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Predictive Role of New Biomarkers for Hypersensitive Patients to Radiation in Breast Cancer (BIORISE) (BIORISE)

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ClinicalTrials.gov Identifier: NCT03252717
Recruitment Status : Recruiting
First Posted : August 17, 2017
Last Update Posted : August 17, 2017
Sponsor:
Information provided by (Responsible Party):
Institut du Cancer de Montpellier - Val d'Aurelle

Brief Summary:
To confirm the protein expression level in radiation-induced late effects patients and to determine the performance value, in particular the positive predictive value, of a blood test based on the dosage of a panel of five proteins, it is necessary to validate these preliminary results by a prospective study on a large cohort of patients.

Condition or disease Intervention/treatment Phase
Breast Cancer Biological: Blood sample Not Applicable

Detailed Description:

Molecular mechanisms involved in radiation-induced responses are complex, and proteomic approaches can be used to better understand the overall reaction process of ionizing radiation and to identify potential radio-sensitive predictive markers. Until now, few publications have addressed the determination of radiosensitive patients.

Based on our previous results and in order to improve the positive predictive value of the radiation induced late effect assay, we developed a quantitative proteomic approach to identify predictive radiobiological markers in patients with severe toxicity. First, four patients were selected with a low RILA value from the prospective studies mentioned above. Two patients had no toxicity at least four years after the end of treatment whereas two others patients developed a severe toxicity greater than grade 2. T-lymphocytes have been isolated from whole blood and half of them have been irradiated in vitro. It will then performed a quantitative proteomics workflow using an 8-plex iTRAQ labeling and after several fractionations to optimize resolution of analysis (off gel fractionation followed by nanoliquid chromatography), proteins were identified by tandem mass spectrometry (4800 plus MALDI TOF/TOF). More than 1300 total proteins were identified with high confidence (95%, one unique peptide). At 0 Gy, 135 proteins were differentially expressed between patients with or without severe radio-induced toxicity. In irradiated T-lymphocytes (8 Gy), 107 proteins were differentially expressed between patients with or without severe radio-induced toxicity. Among them, five proteins (AK2, adenylate kinase 2; IDH2, isocitrate dehydrogenase 2 (NADP+); ANX1, annexin 1; APEX1, DNA-(apurinic or apyrimidinic site) lyase, and HSC70, Heat shock cognate 71 kDa) with the highest protein expression ratio (>1.5) and that showed no difference expression ratio in 0 Gy controls, were selected for consecutive validation. These proteins are involved in several mechanisms including metabolism and energy production, apoptosis, calcium binding protein, and DNA damages repair. These five proteins are currently the subject of patent application.

Then,10 other patients will be recruited (5 patients with grade ≥ 2 breast fibrosis and 5 patients without toxicity) who presented a low RILA value to validate proteins expression by western-blotting. Results showed that all proteins were overexpressed in irradiated T-lymphocytes patients with severe toxicity comparatively to patients without toxicity.

However, to confirm the protein expression level in radiation-induced late effects patients and to determine the performance value, in particular the positive predictive value, of a blood test based on the dosage of a panel of five proteins, it is necessary to validate these preliminary results by a prospective study on a large cohort of patients

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Radiation-induced Late Side-effects: Predictive Role of New Biomarkers for Selecting Hypersensitive Patients to Ionizing Radiation in Breast Cancer (BIORISE)
Study Start Date : August 2014
Estimated Primary Completion Date : August 2017
Estimated Study Completion Date : August 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: blood sample
Pre-treatment blood samples will be collected: 8 samples
Biological: Blood sample

Pre-treatment blood samples will be collected for downstream analyses:

  • Three 6 ml EDTA samples for proteomic and genomic work package
  • One 6 ml dry sample for auto-antibodies analysis in the immunology work package
  • Two 4 ml EDTA samples for DNA extraction in the immunology work package
  • Two 2.5 ml PAX Gene sample for RNA extraction in the immunology work package and the non-irradiated control in the genomic work package




Primary Outcome Measures :
  1. blood sample to assess dosage of 5 proteins [ Time Frame: through study completion, an average of 5 years ]
    Confirm the predictive value, of a blood test based on the dosage of a panel of five (5) proteins: AK2 - IDH2 - ANX1- APEX1 - HSC70 in radiation-induced late side effects after breast-conserving surgery and curative intent adjuvant radiotherapy.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients suitable for adjuvant radiotherapy for cancer of the breast (invasive or in situ) including breast patients receiving neo-adjuvant chemotherapy. Patients receiving chemotherapy should have completed their course of chemotherapy (anthracyclines) at least one month prior to radiotherapy commencing.
  • No other malignancy prior to treatment for the specified tumour types except basal cell or squamous cell carcinoma of the skin
  • No evidence of distant metastases
  • Patients able to provide a venous blood sample
  • Willingness and ability to comply with scheduled visits, treatment plans and available for follow up
  • Greater than 18 years of age; no upper age limit
  • The capacity to understand the patient information sheet and the ability to provide written informed consent
  • Patients must be affiliated to a Social Security System

Exclusion Criteria:

  • Patients with metastatic disease
  • Prior irradiation at the same site
  • Planned use of protons
  • Breast patients receiving concomitant chemo-radiation
  • Male breast cancer patients
  • Mastectomy patients
  • Bilateral breast cancer
  • Mental disability or patient otherwise unable to give informed consent
  • Limited life expectancy due to co-morbidity
  • Pregnant patients
  • Partial breast irradiation
  • Patients with breast implants if not removed during surgery

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 ClinicalTrials.gov identifier (NCT number): NCT03252717


Contacts
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Contact: david azria 0033467613102 david.azria@icm.unicancer.fr

Locations
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France
Institut régional du Cancer de Montpellier Recruiting
Montpellier, France, 34298
Contact: David AZRIA    0033467613102    david.azria@icm.unicancer.fr   
Sponsors and Collaborators
Institut du Cancer de Montpellier - Val d'Aurelle
Investigators
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Study Chair: david azria Institut régional du Cancer de Montpellier
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Responsible Party: Institut du Cancer de Montpellier - Val d'Aurelle
ClinicalTrials.gov Identifier: NCT03252717    
Other Study ID Numbers: ICM-URC-2014/22
First Posted: August 17, 2017    Key Record Dates
Last Update Posted: August 17, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Breast Neoplasms
Hypersensitivity
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Immune System Diseases