Current Status of International Clinical Trials in Pediatric Cancer: Children

1
Current Status of International Clinical Trials
in Pediatric CancerChildrens Oncology Group

• Gregory H. Reaman
• Chair
• Childrens Oncology Group

2
Pediatric Cancer Drug Development and
International Cooperation Case Statement

• Limited patient numbers for early Phase studies
• Expanded Phase III study populations
• Rare disease types with potential molecular
  targets
• Access to new agents
• Communication Global prioritization

3
Perceived (Historical) Barriers

• Cultural and health care delivery differences
• Participation, collaboration, (design),
  coordination
• Compliance with GCP guidelines and assurance
• Conduct Institutional, Consortium, Group
  collaboration
• Informatics data capture, electronic platforms,
  language, data management/ analysis/ reporting

4
Barriers (cont.)

• New agents access and distribution
• Correlative studies specimen acquisition and
  transfer
• Funding variances
• Regulatory requirements Inconsistencies,
  Inflexibility

5
COG and International Collaboration

• Although U.S. based and NCI-supported strong
  international representation
• 17 study sites in Canada (SMO for Canadian
  Affairs)
• 8 study sites in Australia
• 3 study sites in New Zealand
• 3 study sites in Switzerland
• 2 study sites in The Netherlands
• 2 study sites in Mexico (planning)

6
COG International Experiences

• NHL CCG 5961/ LMB
• EURO-Ewings
• Osteosarcoma-EURAMOS

7
CCG 5961/ LMB

• CCG, SFOP, UKCCSG
• Opened May 1996
• Total accrual 1200
• Individual Group responsibility
• Data collection/ management
• Centralized data analysis (outcome) with review
• Shared publication responsibility
• No FWA requirement outside U.S./Canada

8
EURO-Ewing's

• CTEP approved COG participation in existing trial
  (metastatic patients only)
• Randomization (Intensive chemo. vs. high dose
  therapy and stem cell rescue)
• Non-U.S. coordination
• FWA required for coordinating center only
  University of Muenster

9
EURAMOS(COG AOST0331)

• International trial Canada, US, Austria,
  Belgium, Denmark, Finland, Germany, Great
  Britain, Ireland, Hungary, The Netherlands,
  Norway, Sweden, and Switzerland (gt200 European
  centers) Opened 11/2005
• 50 of projected patient accrual non-COG
• European institutions committed to comply with
  Directive 2001/20/EC of The European Parliament
  and of the Council, 4/04/01 and ICH-GCP standards
• EXTERNAL DSMC

10
EURAMOS (cont.)

• Relevant European and American laws ensure human
  research subject protection (ICH-GCP standards)
  including independent ethics board approval
• Equal partners no right for single group
  (country) to impose local regulations
• Sufficient safeguards Adherence to Declaration
  of Helsinki and compliance with ICH-GCP
• FWA requirement all participating European
  institutions vs. coordinating center
• Acceptable Quality Assurance mechanism

11
EURAMOS (cont.)

• COG holds IND for PEG-Intron
• Distributed in Europe, Canada, and U.S. by Roche
• Accrual ahead of projection
• Discussions underway for F/U study

12
International Participation in COG Clinical
Trails

• Dutch Childhood Oncology Group (SKION)
• (all 7 academic centers)- NHL, CNS, HD studies
• Coordinating Center, SKION Headquarters, The
  Hague
• Israel Society of Pediatric Hematology-Oncology
• (6 academic centers)- HD, CNS
• Coordinating Center, Schneider Childrens
  Hospital, PetahTikva, Tel Aviv
• Centro Infantil Boldrini, Campinas (Sao Paulo)
  Brazil and Instituto de Oncologia Pediatrica, Sao
  Paulo, Brazil
• ARAR0332 Rx of adrenocortical carcinoma with
  surgery, LN dissection, and multi-agent
  chemotherapy

13
Pending International Trial Participation

• JP Garrahan Childrens Hospital Buenos Aires,
  Argentina
• ARET0321 Extra-Ocular RB
• LV Prasad Eye Institute Hyderabad, India
• Sankara Nethralaya, Chennai, India
• ARET0231, ARET0321, ARET0331, ARET0332
• UKCCLG (MRC Leukemia Working Party)
• University of Birmingham, Coordinating Center
• AAML0561 Phase II study of Lestaurtinib in
• relapsed AML