title: A Phase I/II adaptive design for heterogeneous groups with application to a stereotactic body radiation therapy trial.
abstract: Dose-finding studies that aim to evaluate the safety of single agents are becoming less common, and advances in clinical research have complicated the paradigm of dose finding in oncology. A class of more complex problems, such as targeted agents, combination therapies and stratification of patients by clinical or genetic characteristics, has created the need to adapt early-phase trial design to the specific type of drug being investigated and the corresponding endpoints. In this article, we describe the implementation of an adaptive design based on a continual reassessment method for heterogeneous groups, modified to coincide with the objectives of a Phase I/II trial of stereotactic body radiation therapy in patients with painful osseous metastatic disease. Operating characteristics of the Institutional Review Board approved design are demonstrated under various possible true scenarios via simulation studies.
authors.affiliation: Division of Translational Research & Applied Statistics, Department of Public Health Sciences, University of Virginia, Charlottesville, 22908, VA, USA.
authors.forename: Nolan A
authors.initials: NA
authors.lastname: Wages
authors.affiliation: Department of Radiation Oncology, University of Virginia, Charlottesville, 22904-4135, VA, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Read
authors.affiliation: Division of Translational Research & Applied Statistics, Department of Public Health Sciences, University of Virginia, Charlottesville, 22908, VA, USA.
authors.forename: Gina R
authors.initials: GR
authors.lastname: Petroni
mesh_terms: D001859:Bone Neoplasms / Q000556:secondary / Q000601:surgery*; D017321:Clinical Trials, Phase I as Topic / Q000379:methods / Q000706:statistics & numerical data*; D017322:Clinical Trials, Phase II as Topic / Q000379:methods / Q000706:statistics & numerical data*; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D006801:Humans; D015233:Models, Statistical; D010166:Palliative Care; D011832:Radiation Injuries / Q000209:etiology / Q000517:prevention & control; D016634:Radiosurgery / Q000009:adverse effects / Q000706:statistics & numerical data*; D011879:Radiotherapy Dosage; D012107:Research Design / Q000706:statistics & numerical data*; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome
keywords: Phase I; Phase I/II; adaptive design; dose-finding; heterogeneity; optimal dose