Invited Session 5: Trial Design for Rare Diseases/Childhood Cancer

Chair: Alexander Drilon MSKCC

Conducting Clinical Trials for Rare Genomic Subsets of Cancer

Speaker: Alexander Drilon, MSKCC

Alexander Drilon Dr. Alexander Drilon is the Chief of the Early Drug Development Service and an Associate Attending Physician of the Thoracic Oncology Service at Memorial Sloan Kettering Cancer Center in New York. His research focuses on the development of targeted therapy for genomic subsets of lung cancer and other solid tumors, including cancers that harbor fusions involving ALK, ROS1, RET, and NTRK1/2/3, and MET exon 14 skipping alterations. He is a recipient of American Society for Clinical Oncology (ASCO)/Conquer Cancer Foundation Career Development and Young Investigator Awards, and grants from the National Institutes of Health/National Cancer Institute, International Association for the Study of Lung Cancer, LUNGEVITY, and the Lung Cancer Research Foundation.

Abstract

TBA


Dynamic Precision Medicine for Rare and Pediatric Cancers

Speaker: Robert Beckman, Georgetown University Medical Center

Robert Beckman Robert Beckman, M.D., Professor of Oncology and of Biostatistics, Bioinformatics, and Biomathematics at Georgetown University Medical Center, is an oncology clinical researcher and mathematical biologist who has played significant leadership roles in developing new oncology clinical research groups at 4 pharmaceutical companies and in 5 cross-company collaborations, and brought 23 new oncology therapies into man, and 2 to market. He has co-invented novel clinical study designs and development strategies for oncology and rare diseases, and leads the Drug Information Association Innovative Design Scientific Working Group, a 250-person international group in this field. Dr. Beckman’s theoretical studies of cancer evolution predicted broad features of tumor evolution before experimental results were available, and have more recently led to a new approach to cancer precision medicine, dynamic precision medicine, which holds promise for significant improvement in patient outcomes. Dr. Beckman’s versatile publication record of over 300 articles, patents, and presentations ranges from computational chemistry to clinical oncology, emphasizing quantitative approaches.


An Optimal Two-Period Multiarm Platform Design with New Experimental Arms Added During the Trial

Speaker: Haitao Pan, St. Jude Children’s Research Hospital

Haitao Pan Dr. Pan is an Assistant Professor of Biostatistics at St. Jude Children’s Research Hospital. His research focuses on innovative clinical trials design especially for oncology from early to late phases. Since joining St. Jude in 2017, he has served as the Primary Study Statistician for 32 St. Jude investigator–initiated clinical trials. He serves on the Clinical Trials – Scientific Review Committee at St. Jude. Dr Pan is author of 50+ publications in peer-reviewed journals including across medical and statistical journals and a published book by Springer Nature. He has also developed 13 software packages/applications, with focus on adaptive clinical trials design and sample-size calculation, some of which have been used to develop clinical trial protocols at St. Jude. He is also an adjunct faculty at Florida State University and The University of Memphis. Dr Pan holds two Ph.D.; one is in Preventive Medicine in China and another Ph.D. in Biostatistics from MD. Anderson Cancer Center.

Abstract

Platform trials are multiarm clinical studies that allow the addition of new experimental arms after the activation of the trial. Statistical issues, with respect to ”adding new arms”, however, have not been thoroughly discussed. This work was motivated by a ”two-period” pediatric osteosarcoma study, which will start with two experimental arms and one control arm and later add two more pre-planned experimental arms. The one common control arm will be shared among experimental arms across the trial. In this presentation, we introduce a principled approach, including, how to modify the critical boundaries to control the family-wise error rate when new arms are added, how to re-estimate the sample size and provide the optimal control-to-experimental arms allocation ratio, in terms of minimizing the total sample size to achieve a desirable power. The influence of the timing when new arms are added to the design’s operating characteristics is also examined, which provides a practical guide for deciding the timing of adding new arms. Other various numerical evaluations have also been conducted. Method of controlling the PWER has also been proposed. We have developed a R package, PlatformDesign, for practitioners to easily use this platform trial approach. A detailed step-by-step tutorial is provided in vignette.


Considerations for Clinical Trials in Patients with Rare Cancers

Speaker: Brigitte C. Widemann, NCI

Brigitte Widemann As chief of NCI’s POB Dr. Widemann oversees and active basic, translational and clinical research program for children and young adults with hematologic and solid malignancies. She joined the NCI in 1992 as a pediatric hematology oncology fellow after having obtained her MD and completed pediatric residency at the University of Cologne in Germany. Her research has been focused on drug development and early clinical trials for children with refractory solid tumors or genetic tumor predisposition syndromes, in particular neurofibromatosis type 1 (NF1). The work of her research team on NF1 resulted in the first U.S. FDA approved medical therapy, the MEK inhibitor selumetinib, for children with NF1 and inoperable, symptomatic plexiform neurofibroma. She received tenure at the NIH in 2009 and became the Chief of the POB in 2016. Dr. Widemann is a member of the Association of American Physicians and recipient of the AACR-Joseph H. Burchenal Award for Outstanding Achievement in Clinical Cancer Research. She serves as special advisor to the NCI Director for childhood cancer and has authored more than 200 original scientific papers, reviews, book chapters, and conducted many clinical trials.