Abstract OT3-03-03: Challenges faced across borders to open European academic multicentre projects: The ET-FES program part of the ERA-Net TRANSCAN JTC 2011

Abstract

Abstract Background The activation of international non-profit clinical trials funded by the European Commission (EC) is challenging given the cross-borders regulations and the need to follow specific timelines according to EC rules. We report here the logistic procedures and challenges faced by 4 academic centres from 4 different countries from the European Union (EU) for the activation of such program in metastatic breast cancer (MBC). Materials and Methods The primary objective of the ET-FES program is to validate the use of a new radiotracer 18F Fluoroestradiol (FES), targeting estrogen receptors, as a tool to better predict endocrine responsiveness in MBC, with PET/CT. The trial is sponsored by EO Galliera (Genoa, Italy) and brings together Italy, Spain, France and Germany. In 10/2012, ET-FES was approved for funding from EC under the Seventh Framework Programme after the first ERA-NET TRANSCAN Joint Transnational Call (JTC) for Proposals (2011) on validation of new biomarkers for personalized cancer medicine. Results The official start of the program was set up on 06/2013 by the Italian Ministry of Health. Time to institutional review board and to competent authority (CA) approvals were 1.5 and 11, 2 and 5, 3 and 16, and 13 and 14+ months in Italy, France, Spain and Germany respectively. Overall, no blocking comment was raised by the ethical committees; only minor clinical and methodological issues were raised in Germany and Spain. Issues from CA were raised in all countries except France (12, 21 and 23 queries in Italy, Spain and Germany respectively), on quality aspects of 18F-FES investigational medicinal product dossier. At the sponsor level, time to final agreement signature with Advanced Accelerator Applications, the 18F-FES manufacturing company, required 13 months. First patient could be enrolled in Italy 14 and 22 months after ethical committee approval and after the official start of the ET-FES project respectively. Conclusions As of May 2016, of 310 patients expected, only 28 have been enrolled from Italy. From a regulatory viewpoint and acknowledging that 18F-FES does not have yet any marketing approval in the EU, the ET-FES program approval process was timely completed at the ethical committee level in Italy, France and Spain. Time to CA approval varied across countries and was timely achieved only in France, due to requirements varying from CA to CA, stressing the serious lack of harmonized procedures although intended by the 2001/20/EC directive. Regarding sponsor's responsibilities (i.e. Italy), the administrative procedures needed to activate this type of EU projects remain critical, appealing for more tolerant time span in order to satisfy all the legal aspects on contracts by public bodies, according to national rules and laws. One needs to be very conscious of these timelines when applying to EU/EC calls, especially when the time allowed for the conduction of research is limited (3 years here), unless jeopardizing the entire multicentre and multinational effort. Citation Format: Brain E, Corradengo D, Oriana N, Piccardo A, Matteucci F, Cortes J, Harbeck N, Würstlein R, Piris A, Alberini J-L, Merlo DF, Degenhardt T, Turbiez I, Madar O, Monti M, Cesaro A, Rivitti E, Rollandi GA, Iacozzi M, Campazzi E, Campora S, Camporese D, Gennari A. Challenges faced across borders to open European academic multicentre projects: The ET-FES program part of the ERA-Net TRANSCAN JTC 2011 [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-03-03.