EXOme Rare Cancers in Children (EXOCARE)

Development Delay Clinical Trial

— EXOCARE  

Official title:

An Investigation of Susceptibility Genes for Rare Cancers in Children by Exome Sequencing

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03472807
• Other study ID #: 2017-A01833-50
• Status: Recruiting
• Phase: N/A
• Start date: November 13, 2019
• Est. completion date: August 13, 2025

Study information

• Verified date: November 2023
• Source: University Hospital, Angers
• Contact: Elsa BERARDI
• Phone: +33 2 41 35 61 79
• Email: elberardi[@]chu-angers.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: August 13, 2025
• Est. primary completion date: February 13, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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"

Related Conditions & MeSH terms

• Cancer Childhood
• Development Delay
• Genetic Predisposition to Disease
• Predisposition, Genetic

Intervention

Other:
• Collection of blood sample or saliva
at Inclusion
• Collection of a tumor sample taken before the participation of the patient in study
at Inclusion
• Collection of blood sample if tumor sample is not available
at Inclusion

Locations

Country	Name	City	State
France	University Hospital of Amiens	Amiens
France	University Hospital of Angers	Angers
France	Cancer Center Bergonie Institut	Bordeaux
France	University Hospital of Bordeaux	Bordeaux
France	University Hospital of Brest	Brest
France	University Hospital of Clermont Ferrand	Clermont-Ferrand
France	University Hospital of Dijon	Dijon
France	University Hospital of Grenoble	Grenoble
France	University Hospital of Lille	Lille
France	University Hospital of Limoges	Limoges
France	Institut of Haematology and Paediatric Oncology of Lyon	Lyon
France	University Hospital of Marseille	Marseille
France	University Hospital of Montpellier	Montpellier
France	University Hospital of Nancy	Nancy
France	University Hospital of Nantes	Nantes
France	University Hospital of Nice	Nice
France	Institut Curie	Paris
France	University Hospital of Kremlin Bicetre	Paris
France	University Hospital of Necker	Paris
France	University Hospital of Trousseau	Paris
France	University Hospital of Rennes	Rennes
France	University Hospital of Rouen	Rouen
France	University Hospital of Saint Etienne	Saint-Étienne
France	University Hospital of Strasbourg	Strasbourg
France	University Hospital of Tours	Tours
France	Institut Gustave Roussy	Villejuif
Réunion	University Hospital of Saint Denis de La Reunion	Saint-Denis

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Angers

Countries where clinical trial is conducted

France,  Réunion, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number and type of germline and somatic genetic variants of pathological significance and associated with the disease.	WES and RNA sequence data will be used to identify and characterise germline and somatic genetic variants of pathological significance and associated with the disease.; Descriptive statistics, such as counts and proportions of variants of pathological significance risk will be computed within each patient and family.	At inclusion
Secondary	Related to secondary objectives (1) : Identification of biological pathways involved in childhood cancer predisposition.	The deleterious mutations that the investigators will identify in genes related to childhood cancer predisposition will help to have a comprehensive framework of biological pathways involved in childhood cancer predisposition.	At inclusion
Secondary	Related to secondary objectives (2) : Overall success rate.	Success is defined by the combined successes of quality interpretable genomic data are generated from sequencing tumor and germline tissues, and communicating genomic test results to the primary oncologist and the patient and his/her parents.	At inclusion
Secondary	Related to secondary objectives (3) : Number of clinical criteria justifying a WES.	Descriptive statistics, such as counts and proportions of success by clinical presentation of the disease, by cancer types, by features of developmental delay, and, by class of age.	At inclusion