Relapsed or Refractory Pediatric Tumor Clinical Trial
Official title:
A Prospective, Multicentric Clinical Proof-of-concept Study to Stratify Targeted Therapies Adapted to Molecular Profiling of Relapsed or Refractory Pediatric Tumors
In the light of the development of high-throughput technologies enabling a biology-based
reclassification of tumors and the increasing number of available specifically targeting
anticancer agents the era of "precision medicine" has begun. Several clinical precision
medicine trials with the aim of stratifying treatment according to molecular profiles (for
example in France: 'MOlecular Screening for CAncer Treatment Optimization' MOSCATO-01, SHIVA,
PROFILER, Safir01, Safir02) are ongoing in adults and have shown the feasibility of this
approach. MOSCATO-01 is the first trial worldwide including pediatric patients, performing an
on-purpose intervention and molecular profiling in recurrent tumors. Together with more than
500 adult patients, between December 2012 to August 2014, the tumors of 35 children and
adolescents have been profiled, confirming that this approach is feasible in pediatric
patients albeit with accelerated time stringencies. Importantly, the results of the first
children and adolescents profiled showed that 2/3 of patients had 'actionable' alterations
using hot spot mutations sequencing and CGH array (Geoerger B et al, ASCO 2014).
The project 'MAPPYACTS' will use both Whole Exome Sequencing (WES) and RNA Sequencing of
tumor tissue to increase the number of targetable genomic alterations. Furthermore to improve
understanding of the overall molecular profile and possible response to treatment,
methylation array, miRNA expression profiles, and study of immunomodulators will be performed
on tumor samples subsequently. CLIP2 (INCa-labeled early phase clinical trials centers) -
SiRIC (INCa- labeled comprehensive cancer centers) molecular profiling and bioinformatics
platforms will contribute with their expertise in molecular profiling projects and
characterization of pediatric cancers. Data interpretation of molecular genetic alterations
detected by WES and RNA Seq and treatment recommendation will be done within a
multidisciplinary therapeutic molecular biology tumor board.
'MAPPYACTS' will produce one of the largest cohorts of molecularly characterized relapsed
tumors reported to date, and thanks to increased access to clinical trials since the European
pediatric legislation, the investigators expect that 20-30% of patients can be stratified
into a targeted trial based on the detected profile.
It is the investigators' intention that this initiative paves the way to enrich ongoing
clinical targeted agent trials, to increase the numbers of stratified clinical trials, to an
earlier access to targeted agents, and will play a crucial role in the relevant development
of these new agents in pediatric malignancies.
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