How the european clinical trial directive impacts trial implementation: lines, on behalf of siopen cooperative group

Objectives: European Low and Intermediate Risk Neuroblastoma (LINES, EudraCT: 2010-021396-81, ClinicalTrials.gov Identifier: NCT01728155) is an international SIOPEN clinical trial, in the framework WP10 (ENCCA PROJECT: European Network for Cancer research inChildren and Adolescents). LINES stratifies patient’s treatment according to biological and clinical markers in order to: i) minimize the treatment burden in those low-risk patients who in previous studies were shown to have an excellent long-term outcome, ii) intensify treatment inthose patients with biologically unfavourable but not MYCN amplified neuroblastoma to improve outcome. Methods: LINES includes ten separate therapeutic groups, one of them randomised. All the cases are registered at Siopen-r-net database with check-points to monitor the quality of prospectively entered staging data, including real time central review for biology andhistology. Neonatal adrenal masses (NAM) in infants below 3 months are also registered and observed, without initial surgery.Results: LINES trial-sponsored by IIsLaFE was first launched in Spain (28 sites) in July 2011 and it was opened in Italy (21 sites), Austria (5 sites) and Denmark (3 sites) in 2012. Then,France (29 sites), Norway (4 sites), Israel (1 site) and Belgium (2 sites) were authorized in2013. Switzerland, Ireland, Slovenia and New Zeeland are expected to be authorized in thecoming months. In summary, only 8 of 21 expected participating countries have been openedfor recruitment and 142 patients have been enrolled and grouped (73 low risk, 32 intermediaterisk and 37 NAM) in the last 2.5 years.Conclusions: Since European Clinical Trial Directive 2001/20/EC implementation, it hasbeen very difficult to launch academic pediatric cancer trials due to high cost, additionalnational requirements and bureaucracy, delaying clinical trial initiation. We hope the newClinical Trial Regulation will bring a process of harmonisation and shorten timelines acrossEurope.Acknowledgements: FP7 2007-2013_project ENCCA grant agreement-no-261743.