Carrle The Eur opean and Am erican O steosarcoma S tudy EURAMOS-1 A successful transatlantic cooperation in Osteosarcoma D Carrle, S Bielack, M Sydes, T Butterfass-Bahloul, G Calaminus, G Jovic, N Marina, A Oellers M Perisoglou, S Smeland, J Whelan, M Bernstein Supported by the European Science Foundation under the EUROCORES Programme European Clinical Trials (ECT) Sixth Framework Programme, under Contract no: ERAS-CT of the European Commission DG Research FP6

Carrle EURAMOS-1: Study objectives 2 Focuses:  Scientific: Improve treatment results: Poor responder: Salvage therapy (+/- HD-Ifo/Eto) Good reponder: Maintenance therapy (+/- Peg-Interferon)

Carrle EURAMOS-1: Study objectives 2 Focuses:  Scientific: Improve treatment results: Poor responder: Salvage therapy (+/- HD-Ifo/Eto) Good reponder: Maintenance therapy (+/- Peg-Interferon)  Feasibility of international collaborations

Carrle Disclaimer This presentation is not about survival data of EURAMOS-1 but about other relevant outcome from a large multinational clinical trial

Carrle Osteosarcoma: 5-Year Survival Osteosarcoma: Internat study results Stiller et al EJC 2006Mirabello et al Cancer 2009

Carrle Osteosarcoma: 5-Year Survival Survival plateau Osteosarcoma: Internat study results Stiller et al EJC 2006Mirabello et al Cancer 2009

Carrle Osteosarcoma: 5-Year Survival Survival plateau Slow Progress Osteosarcoma: Internat study results Stiller et al EJC 2006Mirabello et al Cancer 2009

Carrle Osteosarcoma: 5-Year Survival Survival plateau Slow Progress Salvage-question unresolved Osteosarcoma: Internat study results Stiller et al EJC 2006Mirabello et al Cancer 2009

Carrle Osteosarcoma: 5-Year Survival Survival plateau Slow Progress Salvage-question unresolved Osteosarcoma: Internat study results Stiller et al EJC 2006Mirabello et al Cancer 2009

Carrle Osteosarcoma: 5-Year Survival Survival plateau Slow Progress Salvage-question  700 poor responders  2000 patients Osteosarcoma: Internat study results Stiller et al EJC 2006Mirabello et al Cancer 2009

Carrle years Multiinst. Osteosarcoma Studygroups Study duration (years) for recruitment of 2000 patients COG COSS EOI SSG SFOP 166/y 80/y 53/y 52/y 33/y

Carrle Multiinst. Osteosarcoma Studygroups Study duration (years) for recruitment of 2000 patients COG COSS EOI SSG SFOP 166/y 80/y 53/y 52/y 33/y years

Carrle EURAMOS-countries : Potential recruitment 583 Mio = 8.7% of world population Osteosarkom-Inc. ≈2-3 per Mio/Year ≈50% eligible  730/year

Carrle Pro International collaboration EURAMOS Scientific rationale Rapid accrual –> quicker results + answers  Improve Cure Rate Hawkins D J Ped Hem 2004 Trimble et al JCO 2009

Carrle Pro International collaboration EURAMOS Scientific rationale Rapid accrual –> quicker results + answers  Improve Cure Rate Additional infrastruc- ture requirements Differing regulations Money  no uniform funding,  more costly Pragmatism Less glory per investi- gator Contra Trimble et al JCO 2009 Hawkins D J Ped Hem 2004

Carrle EURAMOS-group 1st. Meeting Brisbane 2001

Carrle EURAMOS-group 1st. Meeting Brisbane 2001 Research and Development Department

Carrle Research and Development Department Crazy Dreamer Division EURAMOS-group 1st. Meeting Brisbane 2001

Carrle SSG COG EOI COSS EURAMOS: Pan-European/American Collaboration 4 studygroups - 15 countries -

Carrle Office for Human Research Protections (OHRP) Federalwide Assurance (FWA) assurance of compliance with the federal regulations for the Protection of Human Subjects for International (Non-U.S.) Institutions Original demand one FWA from each non-U.S. trial center Problem >> 100 non-U.S. trial centers

Carrle Office for Human Research Protections (OHRP) Federalwide Assurance (FWA) assurance of compliance with the federal regulations for the Protection of Human Subjects for International (Non-U.S.) Institutions Original demand one FWA from each non-U.S. trial center Problem >> 100 non-U.S. trial centers Solution one FWA per coordinating center (study group)

Carrle EU-Directive 2001/20/EC Implementation of Good Clinical Practice Aim: hamonize + simplify legal requirements for human research

Carrle EU-Directive:Complexity Europe - Fragmentation EU-Directive ≠ Law  Implementation differs among member nations

Carrle EURAMOS in Europe: 12 countries 12 different national interpretations 12ethics committees but 1 sponsor EU-Directive:Complexity Europe - Fragmentation

Carrle Legal responsibility initiation, management and/or funding of the trial in countries with different jurisdiction Sponsor Euramos according to EU-Directive 2001/20 EC

Carrle Delegation of responsibilities Sponsor Euramos according to EU-Directive 2001/20 EC

Carrle Delegation of responsibilities Non-fault insurance Funding Ethics committes regulatory Sponsor Euramos according to EU-Directive 2001/20 EC

Carrle COSS COG EOISSG Common Infrastructure Dataflow

Carrle COSS COG EOISSG Common Infrastructure Dataflow

Carrle Münster Thanks to Matt Sydes - MRC 2008!

Carrle Lobbying Lancet Oncology 2007 OECD-workshop 10.Nov 09 Brussel Can we facilitate Investigator-driven Clinical Trials?

Carrle EURAMOS-CDC, MRC London Recruitment 1574 Patients from 312 Institutions in 15 Countries

Carrle EURAMOS-countries : recruitment Comparison: actual (3.5 years) - potential Potential recruite- ment  730/y

Carrle Recruitment by continent Northamerica+associates vs Europe

Carrle Country-specific recruitment 30.Sept 09 CentersPat.P/C CentersPat. P/C Phenomen: S Bielack

Carrle Recruitment by age: young adults MRC-CDC Cumulative registrations Jul-05 Jul-06 Jul-07 Jul-08 Jul-09 Reg Date <19 years>20 years Cumulative registrations by age Eligibility: Age < 40yrs

Carrle EURAMOS-1 Recruitment by age *Mascarenhas et al 2006

Carrle Recruitment by age: study groups

Carrle Conclusion EURAMOS-1 successful international collaboration  Functioning infrastructure established  Considerable bureaucratic obstacles overcome Excellent recruitment+time-scale  Largest OS trial ever Future: to continue collaboration

Carrle Acknowledgement: EURAMOS-1 Joint effort:Crazy Dreamer Division +Research and Development Dpt

Carrle EURAMOS-1 EURAMOS-Investigator Meeting London 2008 Joint effort:Crazy Dreamer Division +Research and Development Dpt