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Carrle 2009.11.06
The European and American Osteosarcoma Study
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-2003-980409 of the European Commission DG Research FP6
Carrle 2009.11.06
EURAMOS-1: Study objectives
2 Focuses: Scientific: Improve treatment results: •Poor responder:
Salvage therapy (+/- HD-Ifo/Eto)•Good reponder:
Maintenance therapy (+/- Peg-Interferon)
Carrle 2009.11.06
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 2009.11.06
DisclaimerThis presentation is not about survival data of EURAMOS-1
but about other relevant outcome from a large multinational clinical trial
Carrle 2009.11.06
Osteosarcoma: 5-Year Survival
Osteosarcoma: Internat study results
Stiller et al EJC 2006
Mirabello et al Cancer 2009
Carrle 2009.11.06
Osteosarcoma: 5-Year Survival
•Survival plateau
Osteosarcoma: Internat study results
Stiller et al EJC 2006
Mirabello et al Cancer 2009
Carrle 2009.11.06
Osteosarcoma: 5-Year Survival
•Survival plateau
•Slow Progress
Osteosarcoma: Internat study results
Stiller et al EJC 2006
Mirabello et al Cancer 2009
Carrle 2009.11.06
Osteosarcoma: 5-Year Survival
•Survival plateau
•Slow Progress
•Salvage-question unresolved
Osteosarcoma: Internat study results
Stiller et al EJC 2006
Mirabello et al Cancer 2009
Carrle 2009.11.06
Osteosarcoma: 5-Year Survival
•Survival plateau
•Slow Progress
•Salvage-question unresolved
Osteosarcoma: Internat study results
Stiller et al EJC 2006
Mirabello et al Cancer 2009
Carrle 2009.11.06
Osteosarcoma: 5-Year Survival
•Survival plateau
•Slow Progress
•Salvage-question700 poor responders2000 patients
Osteosarcoma: Internat study results
Stiller et al EJC 2006
Mirabello et al Cancer 2009
Carrle 2009.11.06
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 2009.11.06
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 2009.11.06
EURAMOS-countries: Potential recruitment
583 Mio= 8.7% of world
population
Osteosarkom-Inc.≈2-3 per Mio/Year
≈50% eligible
730/year
Carrle 2009.11.06
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 2009.11.06
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 2009Hawkins D J Ped Hem
2004
Carrle 2009.11.06
EURAMOS-group 1st. MeetingBrisbane 2001
Carrle 2009.11.06
EURAMOS-group 1st. MeetingBrisbane 2001
Research and Development Department
Carrle 2009.11.06
Research and Development Department Crazy Dreamer
Division
EURAMOS-group 1st. MeetingBrisbane 2001
Carrle 2009.11.06
SSG
COG
EOI
COSS
EURAMOS: Pan-European/American Collaboration
4 studygroups -15 countries -
Carrle 2009.11.06
Office for Human Research Protections (OHRP)
Federalwide Assurance (FWA)assurance of compliance with the federal regulations for the Protection of Human Subjectsfor International (Non-U.S.) Institutions
Original demandone FWA from each non-U.S. trial center
Problem>> 100 non-U.S. trial centers
Carrle 2009.11.06
Office for Human Research Protections (OHRP)
Federalwide Assurance (FWA)assurance of compliance with the federal regulations for the Protection of Human Subjectsfor International (Non-U.S.) Institutions
Original demandone FWA from each non-U.S. trial center
Problem>> 100 non-U.S. trial centers
Solutionone FWA per coordinating center (study group)
Carrle 2009.11.06
EU-Directive 2001/20/EC
Implementation of Good Clinical PracticeAim: hamonize + simplify legal requirements for human research
Carrle 2009.11.06
EU-Directive:ComplexityEurope - Fragmentation
EU-Directive ≠ LawImplementation
differs among member
nations
Carrle 2009.11.06
EURAMOS in Europe:
12 countries 12 different
national interpretations
12 ethics committees
but 1 sponsor
EU-Directive:ComplexityEurope - Fragmentation
Carrle 2009.11.06
Supported by the European Science Foundation (ESF) under the EUROCORES Program European Clinical Trials (ECT) and managed by the European Medical Research Councils Unit (EMRC) under through contract No. ERASCT-2003-980409 of the European Commission, DG Research, FP6
Collaborations in rare diseases Matt Sydes ( J an - 2008)
