Sequential design of phase II-III cancer trials

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 ran...

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Bibliographic Details
Published in:Statistics in medicine 2012-08, Vol.31 (18), p.1944-1960
Main Authors: Lai, Tze Leung, Lavori, Philip W., Shih, Mei-Chiung
Format: Article
Language:English
Subjects:
Antineoplastic Agents - therapeutic use
Bone Neoplasms - secondary
Cancer
Clinical trials
Clinical Trials, Phase II as Topic - methods
Clinical Trials, Phase III as Topic - methods
Computer Simulation
Disease-Free Survival
Failure analysis
generalized likelihood ratio statistics
group sequential clinical trials
Humans
Male
Mathematical models
Medical statistics
Models, Statistical
Neoplasms, Hormone-Dependent - drug therapy
Neoplasms, Hormone-Dependent - pathology
phase II-III designs
Prostatic Neoplasms - drug therapy
Prostatic Neoplasms - pathology
Research Design
Survival analysis
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Summary: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. Copyright © 2012 John Wiley & Sons, Ltd.
ISSN:0277-6715
1097-0258
DOI:10.1002/sim.5346