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

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DisclaimerThis presentation is not about survival data of EURAMOS-1

but about other relevant outcome from a large multinational clinical trial

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Osteosarcoma: 5-Year Survival

Osteosarcoma: Internat study results

Stiller et al EJC 2006

Mirabello et al Cancer 2009

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Osteosarcoma: 5-Year Survival

•Survival plateau

Osteosarcoma: Internat study results

Stiller et al EJC 2006

Mirabello et al Cancer 2009

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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

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EURAMOS-group 1st. MeetingBrisbane 2001

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EURAMOS-group 1st. MeetingBrisbane 2001

Research and Development Department

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Research and Development Department Crazy Dreamer

Division

EURAMOS-group 1st. MeetingBrisbane 2001

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SSG

COG

EOI

COSS

EURAMOS: Pan-European/American Collaboration

4 studygroups -15 countries -

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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

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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)

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EU-Directive 2001/20/EC

Implementation of Good Clinical PracticeAim: hamonize + simplify legal requirements for human research

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EU-Directive:ComplexityEurope - Fragmentation

EU-Directive ≠ LawImplementation

differs among member

nations

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EURAMOS in Europe:

12 countries 12 different

national interpretations

12 ethics committees

but 1 sponsor

EU-Directive:ComplexityEurope - Fragmentation

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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

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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

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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

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COSS COG EOI SSG

E UROPEANO STEOSARCOMAI NTERGROUP

Common InfrastructureDataflow

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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

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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!

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LobbyingLancet Oncology 2007

OECD-workshop 10.Nov 09 BrusselCan we facilitate Investigator-driven Clinical Trials?

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EURAMOS-CDC, MRC London

Recruitment

1574 Patients

from 312 Institutions

in 15 Countries

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EURAMOS-countries: recruitment Comparison: actual (3.5 years) -

potential

Potential

recruite-ment

730/y

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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

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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

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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

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EURAMOS-1Recruitment by age

*Mascarenhas et al 2006

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Recruitment by age: study groups

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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

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Acknowledgement:EURAMOS-1

Joint effort: Crazy Dreamer Division+Research and Development

Dpt

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EURAMOS-1

EURAMOS-Investigator MeetingLondon 2008

Joint effort: Crazy Dreamer Division+Research and Development

Dpt