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

• ClinicalTrials.gov Identifier: NCT03252717
• Recruitment Status: Unknown
• First Posted: August 17, 2017
• Last Update Posted: October 20, 2020
• Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
• Information provided by (Responsible Party): Institut du Cancer de Montpellier - Val d'Aurelle

Study Description

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

Study Design

• 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
• Actual Primary Completion Date: August 31, 2017
• Estimated Study Completion Date: August 2022

Arms and Interventions

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

Outcome Measures

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.

Eligibility Criteria

• 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

Contacts and Locations

Locations

France

Institut régional du Cancer de Montpellier

Montpellier, France, 34298

Sponsors and Collaborators

Institut du Cancer de Montpellier - Val d'Aurelle

Investigators

• Study Chair: david azria; Institut régional du Cancer de Montpellier

More Information

• 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
• Last Update Posted: October 20, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Breast Neoplasms; Hypersensitivity; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Immune System Diseases