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Investigational New Drugs

, 27:552 | Cite as

“Classical 3 + 3 design” versus “accelerated titration designs”: analysis of 270 phase 1 trials investigating anti-cancer agents

  • Nicolas PenelEmail author
  • Nicolas Isambert
  • Pierre Leblond
  • Charles Ferte
  • Alain Duhamel
  • Jacques Bonneterre
PHASE I STUDIES

Summary

The number of patients treated at each dose-level in dose seeking phase I trials is arbitrarily established. The most frequently used design is the “classical 3 + 3 design (3 + 3D)”. Recently, Simon et al. had introduced several “accelerated titration designs (ATD)”. In the present analysis, we compared the performance of these two types of designs in 270 recently (1997–2008) published phase I trials. ATD had been used in only 10% of the recent studies. ATD had permitted to explore significantly more dose levels (seven versus five, p = 0.0001) and reduced the rate of patients treated at doses below phase-2 recommended dose (46% versus 56%, p = 0.0001). Nevertheless, ATD did not allow a reduction in the number of enrolled patients, shorten the accrual time nor increase the efficacy of phase I trials. These data support that ATD as an effective clinical trial design over a standard 3 + 3 dose escalation design.

Keywords

Accelerated titration design Dose escalation Method Phase-I-clinical trial 

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Nicolas Penel
    • 1
    • 2
    Email author
  • Nicolas Isambert
    • 3
    • 4
  • Pierre Leblond
    • 5
  • Charles Ferte
    • 1
    • 6
  • Alain Duhamel
    • 2
  • Jacques Bonneterre
    • 6
    • 7
  1. 1.Département de Cancérologie GénéraleCentre Oscar LambretLilleFrance
  2. 2.Equipe d’Accueil 2694: Santé Publique, Epidémiologie et modélisation des maladies chroniquesUniversité Lille IILilleFrance
  3. 3.Département de Cancérologie MédicaleCentre George-François LeclercDijonFrance
  4. 4.Centre d’investigation clinique, CHUDijonFrance
  5. 5.Unité d’Onco-pédiatrieCentre Oscar LambretLilleFrance
  6. 6.Département Universitaire de SénologieCentre Oscar LambretLilleFrance
  7. 7.Département Universitaire de Cancérologie, Faculté de MédecineUniversité de Lille IILilleFrance

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