Integrated phase II/III clinical trials in oncology: a case study

Clin Trials. 2012 Dec;9(6):741-7. doi: 10.1177/1740774512464724. Epub 2012 Nov 22.

Abstract

Background: Integrated phase II/III trial designs implement the phase II and phase III aspects of oncology studies into a single trial. Despite a body of literature discussing the merits of integrated phase II/III clinical trial designs within the past two decades, implementation of this design has been limited in oncology studies.

Purpose: We provide a brief discussion of the potential advantages and disadvantages of integrated phase II/III clinical trial designs in oncology and provide an example of the operating characteristics of a Radiation Therapy Oncology Group (RTOG) trial.

Methods: We review the differences among proposed integrated phase II/III designs. Then, we illustrate the use of the design in a brain tumor trial to be conducted by the RTOG and examine the impact of association between endpoints on design performance in terms of type I error, power, study duration, and expected sample size.

Results: Although integrated phase II/III designs should not be used in all situations, under appropriate conditions, significant gains can be achieved when using integrated phase II/III designs, including smaller sample size, time and resources savings, and shorter study duration.

Limitations: Data submission without delay and sufficient evaluation of intermediate endpoints are assumed.

Conclusions: Although there are potential benefits in using phase II/III designs, there also may be disadvantages. We recommend running design simulations incorporating theoretical and practical issues before implementing an integrated phase II/III design.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bevacizumab
  • Bias
  • Brain Neoplasms / drug therapy
  • Clinical Trials, Phase II as Topic / methods*
  • Clinical Trials, Phase III as Topic / methods*
  • Data Interpretation, Statistical
  • Endpoint Determination
  • Glioma / drug therapy
  • Humans
  • Lomustine / administration & dosage
  • Research Design*
  • Sample Size
  • Time Factors

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Bevacizumab
  • Lomustine