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RNA and Heat Shock Protein Biomarkers in Radiation-induced Fibrosis in Breast Cancer (SPLICI-Rad)

Primary Purpose

Breast Carcinoma, Fibrosis

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
skin biopsies
blood samples
Sponsored by
Institut de Cancérologie de Lorraine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Breast Carcinoma focused on measuring Skin biopsy, Radiotherapy, RNA biomarker, HSP biomarker, Exon junction array, Gene expression, Radiosensitivity prediction

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • women
  • age ≥ 18 and <70 years old
  • non metastatic disease
  • ECOG performance status 0 or 1
  • chest size ≤ 110 cm et bra size <D
  • absence of reconstructive breast surgery
  • patient able to undergo blood samples (haematological conditions allowing blood sample)
  • non-evolving carcinological disease
  • absence of systemic inflammatory disease (other than scleroderma) or diabetes
  • no inflammatory ou infectious flare on biopsy site at the time of inclusion
  • invasive or in situ breast carcinoma
  • ability to provide an informed written consent form
  • affiliation to a social security system

Then stratification into two groups :

group 1 : radio-sensitive patients

  • Post-operative radiotherapy completed at least 6 months ago AND
  • radiation induced dermal and/or soft tissue toxicity (dermatitis, fibrosis, atrophy) rated > 2 (CTCAE v4.0 scale)

group 2 : radio-tolerant (control) patients

  • Post-operative radiotherapy completed more than 4 years ago AND
  • radiation induced dermal and/or soft tissue toxicity (dermatitis, fibrosis, atrophy) rated ≤1 (CTCAE v4.0 scale) .

Exclusion Criteria:

  • age <18 or > 70 years old
  • evolutive cancer / metastatic disease
  • chest size > 110 cm et bra size ≥ D
  • previous reconstructive breast surgery
  • ECOG performance status > 1
  • systemic inflammatory disease or diabetes
  • inflammatory ou infectious flare on biopsy site at the time of inclusion, very significant ulceration in the treated breast
  • anemic patients
  • use of oral anticoagulants
  • pregnant or likely to be in 6 months
  • patients deprived of liberty or under supervision
  • non-affiliation to a social security system

Sites / Locations

  • Institut de Cancérologie de Lorraine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Biomarkers

Arm Description

Outcomes

Primary Outcome Measures

Global mRNA alternative splicing and expression of non-coding RNAs profiles in healthy dermal fibroblasts
frequency of inclusion of individual exons within the set of mRNA isoforms (overall splicing profile) and variation in expression of non-coding RNAs

Secondary Outcome Measures

Transcriptomic signature of pathological induced fibrosis when comparing the primary outcome between the two populations on cultured fibroblasts
Transcriptomic signature of pathological induced fibrosis when comparing the primary outcome between the two populations on serum
Individual radiosensitivity on healthy dermal fibroblasts
The micronuclei will be counted 24 hours after ex vivo irradiation with an indirect immunofluorescence assay (53BP1 + pATM antibodies)
Comparison of the overall mRNA splicing and non-coding RNA expression profiles between non irradiated and irradiated dermal fibroblasts in the same individual
Changes in cellular distribution of the main non-coding RNAs whose expression varies significantly within the pre-identified signature between the 2 groups of patients
The cellular distribution is defined as the compartment (nucleoplasm, nucleolus, intra-nuclear corpuscles, cytosol, RE, mitochondria ...) marked by the fluorescent probe labeled to the non-coding RNAs of interest (RNA-FISH)
seric HSP proteins potentially predictive of pathological induced fibrosis
HSP27, HSP70 and αB crystalline measured in serum with ELISA assay
Cellular distribution of specific HSP on fibroblast culture in each group of patients
immunolabeling of HSPs and spatial mapping and sub-nuclear distributions
Potential interactions between DNA damage response proteins and candidate HSP
Collocation of HSPs with pATM and 53-BP1 (confocal microscopy / FLIM)

Full Information

First Posted
December 19, 2016
Last Updated
August 7, 2018
Sponsor
Institut de Cancérologie de Lorraine
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1. Study Identification

Unique Protocol Identification Number
NCT03000764
Brief Title
RNA and Heat Shock Protein Biomarkers in Radiation-induced Fibrosis in Breast Cancer
Acronym
SPLICI-Rad
Official Title
Study of RNA and Heat Shock Protein (HSP) Derived Biomarkers in Radiation-induced Fibrosis in Patients Treated for Breast Cancer.
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
May 10, 2017 (Actual)
Primary Completion Date
April 18, 2018 (Actual)
Study Completion Date
April 25, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut de Cancérologie de Lorraine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to seeking a molecular signature of pathological radiation induced fibrosis based on the response of skin fibroblasts after irradiation, comparing two groups of patients distinguished by their individual radiosensitivity. The signature will integrate recent insights in terms of alternative splicing of mRNAs and level of expression of non-coding RNAs, particularly long non-coding RNAs, snRNAs, snoRNAs and microRNAs. In each group each expression patterns of candidate HSP proteins potentially predictive of pathological radiation induced fibrosis (HSP27, HSP70, αβ crystalline) in the serum and on cell culture will be characterized.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Carcinoma, Fibrosis
Keywords
Skin biopsy, Radiotherapy, RNA biomarker, HSP biomarker, Exon junction array, Gene expression, Radiosensitivity prediction

