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

Breast Carcinoma Clinical Trial

— SPLICI-Rad  

Official title:

Study of RNA and Heat Shock Protein (HSP) Derived Biomarkers in Radiation-induced Fibrosis in Patients Treated for Breast Cancer.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03000764
• Other study ID #: 2016-A00592-49
• Status: Completed
• Phase: N/A
• Start date: May 10, 2017
• Est. completion date: April 25, 2018

Study information

• Verified date: August 2018
• Source: Institut de Cancérologie de Lorraine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 25, 2018
• Est. primary completion date: April 18, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Carcinoma
• Breast Neoplasms
• Fibrosis

Intervention

Other:
• skin biopsies
Biopsies (12 G) will be performed : in non-irradiated breast skin in irradiated breast skin
• blood samples
blood samples are collected: 10 ml in EDTA tube 2,5 ml in PAXgene Blood RNA tube 4 ml in EDTA tube

Locations

Country	Name	City	State
France	Institut de Cancérologie de Lorraine	Vandœuvre-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	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	6 months
Secondary	Transcriptomic signature of pathological induced fibrosis when comparing the primary outcome between the two populations on cultured fibroblasts		6 months
Secondary	Transcriptomic signature of pathological induced fibrosis when comparing the primary outcome between the two populations on serum		6 months
Secondary	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)	6 months
Secondary	Comparison of the overall mRNA splicing and non-coding RNA expression profiles between non irradiated and irradiated dermal fibroblasts in the same individual		6 months
Secondary	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)	6 months
Secondary	seric HSP proteins potentially predictive of pathological induced fibrosis	HSP27, HSP70 and aB crystalline measured in serum with ELISA assay	6 months
Secondary	Cellular distribution of specific HSP on fibroblast culture in each group of patients	immunolabeling of HSPs and spatial mapping and sub-nuclear distributions	6 months
Secondary	Potential interactions between DNA damage response proteins and candidate HSP	Collocation of HSPs with pATM and 53-BP1 (confocal microscopy / FLIM)	6 months