N A Wages1, C L Slingluff2, G R Petroni1. 1. Department of Public Health Sciences, Division of Translational Research & Applied Statistics, University of Virginia, Charlottesville, Virginia, USA. 2. Division of Surgical Oncology, Department of Surgery, University of Virginia, Charlottesville, USA.
Abstract
Background: In recent years, investigators have asserted that the 3 + 3 design lacks flexibility, making its use in modern early-phase trial settings, such as combinations and/or biological agents, inefficient. More innovative approaches are required to address contemporary research questions, such as those posed in trials involving immunotherapies. Design: We describe the implementation of an adaptive design for identifying an optimal treatment regimen, defined by low toxicity and high immune response, in an early-phase trial of a melanoma helper peptide vaccine plus novel adjuvant combinations. Results: Operating characteristics demonstrate the ability of the method to effectively recommend optimal regimens in a high percentage of trials with reasonable sample sizes. Conclusions: The proposed design is a practical, early-phase, adaptive method for use with combined immunotherapy regimens. This design can be applied more broadly to early-phase combination studies, as it was used in an ongoing study of two small molecule inhibitors in relapsed/refractory mantle cell lymphoma.
Background: In recent years, investigators have asserted that the 3 + 3 design lacks flexibility, making its use in modern early-phase trial settings, such as combinations and/or biological agents, inefficient. More innovative approaches are required to address contemporary research questions, such as those posed in trials involving immunotherapies. Design: We describe the implementation of an adaptive design for identifying an optimal treatment regimen, defined by low toxicity and high immune response, in an early-phase trial of a melanoma helper peptide vaccine plus novel adjuvant combinations. Results: Operating characteristics demonstrate the ability of the method to effectively recommend optimal regimens in a high percentage of trials with reasonable sample sizes. Conclusions: The proposed design is a practical, early-phase, adaptive method for use with combined immunotherapy regimens. This design can be applied more broadly to early-phase combination studies, as it was used in an ongoing study of two small molecule inhibitors in relapsed/refractory mantle cell lymphoma.
Authors: Craig L Slingluff; Gina R Petroni; Walter Olson; Andrea Czarkowski; William W Grosh; Mark Smolkin; Kimberly A Chianese-Bullock; Patrice Y Neese; Donna H Deacon; Carmel Nail; Priscilla Merrill; Robyn Fink; James W Patterson; Patrice K Rehm Journal: J Clin Oncol Date: 2008-09-22 Impact factor: 44.544
Authors: Lei Nie; Eric H Rubin; Nitin Mehrotra; José Pinheiro; Laura L Fernandes; Amit Roy; Stuart Bailey; Dinesh P de Alwis Journal: Clin Cancer Res Date: 2016-06-01 Impact factor: 12.531
Authors: Craig L Slingluff; Gina R Petroni; Kimberly A Chianese-Bullock; Mark E Smolkin; Merrick I Ross; Naomi B Haas; Margaret von Mehren; William W Grosh Journal: J Clin Oncol Date: 2011-06-20 Impact factor: 44.544
Authors: Craig L Slingluff; Gina R Petroni; Walter C Olson; Mark E Smolkin; Kimberly A Chianese-Bullock; Ileana S Mauldin; Kelly T Smith; Donna H Deacon; Nikole E Varhegyi; Sean B Donnelly; Caroline M Reed; Kristy Scott; Nadejda V Galeassi; William W Grosh Journal: Cancer Immunol Immunother Date: 2015-11-18 Impact factor: 6.968
Authors: Nolan A Wages; Craig A Portell; Michael E Williams; Mark R Conaway; Gina R Petroni Journal: Clin Cancer Res Date: 2017-07-21 Impact factor: 12.531
Authors: Brian P Hobbs; Pedro C Barata; Yada Kanjanapan; Channing J Paller; Jane Perlmutter; Gregory R Pond; Tatiana M Prowell; Eric H Rubin; Lesley K Seymour; Nolan A Wages; Timothy A Yap; David Feltquate; Elizabeth Garrett-Mayer; William Grossman; David S Hong; S Percy Ivy; Lillian L Siu; Steven A Reeves; Gary L Rosner Journal: J Natl Cancer Inst Date: 2019-02-01 Impact factor: 13.506