Innovative Therapies for Children with Cancer in Europe

  • Innovative Therapies
    for Children with Cancer in Europe
  • Contact us

Innovative Methodology:

The main objective of any phase I clinical trials is to identify the optimal dose and to establish the toxicity profile of the new compound under study. The compounds under study in children raise challenging issues due to both the rarity of paediatric cancers and the specificities of innovative drugs:

  • Some compounds are believed to work at the maximal tolerated dose (e.g. cytotoxic compounds); others are believed to work at a optimal biological dose (e.g. Glivec® active at non toxic doses or Tarceva® ). Thus, endpoints and trial designs to define the optimal dose are probably different.
  • The number of pediatric patients eligible for early drug development is small. These studies need to be multicentre at a national, European or international level.
  • A paediatric phase I trial is started only after phase I studies have been undertaken in adult cancer patients, which allows the anticipation of most of toxicity in children. Currently this information is used only when determining the lowest initial dose for pediatric phase I studies (usually chosen as 80% of the recommended dose in adults but much more should be exploited).
  • Heterogeneity of paediatric populations (due to age, disease status, previous-treatments) makes it difficult to identify one universal optimal dose. It would be of interest to incorporate covariates into the trial design so that optimal doses can be identified for different sub-groups.
  • Original methodologies and designs are needed to minimise the number of patients required, and to optimise exposure of all eligible patients to potentially active drug. The goal is to design and validate new methodologies for the evaluation of new drugs in children with cancer which can be used within the ITCC consortium over the next 10 years. The development of new designs of studies is a joint program in Curie and IGR, funded by the French National Cancer Institute. Several researchers are already working to study:
  • Intra-patient escalation design for early stage trials of chronic treatments
  • Identification of group-specific optimal doses
  • Combining toxicity and efficacy in early cancer trials of targeted therapy