A European Perspective

1
A European Perspective

• Dr Bruce Morland
• Chairman United Kingdom Childrens Cancer Study
  Group (UKCCSG)
• New Agents Committee

2
Challenges

• Access to new drugs alongside not after adult
  Phase I/II development
• New European Legislation Better Medicines for
  Children expected 2004
• Good Clinical Practice (GCP), Good Manufacturing
  Practice (GMP), Doctors and Dentists Exemption
  (DDX) - and likely impact on academic drug
  development programmes

3
United Kingdom Childrens Cancer Study Group
4
UKCCSG

• Founded in 1977
• 22 treatment centres in UK
• 380 members
• 40 overseas members
• UKCCSG Data Centre in Leicester

5
New Agents Group

• Formed in 1987
• Involved in Phase I/II trials
• Relapse Registry
• 1995 established formal link and collaboration
  with SFOP pharmacology group

6
NAG Studies (1)

• NAG 8702
• Phase II carboplatin
• NAG 8801
• mIBG Phase I/II
• NAG 8802
• Etoposide Phase II in relapsed Wilms tumours
• NAG 9007
• GM-CSF prophylaxis post intensive chemo
• NAG 9009
• Monoclonal Targeting NHL/ALL
• NAG 9010
• Monoclonal targeting of medulloblastoma/PNET

7
NAG Studies (2)

• NAG 9012
• Phase I Thiotepa
• NAG 9203
• Oral etoposide Phase II
• NAG 9401
• Phase I Temozolomide
• NAG 9402
• Carboplatin pharmacokinetics
• NAG 9504
• Phase II Thiotepa
• NAG 9509
• Phase I AG337
• NAG 2000 01
• Phase I BU12-SAPORIN immunotoxin

8
UKCCSG Code of Conduct for Clinical Trials

• Finalised June 2000
• Trial development
• Opening a trial
• During the course of a trial
• Closure of a trial
• Publication
• Centre responsibilities
• UKCCSG information/staff training

9
Opening a study

• Initial discussions in NAG
• Concept protocol to UKCCSG meeting
• (Final protocol to UKCCSG meeting)
• MREC submission
• LREC submission
• Open study
• First thought to open study never less than 1
  year often 2 years.

10
UKCCSG Code of ConductPhase I studies

• Commitments
• Documentation
• GCP
• SAEs (24hrs)
• Monitoring
• Staffing
• Lead clinician
• Research Nurse
• Pharmacist
• Facilities
• Drug supply
• PK studies
• Data storage

11
UKCCSG Code of ConductPhase II studies

• Commitments
• SAE reporting (not necessarily 24hr)
• Staffing
• Data manager or research nurse

12
The NAG/SFOP collaboration
13
Joint studies

• Phase II Temozolomide
• PSC833 Phase I
• DaunoXome Phase I
• CPT11 Phase II

14
Development of CPT-11 in Paediatric Oncology in
Europe
1990
1992
1994
1996
1998
2000
2002
ADULTS
Phase I
F
E
Approval
Phase II
Children
The facts
7 years
The goal
18 months
15
European New Drug Developmentrecent achievements

• Since 1995 8 phase I, 6 phase II, 1 PK
  (completed)4 phase I, 2 phase II, 7 PK (ongoing
  or ready)gt500 patients
• 11 new drugsall started after approval for adults

NAG and GP-SFOP
16
The ITCC Project

• An Integrated Pan European Clinical Research
  Networkto design and conducta comprehensive
  drug development programme in pediatric cancers

17
The ITCC Project

• Core Group
• IGR
• CR-UK
• NAG UKCCSG
• GP-SFOP
• NL-NAG
• Westfalische Wilhelms Universitat, Münster
• PG- AIEOP
• University of Newcasttle

18
Academia
Pharma
CRUK
ITCC
UKCCSG SFOP etc.
Regulatory Authorities
Treating institutions
19
Development of CPT-11 in Paediatric Oncology in
Europe
1990
1992
1994
1996
1998
2000
2002
ADULTS
Phase I
F
E
Approval
Phase II
Children
The facts
7 years
The goal
18 months