Clinical trial NCT03472807: EXOme Rare Cancers in Children (EXOCARE)
Official title: An Investigation of Susceptibility Genes for Rare Cancers in Children by Exome Sequencing
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Predisposition, Genetic
Cancer Childhood
Development Delay
Lead sponsor: University Hospital, Angers
Sponsor class: OTHER_GOV
First posted: 2018-03-21
Enrollment: 169
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: prospective multicenter study, not therapeutic,
Primary purpose: DIAGNOSTIC

Brief summary: Other than high-dose radiation and previous chemotherapy, few strong risk factors have been identified as causes of childhood cancer. Geneticists estimate that 5 to 10% of all cancers diagnosed during the paediatric period occur in children born with a genetic mutation, increasing their lifetime risk of neoplasia. Such genetic risk is higher in children with congenital anomalies and specific genetic syndromes. Some germline genetic alterations are well known (e.g. P53 protein (P53), Neurofibromatosis type 1(NF1)), however many children with none of these mutations have clinical presentations that strongly suggest the involvement of a genetic predisposition. Comprehensive genetic testing for all such patients is an important factor for improving disease surveillance. Such opportunities are now available thanks to whole exome sequencing (WES). In oncology, an important clinical application of WES will be to routinely identify mutations associated with inherited cancer predispositions and to guide cancer risk-management decisions.

Our project is a national translational multicenter genetics study aimed at identifying genes involved in paediatric cancer predisposition by WES in a very select population of children with both developmental delay and cancer. Our project relies on the TED register (Tumeur Et Développement), an initiative by the French organisation SFCE (Société Française de lutte contre les Cancers et les leucémies de l'Enfant et de l'Adolescent) involving 30 child cancer units in France. This database includes the information of more than 500 paediatric cancer patients with congenital abnormalities. The investigators plan to sequence the germline and tumour exome of 100 patients with developmental delay in a trio-design consisting of 300 people and 100 tumours.

The investigators believe that the ExoCaRe project will provide answers to the genetic origins of certain particular childhood cancers. The ExoCaRe project relies on a genetic study to identify genetic risk factors for rare forms of childhood cancer and aims to establish more personalised treatment. It is aimed at improving genetic counselling for families and will be fully integrated in the genetic counselling process. The information provided by our study will be used to improve the management approach to an initial cancer by clarifying the risks of other cancers in related families. The investigators hope to identify new germline genes predisposing to cancer that will be of interest in understanding tumour biology.

Detailed description: -Primary objective : Our aim is to identify new mutations and genes involved in paediatric cancer predisposition associating developmental delay by WES of a sub-cohort of patients included in the TED database.

-Secondary objectives :

1. Describe inherited predisposition to cancer.
2. Improve genetic counselling processes.
3. Initiate clinical exome sequencing in childhood cancer treatment.

Eligibility criteria: Inclusion Criteria:

* For "Patient cancer" :

  * Child having developed a cancer combined with a delay of development and\\or an intellectual deficiency before the age of 18 years and followed for a cancer of the child in one of hospital center of the Société Française de lutte contre les Cancers et les leucémies de l'Enfant et de l'adolescent (SFCE)
  * At least a parent still alive and available to make genetic analyses
* For "Parent of cancer patient" :

  * Parent whose child meets the criteria of inclusion of "Cancer patient"

Exclusion Criteria:

* For "Cancer patient" :

  * Genetic predisposition already identified at the child
  * Absence of histological confirmation
  * Child died without DNA of the available germinal lineage
* For "Parent of cancer patient" :

  * Parent whose child doesn't meets the criteria of inclusion of "Cancer patient"

Primary outcomes:
measure: Number and type of germline and somatic genetic variants of pathological significance and associated with the disease.
timeFrame: At inclusion
Secondary outcomes:
measure: Related to secondary objectives (1) : Identification of biological pathways involved in childhood cancer predisposition.
timeFrame: At inclusion
measure: Related to secondary objectives (2) : Overall success rate.
timeFrame: At inclusion
measure: Related to secondary objectives (3) : Number of clinical criteria justifying a WES.
timeFrame: At inclusion
Other outcomes:
Locations:
city: Amiens
country: France
facility: University Hospital of Amiens
city: Angers
country: France
facility: University Hospital of Angers
city: Bordeaux
country: France
facility: Cancer Center Bergonie Institut
city: Bordeaux
country: France
facility: University Hospital of Bordeaux
city: Brest
country: France
facility: University Hospital of Brest
city: Clermont-Ferrand
country: France
facility: University Hospital of Clermont Ferrand
city: Dijon
country: France
facility: University Hospital of Dijon
city: Grenoble
country: France
facility: University Hospital of Grenoble
city: Lille
country: France
facility: University Hospital of Lille
city: Limoges
country: France
facility: University Hospital of Limoges
city: Lyon
country: France
facility: Institut of Haematology and Paediatric Oncology of Lyon
city: Marseille
country: France
facility: University Hospital of Marseille
city: Montpellier
country: France
facility: University Hospital of Montpellier
city: Nancy
country: France
facility: University Hospital of Nancy
city: Nantes
country: France
facility: University Hospital of Nantes
city: Nice
country: France
facility: University Hospital of Nice
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: University Hospital of Kremlin Bicetre
city: Paris
country: France
facility: University Hospital of Necker
city: Paris
country: France
facility: University Hospital of Trousseau
city: Rennes
country: France
facility: University Hospital of Rennes
city: Rouen
country: France
facility: University Hospital of Rouen
city: Saint-Étienne
country: France
facility: University Hospital of Saint Etienne
city: Strasbourg
country: France
facility: University Hospital of Strasbourg
city: Tours
country: France
facility: University Hospital of Tours
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Saint-Denis
country: Réunion
facility: University Hospital of Saint Denis de La Reunion
Study officials:
affiliation: UH Angers
name: Isabelle PELLIER, Pr
role: PRINCIPAL_INVESTIGATOR
References: