# Presentation: 914963

## 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

**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**

## 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**

## Barriers (cont.)

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

## 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)**

## COG International Experiences

**NHL: CCG 5961/ LMB**
**EURO-Ewing’s**
**Osteosarcoma-EURAMOS**

## 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**

## 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**

## EURAMOS(COG AOST0331)

**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**
**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 **

## 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**

## 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**

## 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 Children’s Hospital,    Petah–Tikva, 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 **

## Pending International Trial Participation

**JP Garrahan Children’s 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**