EURAMOS groups + structure
C hildren ’s Onco lo gy G rou p (CO G )
US A & Canada
S candinavian S arcom a G roup ( SSG )
D enm ark, Fin land, I ce land, N orway, S w eden
Quality o f L ife Centre: Düsseldorf
G erm any
I ntergrou p S afety D esk: K K S Münster
G erm any
Coordin ating Data Cen tre : MRC C lin ica l Tr ia ls Un it, UK
Cooperative Osteosarcom a S tudy G roup ( CO SS )
A ustria , Germ any, H ungary, S w itzer land
European Osteosarcom a I n tergrou p ( EO I )
Belg ium , N etherlands , U K
US A
CanadaS w itzer land
Hungary
Austria
G erm any
Nether lands
Belg ium
UK I celand
D enm ark
F in land
N orway
S weden
EUR AMO S Central Accoun t
Sch ering Plough ( USA)
Scherin g P lou gh ( EU)
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 2009.11.06
Supported by the European Science Foundation (ESF) under the EUROCORES Program European Clinical Trials (ECT) and managed by the European Medical Research Councils Unit (EMRC) under through contract No. ERASCT-2003-980409 of the European Commission, DG Research, FP6
Collaborations in rare diseases Matt Sydes ( J an - 2008)
EURAMOS groups + structure
C hildren ’s Onco lo gy G rou p (CO G )
US A & Canada
S candinavian S arcom a G roup ( SSG )
D enm ark, Fin land, I ce land, N orway, S w eden
Quality o f L ife Centre: Düsseldorf
G erm any
I ntergrou p S afety D esk: K K S Münster
G erm any
Coordin ating Data Cen tre : MRC C lin ica l Tr ia ls Un it, UK
Cooperative Osteosarcom a S tudy G roup ( CO SS )
A ustria , Germ any, H ungary, S w itzer land
European Osteosarcom a I n tergrou p ( EO I )
Belg ium , N etherlands , U K
US A
CanadaS w itzer land
Hungary
Austria
G erm any
Nether lands
Belg ium
UK I celand
D enm ark
F in land
N orway
S weden
EUR AMO S Central Accoun t
Sch ering Plough ( USA)
Scherin g P lou gh ( EU)
Delegation of responsibilities
Sponsor Euramos according to EU-Directive 2001/20 EC
Carrle 2009.11.06
Supported by the European Science Foundation (ESF) under the EUROCORES Program European Clinical Trials (ECT) and managed by the European Medical Research Councils Unit (EMRC) under through contract No. ERASCT-2003-980409 of the European Commission, DG Research, FP6
Collaborations in rare diseases Matt Sydes ( J an - 2008)
EURAMOS groups + structure
C hildren ’s Onco lo gy G rou p (CO G )
US A & Canada
S candinavian S arcom a G roup ( SSG )
D enm ark, Fin land, I ce land, N orway, S w eden
Quality o f L ife Centre: Düsseldorf
G erm any
I ntergrou p S afety D esk: K K S Münster
G erm any
Coordin ating Data Cen tre : MRC C lin ica l Tr ia ls Un it, UK
Cooperative Osteosarcom a S tudy G roup ( CO SS )
A ustria , Germ any, H ungary, S w itzer land
European Osteosarcom a I n tergrou p ( EO I )
Belg ium , N etherlands , U K
US A
CanadaS w itzer land
Hungary
Austria
G erm any
Nether lands
Belg ium
UK I celand
D enm ark
F in land
N orway
S weden
EUR AMO S Central Accoun t
Sch ering Plough ( USA)
Scherin g P lou gh ( EU)
Delegation of responsibilities
Non-fault insurance
Funding
Ethics committes
regulatory
Sponsor Euramos according to EU-Directive 2001/20 EC
Carrle 2009.11.06
COSS COG EOI SSG
E UROPEANO STEOSARCOMAI NTERGROUP
Common InfrastructureDataflow
Carrle 2009.11.06
COSS COG EOI SSG
E UROPEANO STEOSARCOMAI NTERGROUP
Supported by the European Science Foundation (ESF) under the EUROCORES Program European Clinical Trials (ECT) and managed by the European Medical Research Councils Unit (EMRC) under through contract No. ERASCT-2003-980409 of the European Commission, DG Research, FP6
Collaborations in rare diseases Matt Sydes ( J an - 2008)
EURAMOS groups + structure
C hildren ’s Onco lo gy G rou p (CO G )
US A & Canada
S candinavian S arcom a G roup ( SSG )
D enm ark, Fin land, I ce land, N orway, S w eden
Quality o f L ife Centre: Düsseldorf
G erm any
I ntergrou p S afety D esk: K K S Münster
G erm any
Coordin ating Data Cen tre : MRC C lin ica l Tr ia ls Un it, UK
Cooperative Osteosarcom a S tudy G roup ( CO SS )
A ustria , Germ any, H ungary, S w itzer land
European Osteosarcom a I n tergrou p ( EO I )
