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

Investigational New Drugs
Nicolas PenelJacques Bonneterre

Abstract

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.

References

Jan 1, 1990·Annals of Oncology : Official Journal of the European Society for Medical Oncology·G DecosterE E Holdener
May 1, 1995·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·C DaughertyM Siegler
Aug 6, 1997·Journal of the National Cancer Institute·R SimonM C Christian
Apr 13, 2000·Annals of Oncology : Official Journal of the European Society for Medical Oncology·T BachelotM Clavel
Aug 28, 2003·JAMA : the Journal of the American Medical Association·Manish Agrawal, Ezekiel J Emanuel
Nov 4, 2004·JAMA : the Journal of the American Medical Association·Thomas G RobertsJeffrey W Clark
Jun 9, 2006·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A MorabitoF Perrone
Sep 25, 2007·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Christopher M BoothElizabeth A Eisenhauer
Sep 25, 2007·Investigational New Drugs·Nicolas PenelJacques Bonneterre
Oct 28, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Jaap Verweij

❮ Previous
Next ❯

Citations

Feb 2, 2010·Investigational New Drugs·Nicolas PenelJocelyne Bérille
Nov 11, 2015·Nature Reviews. Clinical Oncology·Kit Man WongS Gail Eckhardt
Apr 30, 2013·Critical Reviews in Oncology/hematology·Revathi Ananthakrishnan, Sandeep Menon
Feb 18, 2014·British Journal of Clinical Pharmacology·David GuédéRichard Peck
Feb 24, 2015·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Katharine A NicholsonJames D Berry
Mar 27, 2013·Clinical Trials : Journal of the Society for Clinical Trials·Antje HoeringJohn Crowley
May 21, 2015·American Society of Clinical Oncology Educational Book·Kit Man WongS Gail Eckhardt
Feb 9, 2012·American Journal of Clinical Oncology·Samantha CaldwellGlen J Weiss
Jan 27, 2019·Molecular Cancer Therapeutics·Akihiko ShimomuraMakoto Nishio

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
J Verweij
Journal of the National Cancer Institute
Sarah Zohar, John O'Quigley
© 2021 Meta ULC. All rights reserved