Paul H. Frankel1, Vincent Chung2, Joseph Tuscano3, Tanya Siddiqi4, Jeffrey Longmate1, Susan Groshen5, Edward M. Newman2,6
We seek to reduce the duration of Phase I studies in adult and pediatric cancer studies without violating risk-limits by better accommodating the accrual and evaluation process (“queue”). The processes modeled, the Phase I Queue (IQ), includes patient inter-arrival time, screening, and dose-limiting toxicity evaluation. For our proof-of-principle, the rules of the 3+3 and Rolling 6 Phase I designs were modified to improve patient flow through the queue without exceeding the maximum risk permitted in the parent design. The resulting designs, the IQ 3+3 and IQ Rolling 6, were compared to their parent design by simulation in twelve different scenarios. We demonstrate that IQ designs can reduce the average duration of Phase I studies as compared to their parent designs without changing the risk-limits or MTD selection operating characteristics. These approaches have been successfully implemented in both hematology and solid tumor Phase I studies.
1Division of Biostatistics, City of Hope, 2Department of Medical Oncology, City of Hope, 3Hematology/Oncology, University of California at Davis, 4Hematology and Hematopoietic Cell Transplantation, City of Hope, 5Biostatistics Core, University of Southern California/Norris Cancer Center, 6Division of Molecular Pharmacology/Developmental Cancer Therapeutics Program, City of Hope, Duarte, CA, USA.