Current Status of International Clinical Trials in Pediatric

Current Status of International Clinical Trials in Pediatric Cancer: Children’s Oncology Group Gregory H. Reaman Chair Children’s Oncology Group

Pediatric Cancer Drug Development and International Cooperation: Case Statement u Limited patient numbers for early Phase studies u Expanded Phase III study populations u Rare disease types with potential molecular targets u Access to new agents u Communication Global prioritization

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

Barriers (cont. ) u New agents access and distribution u Correlative studies; specimen acquisition and transfer u Funding variances u Regulatory requirements: Inconsistencies, Inflexibility

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

COG International Experiences u NHL: CCG 5961/ LMB u EURO-Ewing’s u Osteosarcoma-EURAMOS

CCG 5961/ LMB u CCG, SFOP, UKCCSG u Opened: May 1996 u Total accrual: 1200 u Individual Group responsibility: v Data collection/ management v Centralized data analysis (outcome) with review v Shared publication responsibility v No FWA requirement outside U. S. /Canada

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

EURAMOS (COG AOST 0331) u International trial: Canada, US, Austria, Belgium, Denmark, Finland, Germany, Great Britain, Ireland, Hungary, The Netherlands, Norway, Sweden, and Switzerland (>200 European centers) Opened 11/2005 u 50% of projected patient accrual non-COG u 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 u EXTERNAL DSMC

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

EURAMOS (cont. ) u COG holds IND for PEG-Intron v Distributed in Europe, Canada, and U. S. by Roche u Accrual ahead of projection u Discussions underway for F/U study

International Participation in COG Clinical Trails u Dutch Childhood Oncology Group (SKION) v (all 7 academic centers)- NHL, CNS, HD studies NHL CNS v Coordinating Center, SKION Headquarters, The Hague u Israel Society of Pediatric Hematology-Oncology v (6 academic centers)- HD, CNS HD v Coordinating Center, Schneider Children’s Hospital, Tikva, Tel Aviv Petah– u Centro Infantil Boldrini, Campinas (Sao Paulo) Brazil and Instituto de Oncologia Pediatrica, Sao Paulo, Brazil v ARAR 0332 – Rx of adrenocortical carcinoma with surgery, LN dissection, and multi-agent chemotherapy

Pending International Trial Participation u JP Garrahan Children’s Hospital: Buenos Aires, Argentina ARET 0321 – Extra-Ocular RB u LV Prasad Eye Institute: Hyderabad, India Sankara Nethralaya, Chennai, India ARET 0231, ARET 0321, ARET 0332 ARET 0231 ARET 0321 ARET 0331 u UKCCLG (MRC Leukemia Working Party) University of Birmingham, Coordinating Center AAML 0561 Phase II study of Lestaurtinib in relapsed AML