124IN - Phase I cancer drug development in Europe

Date 27 September 2014
Event ESMO 2014
Session ESMO-CSCO: Global collaboration in phase I cancer drug development
Topics Drug Development
Bioethics, Legal, and Economic Issues
Presenter Jean-Charles Soria
Citation Annals of Oncology (2014) 25 (suppl_4): iv43-iv44. 10.1093/annonc/mdu318
Authors J. Soria
  • Dept. Of Medicine, Institut de Cancérologie Gustave Roussy, 94805 - Villejuif CEDEX/FR




Early drug development (EDD) in Europe is today very much in line with EDD in the USA in terms of regulatory process, timelines, and methodological approaches. However in Europe, approval for clinical trials of new agents is the responsibility of each member state, with each country providing its own regulatory authority. In that same direction the EU Clinical Trials Directive (CTD) provides the principles (derived from ICH-GCP), which are however interpreted and converted to law separately by each member state (1). While historically cooperative groups used to be strong stakeholders of EDD in the EU (ie, the Early Clinical Trials Group of the EORTC, SENDO, the Experimental Cancer Medicine Network of Cancer Research UK, CESAR), there is a clear trend towards the emergence of individual phase I centers where the expertise and the reputation for the conduct of these studies has been firmly established. Among those centers, the largest ones (by number of new patients enrolled in phase I/year) encompass: the Drug Development Unit at The Royal Marsden in London, the Vall D'Hebron Institute of Oncology in Barcelona, and the Drug Development Department (DITEP) at Gustave Roussy in Paris. Recently a retrospective analysis of phase I data from 14 European Institutions has demonstrated that phase I trials are characterized by a 50% likelihood of patient benefit (ie PR, SD) and a very low risk of toxic death (0.5%) (2). In collaboration with pharmaceutical companies and academia, an EORTC-led initiative, DLT-TARGETT, collected data encompassing 24 918 adverse events from 2084 patients included in 54 completed phase 1 trials. This initiative concluded that a) dose-increment recommendation need to take into account all available information, notably DLTs observed beyond cycle 1 in prior (and current, if feasible) dose levels b) any toxicity – whatever the grade - leading to a significant decrease in RDI should deserve particular attention c) the Recommended Dose for further studies should incorporate all available information - notably toxicities observed after C1 and intolerable clinical G2 toxicities - and be based on achieving > 75% RDI (3) References 1. Forster M et al. Clinical Cancer Research 2010 2. Olmos D et al. Journal of Clinical Oncology. 2012 3. Postel Vinay et al. European Journal of Cancer 2014.


The author has declared no conflicts of interest.