Send to

Choose Destination
Contemp Clin Trials. 2016 Mar;47:217-27. doi: 10.1016/j.cct.2016.01.009. Epub 2016 Jan 26.

Innovations for phase I dose-finding designs in pediatric oncology clinical trials.

Author information

National Institutes of Health, Clinical Center, Department of Bioethics, Bethesda, MD, USA. Electronic address:
Gustave Roussy, Pediatric and Adolescent Oncology, Villejuif, France; CNRS UMR8203, Univ. Paris-Sud, Univ. Paris-Saclay, Villejuif, France.
Institut Curie, Pediatric, Adolescent and Young Adults Department, Paris, France.
Gustave Roussy, Biostatistics and Epidemiology unit, Villejuif, France; INSERM U1018, CESP, Univ. Paris-Sud, Univ. Paris-Saclay, Villejuif, France.


Phase I oncology clinical trials are designed to identify the optimal dose that will be recommended for phase II trials. In pediatric oncology, the conduct of those trials raises specific challenges, as the disease is rare with limited therapeutic options. In addition, the tolerance profile is known from adult trials. This paper provides a review of the major recent developments in the design of these trials, inspired by the need to cope with the specific challenges of dose finding in cancer pediatric oncology. We reviewed simulation studies comparing designs dedicated to address these challenges. We also reviewed the design used in published dose-finding trials in pediatric oncology over the period 2009-2014. Three main fields of innovation were identified. First, designs that were developed in order to relax the rules for more flexible inclusions. Second, methods to incorporate data emerging from adult studies. Third, designs accounting for toxicity evaluation at repeated cycles in pediatric oncology. In addition to this overview, we propose some further directions for designing pediatric dose-finding trials.


Adaptive designs; Dose-finding clinical trials; Oncology; Pediatrics; Phase I; Review

[Available on 2017-03-01]
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center