Skip to main content

Advertisement

SpringerLink
Log in

Evaluating the role of phase I expansion cohorts in oncologic drug development

  • SHORT REPORT
  • Published:
Investigational New Drugs Aims and scope Submit manuscript

Summary

Importance Use of expansion cohorts (EC) in phase I trials is increasing. However, the utility of phase I EC in aiding drug development is unclear. We sought to determine factors associated with the inclusion of EC in phase I studies and the impact of EC on subsequent clinical development. Methods We performed a systematic review of all phase I trials published in the Journal of Clinical Oncology between June 2004 and May 2014. Presence of an EC, number of participants, funding source, class of agent, tumor type, and maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) were identified. Subsequent conduct of phase II studies and FDA approval of the study agent was also assessed. Results We identified 252 phase I studies. An EC was included in 105 studies. Average accrual on EC studies was 47 compared to 31 in studies without EC (p < 0.0001). There was no impact of time on the inclusion of EC. Only 4 % of phase I studies with an EC provided sample size justification. Source of funding had the only significant association with inclusion of EC. Addition of a phase I EC did not impact the phase I MTD/RP2D, subsequent phase II trial, or FDA approval. Conclusion The importance of including an EC in phase I trials is subject to ongoing debate. Our results demonstrated little benefit to including EC in phase I studies. These findings support that innovative design strategies are needed to optimize the utility of EC in phase I studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Ivy SP, Siu LL, Garrett-Mayer E, Rubinstein L (2010) Clin Cancer Res: Off J Am Assoc Cancer Res 16:1726–1736

    Article  Google Scholar 

  2. Eisenhauer EA, O’Dwyer PJ, Christian M, Humphrey JS (2000) J Clin Oncol : Off J Am Soc Clin Oncol 18:684–692

    CAS  Google Scholar 

  3. Boonstra PS, Shen J, Taylor JM, Braun TM, Griffith KA, Daignault S, Kalemkerian GP, Lawrence TS, Schipper MJ (2015) J Natl Cancer Institute 107

  4. Manji A, Brana I, Amir E, Tomlinson G, Tannock IF, Bedard PL, Oza A, Siu LL, Razak AR (2013) J Clin Oncol : Off J Am Soc Clin Oncol 31:4260–4267

    Article  CAS  Google Scholar 

  5. Iasonos A, O’Quigley J (2013) J Clin Oncol : Off J Am Soc Clin Oncol 31:4014–4021

    Article  Google Scholar 

  6. Dahlberg SE, Shapiro GI, Clark JW, Johnson BE (2014) J Natl Cancer Institute 106

  7. Gonen M (2005) Contemp Clin Trials 26:131–140

    Article  PubMed  Google Scholar 

  8. Iasonos A, O’Quigley J (2015) Nature reviews. Clin Oncol 12:626–628

    CAS  Google Scholar 

  9. Iasonos A, O’Quigley J (2016) Stat Med

  10. Rubin EH (2016) In: American Association for Cancer Research Annual Meeting, New Orleans, LA

Download references

Author information

Authors and Affiliations

  1. Division of Pediatric Hematology and Oncology, UH Rainbow Babies & Children’s Hospital, University Hospitals Cleveland Medical Center, 11100 Euclid Avenue, Cleveland, OH, 44106, USA

    Robin E. Norris

  2. Division of Hematology and Oncology, University Hospitals Cleveland Medical Center/Seidman Cancer Center and Case Western Reserve University, Cleveland, OH, USA

    Mohadese Behtaj & Afshin Dowlati

  3. Department of Biostatistics and Epidemiology, Case Western Reserve University and University Hospitals Cleveland Medical Center/Seidman Cancer Center, Cleveland, OH, USA

    Pingfu Fu

Authors
  1. Robin E. Norris
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohadese Behtaj
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pingfu Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Afshin Dowlati
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robin E. Norris.

Ethics declarations

Conflict of interest

Robin Norris declares that she has no conflict of interest. Mohadese Behtaj declares that she has no conflict of interest. Pingfu Fu declares that he has no conflict of interest. Afshin Dowlati declares that he has no conflict of interest.

Funding

The work was supported by the St. Baldrick’s Foundation Scholar (Career Development) Award (R.N.).

Ethical approval

This article is a review of previously published articles and does not contain any new studies with human participants or animals performed directly by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Norris, R.E., Behtaj, M., Fu, P. et al. Evaluating the role of phase I expansion cohorts in oncologic drug development. Invest New Drugs 35, 108–114 (2017). https://doi.org/10.1007/s10637-016-0394-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10637-016-0394-z

Keywords

Search

Navigation