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NCT Number: NCT03000764

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

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.

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Key information

Conditions

Breast Carcinoma Breast Diseases Breast Neoplasms Fibrosis Neoplasms Neoplasms by Site Pathologic Processes Pathological Conditions, Signs and Symptoms Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year–70 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, 54519, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Skin biopsies

Other

Biopsies (12 G) will be performed :

  • in non-irradiated breast skin
  • in irradiated breast skin

Blood Samples

Other

blood samples are collected:

  • 10 ml in EDTA tube
  • 2,5 ml in PAXgene Blood RNA tube
  • 4 ml in EDTA tube

Primary outcomes

  1. Global mRNA alternative splicing and expression of non-coding RNAs profiles in healthy dermal fibroblasts

    Time frame: 6 months

    frequency of inclusion of individual exons within the set of mRNA isoforms (overall splicing profile) and variation in expression of non-coding RNAs

Secondary outcomes

  1. Transcriptomic signature of pathological induced fibrosis when comparing the primary outcome between the two populations on cultured fibroblasts

    Time frame: 6 months

  2. Transcriptomic signature of pathological induced fibrosis when comparing the primary outcome between the two populations on serum

    Time frame: 6 months

  3. Individual radiosensitivity on healthy dermal fibroblasts

    Time frame: 6 months

    The micronuclei will be counted 24 hours after ex vivo irradiation with an indirect immunofluorescence assay (53BP1 + pATM antibodies)

  4. 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

  5. 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

    Time frame: 6 months

    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. seric HSP proteins potentially predictive of pathological induced fibrosis

    Time frame: 6 months

    HSP27, HSP70 and αB crystalline measured in serum with ELISA assay

  7. Cellular distribution of specific HSP on fibroblast culture in each group of patients

    Time frame: 6 months

    immunolabeling of HSPs and spatial mapping and sub-nuclear distributions

  8. Potential interactions between DNA damage response proteins and candidate HSP

    Time frame: 6 months

    Collocation of HSPs with pATM and 53-BP1 (confocal microscopy / FLIM)

Sponsors and collaborators

Lead sponsor

Institut de Cancérologie de Lorraine

Other

Registry information

Official study title

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

Acronym: SPLICI-Rad

Important dates

Study start
2017
Primary completion
2018
Study completion
2018
First posted
Dec 22, 2016
Registry last updated
Aug 8, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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