Design of a phase III clinical trial with prospective biomarker validation: SWOG S0819

Mary W. Redman, John J. Crowley, Roy S. Herbst, Fred R. Hirsch, David R Gandara

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

The role of cetuximab in the treatment of advanced non-small cell lung cancer (NSCLC) is currently unclear. The molecular target of cetuximab, epidermal growth factor receptor (EGFR), as measured by FISH, has shown potential as a predictive biomarker for cetuximab efficacy in NSCLC. SWOG S0819 is a phase III trial evaluating both the value of cetuximab in this setting and EGFR FISH as a predictive biomarker. This work describes the decision process for determining the design and interim monitoring plan for S0819. Six possible designs were evaluated in terms of their properties and the hypotheses that can be addressed within the design constraints. A subgroup-focused, multiple-hypothesis design was selected for S0819 that incorporates coprimary endpoints to assess cetuximab in both the overall study population and among EGFR FISH-positive (FISH+) patients, with the sample size determined based on evaluation in the EGFR FISH+ group. The chosen interim monitoring plan specifies interim evaluations of both efficacy and futility in the EGFR FISH+ group alone. The futility-monitoring plan to determine early stopping in the EGFR FISH-nonpositive group is based on evaluation within the positive group, the entire study population, and the nonpositive group. SWOG S0819 uses a design that addresses both the biomarker-driven and generalefficacy objectives of this study.

Original languageEnglish (US)
Pages (from-to)4004-4012
Number of pages9
JournalClinical Cancer Research
Volume18
Issue number15
DOIs
StatePublished - Aug 1 2012

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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