Proof -of -Concept Study To Stratify Targeted Therapies Adapted To Molecular Profiling
- Conditions
- Relapsed or Refractory Pediatric Tumor
- Interventions
- Procedure: biopsy or surgical resection of tumor and blood sampling
- Registration Number
- NCT02613962
- Lead Sponsor
- Gustave Roussy, Cancer Campus, Grand Paris
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 700
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description relapsed or refractory pediatric tumor biopsy or surgical resection of tumor and blood sampling This is a prospective, international, multicentric clinical proof-of-concept study to stratify targeted therapies adapted to molecular profiling of relapsed or refractory pediatric tumors. The molecular screening will be done on a newly biopsied or resected tumor sample obtained at the time of relapse/progression, using high-throughput technologies, primarily WES and RNA Sequencing, and bioinformatics analysis.
- Primary Outcome Measures
Name Time Method The percentage of patients with recurrent or refractory pediatric solid tumor or leukemia that could be attributed to treatment with matched targeted agents assessed four years after beginning of study The percentage of patients with recurrent or refractory pediatric solid tumor or leukemia that could be attributed to treatment with matched targeted agents according to the molecular profile in their individual tumor will be estimated
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (5)
Gustave Roussy
🇫🇷Villejuif, Val De Marne, France
Hospital Universitari Vall D'Hebron
🇪🇸Barcelona, Cataluna, Spain
Fondazione IRCCS Istituto
🇮🇹Milano, Italy
Our Lady's Children's Hospital
🇮🇪Dublin, Crumlin, Ireland
Schneider Children's Medical Center
🇮🇱Petach Tikva, Israel