 PMID: 32190807 PMCID: 7079723
Biography:
Sumithra J. Mandrekar, PhD is currently Professor of Biostatistics and Oncology at the Mayo Clinic, Rochester MN, and the Group Statistician for the Alliance for Clinical Trials in Oncology, which is one of the 4 NCI- funded national clinical trials networks for the conduct of phase II and III clinical trials in adult cancer. She is widely recognized for significant contributions to the statistical methodology for the design, conduct and analysis of clinical trials, particularly in oncology; for leadership in clinical trials and data management coordination at Mayo Clinic and the Alliance for Clinical Trials in Oncology; for leadership on national and international steering committees and advisory panels related to cancer, including the National Cancer Institute Clinical and Translational Advisory Committee (CTAC). She is a fellow and past president of the Society for Clinical Trials. Dr. Mandrekar’s primary research interests include adaptive dose-finding early phase trial designs, designs for predictive biomarker validation, and general clinical trial methodology related to conduct of clinical trials and identification of alternative cancer clinical trial endpoints.
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