EXOme Rare Cancers in Children (EXOCARE)

NCT03472807 | Terminated

• 1 other identifier: 2017-A01833-50
• Study Type: interventional
• Target: 169
• Locations: 2 countries
• Sites: 27

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.

Conditions

Predisposition, Genetic; Cancer Childhood; Development Delay

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Related to secondary objectives (1) : Identification of biological pathways involved in childhood cancer predisposition.

  At inclusion

• Related to secondary objectives (2) : Overall success rate.

  At inclusion

• Related to secondary objectives (3) : Number of clinical criteria justifying a WES.

  At inclusion

Study Arms (2)

Cancer patient

OTHER

* Collection of blood sample or saliva * Collection of a tumor sample taken before the participation of the patient in study * Collection of blood sample if tumor sample is not available

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

Parent of cancer patient

OTHER

-Collection of blood sample or saliva

Other: Collection of blood sample or saliva

Interventions

Collection of blood sample or saliva OTHER

at Inclusion

Cancer patient; Parent of cancer patient

Collection of a tumor sample taken before the participation of the patient in study OTHER

at Inclusion

Cancer patient

Collection of blood sample if tumor sample is not available OTHER

at Inclusion

Cancer patient

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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" :

You may not qualify if:

• 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" :

Sponsors & Collaborators

• University Hospital, Angers: lead

Study Sites (27)

University Hospital of Amiens

Amiens, France

Location

University Hospital of Angers

Angers, France

Location

Cancer Center Bergonie Institut

Bordeaux, France

Location

University Hospital of Bordeaux

Bordeaux, France

Location

University Hospital of Brest

Brest, France

Location

University Hospital of Clermont Ferrand

Clermont-Ferrand, France

Location

University Hospital of Dijon

Dijon, France

Location

University Hospital of Grenoble

Grenoble, France

Location

University Hospital of Lille

Lille, France

Location

University Hospital of Limoges

Limoges, France

Location

Institut of Haematology and Paediatric Oncology of Lyon

Lyon, France

Location

University Hospital of Marseille

Marseille, France

Location

University Hospital of Montpellier

Montpellier, France

Location

University Hospital of Nancy

Nancy, France

Location

University Hospital of Nantes

Nantes, France

Location

University Hospital of Nice

Nice, France

Location

Institut Curie

Paris, France

Location

University Hospital of Kremlin Bicetre

Paris, France

Location

University Hospital of Necker

Paris, France

Location

University Hospital of Trousseau

Paris, France

Location

University Hospital of Rennes

Rennes, France

Location

University Hospital of Rouen

Rouen, France

Location

University Hospital of Saint Etienne

Saint-Etienne, France

Location

University Hospital of Strasbourg

Strasbourg, France

Location

University Hospital of Tours

Tours, France

Location

Institut Gustave Roussy

Villejuif, France

Location

University Hospital of Saint Denis de La Reunion

Saint-Denis, Reunion

Location

MeSH Terms

Conditions

Genetic Predisposition to Disease; Neoplasms; Learning Disabilities

Condition Hierarchy (Ancestors)

Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Neurodevelopmental Disorders; Mental Disorders

Study Officials

• Isabelle PELLIER, Pr

  UH Angers

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: prospective multicenter study, not therapeutic,

Study Record Dates

• First Submitted: January 29, 2018
• First Posted: March 21, 2018
• Study Start: November 13, 2019
• Primary Completion: February 22, 2024
• Study Completion: February 22, 2024
• Last Updated: March 17, 2025

Record last verified: 2025-03

Locations

RE (1); FR (26)