Clinical trial NCT02827552: Description of Individual Radiosensitivity With Molecular Biomarkers in a Pediatric Oncology Population
Official title: Integrative Molecular Analysis of Individual Radiosensitivity Among a Population of Pediatric Patients Treated With Radiation in Eastern France.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Cancer-related Problem/Condition
Keywords: pediatric oncology
radiotherapy
radiosensitivity
Lead sponsor: Institut de Cancérologie de Lorraine
Sponsor class: OTHER
First posted: 2016-07-11
Enrollment: 40
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief 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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: skin fibroblast radiosenstivity
timeFrame: up to 5 months
Secondary outcomes:
measure: early cutaneous, mucosal and hematological early radiation toxicity
timeFrame: 3 months
measure: pATM nucleoshuttling
timeFrame: up to 5 months
measure: mean micronuclei number
timeFrame: up to 5 months
measure: late radiation toxicity
timeFrame: 15 years
Other outcomes:
Locations:
city: Besançon
country: France
facility: CHU de Besançon
city: Dijon
country: France
facility: CHU de Dijon
city: Dijon
country: France
facility: Georges-François-Leclerc
city: Lyon
country: France
facility: Centre Léon Bérard
city: Reims
country: France
facility: CHU de Reims
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Strasbourg
country: France
facility: Hôpital de Hautepierre
city: Toulouse
country: France
facility: CHRU toulouse
city: Toulouse
country: France
facility: IUCT Oncopole
city: Vandoeuvre-lès-Nancy
country: France
facility: Institut de Cancérologie de Lorraine
city: Vandoeuvre-lès-Nancy
country: France
facility: CHRU Nancy
Study officials:
affiliation: Institut de Cancérologie de Lorraine
name: VOGIN GUILLAUME, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut de Cancérologie de Lorraine
name: BERNIER CHASTAGNER VALERIE, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bernier-Chastagner V, Hettal L, Gillon V, Fernandes L, Huin-Schohn C, Vazel M, Tosti P, Salleron J, Francois A, Cerimele E, Perreira S, Peiffert D, Chastagner P, Vogin G. Validation of a high performance functional assay for individual radiosensitivity in pediatric oncology: a prospective cohort study (ARPEGE). BMC Cancer. 2018 Jul 6;18(1):719. doi: 10.1186/s12885-018-4652-7.