Belg ium , N etherlands , U K
US A
CanadaS w itzer land
Hungary
Austria
G erm any
Nether lands
Belg ium
UK I celand
D enm ark
F in land
N orway
S weden
EUR AMO S Central Accoun t
Sch ering Plough ( USA)
Scherin g P lou gh ( EU)
Common InfrastructureDataflow
Carrle 2009.11.06
C o l l a b o r a t i o n s i n r a r e d i s e a s e s M a t t S y d e s ( J a n - 2 0 0 8 )
E U R A M O S g r o u p s + s t r u c t u r e
C h i l d r e n ’ s O n c o l o g y G r o u p ( C O G )
U S A & C a n a d a
S c a n d i n a v i a n S a r c o m a G r o u p ( S S G )
D e n m a r k , F i n l a n d , I c e l a n d , N o r w a y , S w e d e n
Q u a l i t y o f L i f e C e n t r e : D ü s s e l d o r f
G e r m a n y
I n t e r g r o u p S a f e t y D e s k : K K S M ü n s t e r
G e r m a n y
C o o r d i n a t i n g D a t a C e n t r e : M R C C l i n i c a l T r i a l s U n i t , U K
C o o p e r a t i v e O s t e o s a r c o m a S t u d y G r o u p ( C O S S )
A u s t r i a , G e r m a n y , H u n g a r y , S w i t z e r l a n d
E u r o p e a n O s t e o s a r c o m a I n t e r g r o u p ( E O I )
B e l g i u m , N e t h e r l a n d s , U K
U S A
C a n a d aS w i t z e r l a n d
H u n g a r y
A u s t r i a
G e r m a n y
N e t h e r l a n d s
B e l g i u m
U K I c e l a n d
D e n m a r k
F i n l a n d
N o r w a y
S w e d e n
E U R A M O S C e n t r a l A c c o u n t
S c h e r i n g P l o u g h ( U S A )
S c h e r i n g P l o u g h ( E U )
Supported by the European Science Foundation (ESF) under the EUROCORES Program European Clinical Trials (ECT) and managed by the European Medical Research Councils Unit (EMRC) under through contract No. ERASCT-2003-980409 of the European Commission, DG Research, FP6
Collaborations in rare diseases Matt Sydes ( J an - 2008)
EURAMOS groups + structure
Children’s Oncology G rou p (COG )
US A & Canada
S candinavian S arcom a G roup (SSG )
D enm ark, Fin land, I ce land, Norway, S weden
Quality of L ife Centre: Düsseldorf
G erm any
I ntergrou p S afety D esk: K K S Münster
G erm any
Coordinating Data Centre : MRC Clin ica l Tr ia ls Un it, UK
Cooperative Osteosarcom a S tudy G roup ( CO SS )
A ustria , Germ any, Hungary, S w itzer land
European Osteosarcom a I ntergrou p ( EO I )
Belg ium , Netherlands , UK
US A
CanadaS witzer land
Hungary
Austria
G erm any
Nether lands
Belg ium
UK I celand
D enm ark
F in land
Norway
S weden
EURAMO S Central Account
Schering Plough ( USA)
Schering P lough ( EU)
E UROPEANO STEOSARCOMAI NTERGROUP
Münster
Thanks to Matt Sydes - MRC 2008!
Carrle 2009.11.06
LobbyingLancet Oncology 2007
OECD-workshop 10.Nov 09 BrusselCan we facilitate Investigator-driven Clinical Trials?
Carrle 2009.11.06
EURAMOS-CDC, MRC London
Recruitment
1574 Patients
from 312 Institutions
in 15 Countries
Carrle 2009.11.06
EURAMOS-countries: recruitment Comparison: actual (3.5 years) -
potential
Potential
recruite-ment
730/y
Carrle 2009.11.06
Recruitment by continent Northamerica+associates vs
Europe
0
200
400
600
800
Cu
mu
lativ
e re
gist
ratio
ns
Jul-
05
Jul-
06
Jul-
07
Jul-
08
Jul-
09
Reg Date
COG COSS, EOI, SSG
Cumulative registrations by group
Carrle 2009.11.06
Country-specific recruitment 30.Sept
09Centers Pat. P/C
147 701 4.876 324 4.325 215 8.626 71 17.814 61 4.46 33 5.56 30 5.0
Centers Pat. P/C
8 29 3.63 27 9.06 19 3.22 19 9.52 15 7.55 12 2.53 8 2.71 3 3.0-Phenomen: S
Bielack
Carrle 2009.11.06
Recruitment by age: young adults
MRC-CDC 30.09.09
0
500
1000
1500
Cu
mu
lativ
e r
egi
stra
tion
s
Jul-0
5
Jul-0
6
Jul-0
7
Jul-0
8
Jul-0
9
Reg Date
<19 years >20 years
Cumulative registrations by ageEligibilit
y:Age
< 40yrs
Carrle 2009.11.06
EURAMOS-1Recruitment by age
*Mascarenhas et al 2006
Carrle 2009.11.06
Recruitment by age: study groups
Carrle 2009.11.06
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 2009.11.06
Acknowledgement:EURAMOS-1
Joint effort: Crazy Dreamer Division+Research and Development
Dpt
Carrle 2009.11.06
EURAMOS-1
EURAMOS-Investigator MeetingLondon 2008
Joint effort: Crazy Dreamer Division+Research and Development
Dpt