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Description of Individual Radiosensitivity With Molecular Biomarkers in a Pediatric Oncology Population (ARPEGE BioM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02827552
Recruitment Status : Recruiting
First Posted : July 11, 2016
Last Update Posted : December 4, 2019
Information provided by (Responsible Party):
Institut de Cancérologie de Lorraine

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

Condition or disease Intervention/treatment Phase
Cancer-related Problem/Condition Other: skin biopsy Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 222 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Integrative Molecular Analysis of Individual Radiosensitivity Among a Population of Pediatric Patients Treated With Radiation in Eastern France.
Actual Study Start Date : March 13, 2017
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2034

Arm Intervention/treatment
N/A (not a randomized study)
Other: skin biopsy
skin biopsy performed prior radiation to characterize in blind the individual radiosensitivity of the patient

Primary Outcome Measures :
  1. skin fibroblast radiosenstivity [ Time Frame: up to 5 months ]
    residual double-strand breaks 24h after ex vivo radiation assessed with indirect immunofluorescence (gammaH2AX marker).

Secondary Outcome Measures :
  1. early cutaneous, mucosal and hematological early radiation toxicity [ Time Frame: 3 months ]
    early radiation toxicity pattern assessed according to CTACAE v4.0 scale

  2. pATM nucleoshuttling [ Time Frame: up to 5 months ]
    pATM foci counted 10 minutes and 1 hour after ex vivo radiation assessed with indirect immunofluorescence (pATM marker).

  3. mean micronuclei number [ Time Frame: up to 5 months ]
    micronuclei counted 24 hours after ex vivo radiation assessed with indirect immunofluorescence (DAPI marker).

  4. late radiation toxicity [ Time Frame: 15 years ]
    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

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02827552

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Contact: MERLIN JEAN LOUIS, PR + 33 3 83 59 83 07
Contact: TOSTI PRISCILLIA, PhD + 33 3 83 59 86 57

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CHU de Besançon Recruiting
Besançon, France, 25 000
Contact: LAITHIER Véronique, MD   
CHU de Dijon Recruiting
Dijon, France, 21 000
Contact: BRIANDET Claire, MD   
Georges-François-Leclerc Recruiting
Dijon, France, 21 000
Contact: TRUC Gilles, MD   
Centre Léon Bérard Recruiting
Lyon, France, 69 000
Contact: CLAUDE Line, MD   
CHU de Reims Recruiting
Reims, France, 51 100
Contact: PLUCHART Claire, MD   
Centre Paul Strauss Recruiting
Strasbourg, France, 67 065
Contact: VIGNERON Céline, MD   
Hôpital de Hautepierre Recruiting
Strasbourg, France, 67 098
Contact: ENTZ-WERLE Natacha, MD   
CHRU toulouse Recruiting
Toulouse, France, 31059
Contact: GAMBART Marion, MD   
IUCT Oncopole Recruiting
Toulouse, France, 31059
Contact: LAPRIE Anne, MD   
Contact: DUCASSOU Anne, M/D   
Institut de Cancérologie de Lorraine Recruiting
Vandoeuvre-lès-Nancy, France, 54 500
Contact: VOGIN Guillaume, MD   
Contact: BERNIER CHASTAGNER Valérie, MD   
CHRU Nancy Recruiting
Vandoeuvre-lès-Nancy, France, 54500
Contact: CHASTAGNER Pascal, MD   
Sponsors and Collaborators
Institut de Cancérologie de Lorraine
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Principal Investigator: VOGIN GUILLAUME, MD,PhD Institut de Cancérologie de Lorraine
Principal Investigator: BERNIER CHASTAGNER VALERIE, MD Institut de Cancérologie de Lorraine
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Institut de Cancérologie de Lorraine Identifier: NCT02827552    
Other Study ID Numbers: 2015-A00975-44
First Posted: July 11, 2016    Key Record Dates
Last Update Posted: December 4, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Institut de Cancérologie de Lorraine:
pediatric oncology