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Biomarkers
Arm Type
Experimental
Intervention Type
Other
Intervention Name(s)
skin biopsies
Intervention Description
Biopsies (12 G) will be performed : in non-irradiated breast skin in irradiated breast skin
Intervention Type
Other
Intervention Name(s)
blood samples
Intervention Description
blood samples are collected: 10 ml in EDTA tube 2,5 ml in PAXgene Blood RNA tube 4 ml in EDTA tube
Primary Outcome Measure Information:
Title
Global mRNA alternative splicing and expression of non-coding RNAs profiles in healthy dermal fibroblasts
Description
frequency of inclusion of individual exons within the set of mRNA isoforms (overall splicing profile) and variation in expression of non-coding RNAs
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Transcriptomic signature of pathological induced fibrosis when comparing the primary outcome between the two populations on cultured fibroblasts
Time Frame
6 months
Title
Transcriptomic signature of pathological induced fibrosis when comparing the primary outcome between the two populations on serum
Time Frame
6 months
Title
Individual radiosensitivity on healthy dermal fibroblasts
Description
The micronuclei will be counted 24 hours after ex vivo irradiation with an indirect immunofluorescence assay (53BP1 + pATM antibodies)
Time Frame
6 months
Title
Comparison of the overall mRNA splicing and non-coding RNA expression profiles between non irradiated and irradiated dermal fibroblasts in the same individual
Time Frame
6 months
Title
Changes in cellular distribution of the main non-coding RNAs whose expression varies significantly within the pre-identified signature between the 2 groups of patients
Description
The cellular distribution is defined as the compartment (nucleoplasm, nucleolus, intra-nuclear corpuscles, cytosol, RE, mitochondria ...) marked by the fluorescent probe labeled to the non-coding RNAs of interest (RNA-FISH)
Time Frame
6 months
Title
seric HSP proteins potentially predictive of pathological induced fibrosis
Description
HSP27, HSP70 and αB crystalline measured in serum with ELISA assay
Time Frame
6 months
Title
Cellular distribution of specific HSP on fibroblast culture in each group of patients
Description
immunolabeling of HSPs and spatial mapping and sub-nuclear distributions
Time Frame
6 months
Title
Potential interactions between DNA damage response proteins and candidate HSP
Description
Collocation of HSPs with pATM and 53-BP1 (confocal microscopy / FLIM)
Time Frame
6 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: women age ≥ 18 and <70 years old non metastatic disease ECOG performance status 0 or 1 chest size ≤ 110 cm et bra size <D absence of reconstructive breast surgery patient able to undergo blood samples (haematological conditions allowing blood sample) non-evolving carcinological disease absence of systemic inflammatory disease (other than scleroderma) or diabetes no inflammatory ou infectious flare on biopsy site at the time of inclusion invasive or in situ breast carcinoma ability to provide an informed written consent form affiliation to a social security system Then stratification into two groups : group 1 : radio-sensitive patients Post-operative radiotherapy completed at least 6 months ago AND radiation induced dermal and/or soft tissue toxicity (dermatitis, fibrosis, atrophy) rated > 2 (CTCAE v4.0 scale) group 2 : radio-tolerant (control) patients Post-operative radiotherapy completed more than 4 years ago AND radiation induced dermal and/or soft tissue toxicity (dermatitis, fibrosis, atrophy) rated ≤1 (CTCAE v4.0 scale) . Exclusion Criteria: age <18 or > 70 years old evolutive cancer / metastatic disease chest size > 110 cm et bra size ≥ D previous reconstructive breast surgery ECOG performance status > 1 systemic inflammatory disease or diabetes inflammatory ou infectious flare on biopsy site at the time of inclusion, very significant ulceration in the treated breast anemic patients use of oral anticoagulants pregnant or likely to be in 6 months patients deprived of liberty or under supervision non-affiliation to a social security system
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
VOGIN GUILLAUME, MD, PhD
Organizational Affiliation
Institut de Cancérologie de Lorraine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
BEHM-ANSMANT Isabelle, PhD
Organizational Affiliation
UMR 7365 CNRS-Université de Lorraine, IMoPA
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut de Cancérologie de Lorraine
City
Vandœuvre-lès-Nancy
ZIP/Postal Code
54519
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

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RNA and Heat Shock Protein Biomarkers in Radiation-induced Fibrosis in Breast Cancer

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