Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:

Clinical trials

Early phase clinical trials—are dose expansion cohorts needed?

Nature Reviews Clinical Oncology volume 12, pages 626–628 (2015)Cite this article

Subjects

Dose-expansion cohorts (DECs) enable investigators to identify potentially effective drugs, for specific patient populations, in a single trial by assessing antitumour activity as early as possible. We discuss how the objectives, design and interpretation of DEC have evolved, and how DECs are changing the landscape of early drug development.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Cannistra, S. Challenges and pitfalls of combining targeted agents in phase I studies. J. Clin. Oncol. 26, 3665–3667 (2008).

    Article  CAS  Google Scholar 

  2. Iasonos, A. & O'Quigley, J. Design considerations for dose-expansion cohorts in phase I trials. J. Clin. Oncol. 31, 4014–4021 (2013).

    Article  Google Scholar 

  3. Manji, A. et al. Evolution of clinical trial design in early drug development: systematic review of expansion cohort use in single-agent phase I cancer trials. J. Clin. Oncol. 31, 4260–4267 (2013).

    Article  CAS  Google Scholar 

  4. Motzer, R. J. et al. Nivolumab for metastatic renal cell carcinoma: results of a randomized phase II trial. J. Clin. Oncol. 33, 1430–1437 (2015).

    Article  CAS  Google Scholar 

  5. O'Quigley, J. & Iasonos, A. Bridging solutions in dose finding problems. Stat. Biopharm. Res. 6, 185–197 (2014).

    Article  Google Scholar 

  6. Onar, A., Kocak, M. & Boyett, J. M. Continual reassessment method vs traditional empirically based design: modifications motivated by phase I trials in pediatric oncology by the pediatric brain tumor consortium. J. Biopharm. Stat. 19, 437–455 (2009).

    Article  Google Scholar 

  7. O'Quigley, J., Hughes, M. D. & Fenton, T. F. Dose-finding design for HIV studies. Biometrics 57, 1018–1029 (2001).

    Article  CAS  Google Scholar 

  8. Topalian, S. L. et al. Safety, activity, and immune correlates of anti-PD–1 antibody in cancer. N. Engl. J. Med. 366, 2443–2454 (2012).

    Article  CAS  Google Scholar 

  9. McDermott, D. F. et al. Survival, durable response, and long-term safety in patients with previously treated advanced renal cell carcinoma receiving nivolumab. J. Clin. Oncol. 33, 2013–2020 (2015).

    Article  CAS  Google Scholar 

  10. Iasonos, A. & O'Quigley, J. Working Paper 28: Dose expansion cohorts in phase I trials. Memorial Sloan-Kettering Cancer Center, Deptartment of Epidemiology & Biostatistics Working Paper Series [online], (2014).

    Google Scholar 

Download references

Acknowledgements

This work was partially supported by the NIH (grant numbers R01 CA142859 and and P30 CA008748) and The Translational and Integrative Medicine Research Fund at Memorial Sloan Kettering Cancer Center, NY, USA.

Author information

Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 485 Lexington Avenue, New York, 10065, NY, USA

    Alexia Iasonos

  2. University Pierre and Marie Curie—Paris 6, 4 Place Jussieu, Paris, 75005, France

    John O'Quigley

Authors
  1. Alexia Iasonos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John O'Quigley
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alexia Iasonos.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Iasonos, A., O'Quigley, J. Early phase clinical trials—are dose expansion cohorts needed?. Nat Rev Clin Oncol 12, 626–628 (2015). https://doi.org/10.1038/nrclinonc.2015.174

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrclinonc.2015.174

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing