title: Sequential design of phase II-III cancer trials.
abstract: Although traditional phase II cancer trials are usually single arm, with tumor response as endpoint, and phase III trials are randomized and incorporate interim analyses with progression-free survival or other failure time as endpoint, this paper proposes a new approach that seamlessly expands a randomized phase II study of response rate into a randomized phase III study of time to failure. This approach is based on advances in group sequential designs and joint modeling of the response rate and time to event. The joint modeling is reflected in the primary and secondary objectives of the trial, and the sequential design allows the trial to adapt to increase in information on response and survival patterns during the course of the trial and to stop early either for conclusive evidence on efficacy of the experimental treatment or for the futility in continuing the trial to demonstrate it, on the basis of the data collected so far.
authors.affiliation: Department of Statistics, Stanford University, Stanford, CA 94305, U.S.A.
authors.forename: Tze Leung
authors.initials: TL
authors.lastname: Lai
authors.forename: Philip W
authors.initials: PW
authors.lastname: Lavori
authors.forename: Mei-Chiung
authors.initials: MC
authors.lastname: Shih
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000556:secondary; D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D003198:Computer Simulation; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D015233:Models, Statistical; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D012107:Research Design
chemical_list: D000970:Antineoplastic Agents