Description of Individual Radiosensitivity With Molecular Biomarkers in a Pediatric Oncology Population

Cancer-related Problem/Condition Clinical Trial

— ARPEGE BioM  

Official title:

Integrative Molecular Analysis of Individual Radiosensitivity Among a Population of Pediatric Patients Treated With Radiation in Eastern France.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02827552
• Other study ID #: 2015-A00975-44
• Status: Terminated
• Phase: N/A
• Start date: March 13, 2017
• Est. completion date: February 7, 2020

Study information

• Verified date: February 2021
• Source: Institut de Cancérologie de Lorraine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to explore prospectively the distribution of individual radiosensitivity in the pediatric population and to determine the predictive power of individual radiosensitivity biomarkers from an immunofluorescence technique on primary dermal fibroblasts

Description:

900 children and adolescents benefit from radiation each year in France. The mean age at diagnosis is 5 years; life expectancy for the 80% of them who could cure is long, and the incidence of radiation-related acute and mainly late complications - not evaluated to date - could exceed that of adults. Dysfunction of irradiated organs and growth disorders are specific to the pediatric subpopulation. Individual radiosensitivity of children and adolescents is unknown at this time, probably with large variability depending on the age when considering the changes in metabolic functions throughout growth. These complications are largely attributable to inter individual constitutional variations of cellular response to DNA damage.

Subject to radiation-induced DNA damages such as double-strand breaks (DSB), cells reacts by triggering a whole series of phosphorylation events coordinated within multi protein complexes whose interplay is still misknown (DNA damage response i.e. DDR). Indirect Immunofluorescence cell scanning has revolutionized radiation biology research by permitting the detection of individual DSB in each cell nucleus in a dose range from 1 mGy to 10 Gy. This technique has notably confirmed that yield of unrepaired DSB is correlated with cell RS. From a broad spectrum of human radiosensitive skin fibroblast cell lines, the Inserm CRU 1052 team proposed a general model of DSB signaling and repair and a molecular assay to stratify patients according to their individual RS.

ARPEGE biomarqueurs is a prospective multicenter study to prospectively evaluate with this assay the RS of children and adolescents treated over a year in all pediatric oncology departments of the Region Grand Est and set thresholds in this population. 150 children are thus potentially includable in different centers. The assay will be performed on primary fibroblasts cultured from a skin biopsy taken at diagnosis. The RS of patients will be measured in blind. Confusion factors such as irradiated volume, skin phototype, previous chemotherapy regimen, smoking, comorbities (diabetes, immunodeficiency, chronic inflammatory disease ...) will be reported. In parallel the RT-acute toxicity will be reported according to NCI-CTCAE v4.0 reference scale three months of the completion of RT then periodically during 15 years.

Screening hypersensitive patients would be a major step forward in the management of cancers, opening a view to personalized medicine.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 40
• Est. completion date: February 7, 2020
• Est. primary completion date: February 7, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

Inclusion Criteria:

• Children < 18 years old

• Patient with an indication of radiotherapy

• Patient must be affiliated to a social security system

• Patient under parental autority

• Ability to provide an informed written consent form

Exclusion Criteria:

• Contraindications for skin biopsy

• Contraindications for radiotherapy

• Referred to palliative radiotherapy

• Prior radiotherapy in the same area

• Indication of hypofractionated radiotherapy

• Patient monitoring impossible

• Patients deprived of liberty or under supervision

Related Conditions & MeSH terms

• Cancer-related Problem/Condition

Intervention

Other:
• skin biopsy
skin biopsy performed prior radiation to characterize in blind the individual radiosensitivity of the patient

Locations

Country	Name	City	State
France	CHU de Besançon	Besançon
France	CHU de Dijon	Dijon
France	Georges-François-Leclerc	Dijon
France	Centre Léon Bérard	Lyon
France	CHU de Reims	Reims
France	Centre Paul Strauss	Strasbourg
France	Hôpital de Hautepierre	Strasbourg
France	CHRU toulouse	Toulouse
France	IUCT Oncopole	Toulouse
France	CHRU Nancy	Vandoeuvre-lès-Nancy
France	Institut de Cancérologie de Lorraine	Vandoeuvre-lès-Nancy

Sponsors (1)

Lead Sponsor	Collaborator
Institut de Cancérologie de Lorraine

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	skin fibroblast radiosenstivity	residual double-strand breaks 24h after ex vivo radiation assessed with indirect immunofluorescence (gammaH2AX marker).	up to 5 months
Secondary	early cutaneous, mucosal and hematological early radiation toxicity	early radiation toxicity pattern assessed according to CTACAE v4.0 scale	3 months
Secondary	pATM nucleoshuttling	pATM foci counted 10 minutes and 1 hour after ex vivo radiation assessed with indirect immunofluorescence (pATM marker).	up to 5 months
Secondary	mean micronuclei number	micronuclei counted 24 hours after ex vivo radiation assessed with indirect immunofluorescence (DAPI marker).	up to 5 months
Secondary	late radiation toxicity	deterministic tissue effects as well as secondary malignancies occurring in radiation field more than 3 months and up to 15 years after RT, using CTCAE v4.0 scale	15 years