title: Design of Phase II cancer trials for evaluation of cytostatic/cytotoxic agents.
abstract: For experimental anticancer agents that may have both cytostatic and cytotoxic effects, assessment of response rates alone may not capture the full impact of the treatment. Oncologists are therefore interested in assessing both response and stable disease rates in early phase clinical trials of such therapies. We describe the design of a single-arm, Phase II clinical trial for the simultaneous evaluation of objective response and stable disease (lack of early tumor progression) rates using standard RECIST criteria. Demonstration of a sufficiently high rate for either of these endpoints will lead to rejection of the null hypothesis and a conclusion that the treatment warrants further study. A design is chosen that satisfies the desired type I error constraint and has sufficient statistical power at several selected points within the alternative hypothesis space using a restricted search algorithm. An early stopping rule for lack of efficacy is incorporated. The method is illustrated by the design of a Phase II clinical trial in head and neck cancer.
authors.affiliation: Department of Health Studies, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Masha
authors.initials: M
authors.lastname: Kocherginsky
authors.forename: Ezra E W
authors.initials: EE
authors.lastname: Cohen
authors.forename: Theodore
authors.initials: T
authors.lastname: Karrison
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic / Q000379:methods* / Q000706:statistics & numerical data; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D012107:Research Design / Q000706:statistics & numerical data
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; C504878:enzastaurin