Study of the Response to a Neoadjuvant Chemotherapy Based on the Antitumor Immune Response in Localized Breast Cancer

Not Applicable

• Conditions: Breast Cancer

• Registration Number: NCT01440413
• Lead Sponsor: Centre Leon Berard

Brief Summary

This is a prospective, non-randomized study which aims to evaluate the response to a neoadjuvant chemotherapy according to the the antitumor immune response in localized breast cancer.

40 patients will be enrolled in the study. They will receive chemotherapy : 3 or 4 anthracycline cycles or 3 or 4 FEC-100 cycles followed by 3 or 4 taxane cycles.

Trastuzumab will be added to taxane for HER2+/Neu+ patients. Then, patients will be operated and receive an adjuvant treatment which will both depend on the investigator's appreciation.

Blood sample will be collected on the first day of the first chemotherapy cycle, on the first day of the third cycle, on surgery, 6 months after the surgery and in case of relapse.

Tumor sample will be collected on diagnosis as much as possible and on surgery.

Patients will be followed during 5 years.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-09-14
• Study First Submitted QC: 2011-09-23
• Study First Posted: 2011-09-26
• Study Start: 2011-12
• Primary Completion: 2018-12
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-23
• Last Update Posted: 2020-03-24
• Study Completion: 2020-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 40

Inclusion Criteria

• Histologically proven localized breast cancer required anthracycline chemotherapy +/- trastuzumab before surgery
• Age > 18 years
• Chemotherapy with 3 anthracycline cycles to begin (doxorubicin or epirubicin)
• Any previous treatment for this cancer
• Performance Status <= 1
• Agreement for the conservation of biological samples
• Covered by an medical insurance
• Signed written informed consent form
• Availability of tumoral sample collected at diagnosis

Exclusion Criteria

• Previous surgery for the breast cancer
• Already under chemotherapy before the first blood sample
• Previous Antitumoral treatment
• Under immunosuppressive treatment
• Under corticoids during the 15 days before enrollment
• History of concomitant cancer except if it has been cured for at least 5 years
• History of lymphoma or breast sarcoma
• History of chronic inflammatory disease or autoimmune disease, hepatitis B or C or immune dysfunction disease (including HIV-positive stage AIDS) known
• History of other disease which is discrepant with this study
• Deprived of liberty by court or administrative decision
• Pregnant or breastfeeding women or with no use of effective birth control methods for women of childbearing potential

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Determine the correlation between histopathological response (pCR) and induction of tumor immunity in response to neoadjuvant chemotherapy	Day (D) 1 chemotherapy (CT) n°1, D1 CT n°3, Surgery, 6 month post surgery	Rate of histopathologic response (IHC). Analysis of lymphocyte subpopulations (whole blood - flow cytometry). Analysis of the frequency of immune cells, the phenotype and functional status on the site of the tumor (fixed tissue - IHC). Analysis of the functional status of sub-populations of DC and lymphocytes of innate immunity (fresh whole blood - flow cytometry). Analysis of BCR and TCR repertoires (mononuclear cells - PCR). Identification of TAA expressed by the tumor (plasma, tumor - ELISA, IHC).Analysis of the humoral response against TAA (plasma - ELISA).

Secondary Outcome Measures

Name	Time	Method
Evolution of the immune profile during management of localized breast cancer	D1 CT n°1, D1 CT n°3, Surgery, 6 month post surgery	Analysis in plasma of the rate of apoptotic tumor cells, of TAA (CEA and MUC1 ELISA), of tumor DNA and endogenous ligands of TLR (HMGB1 ELISA) Assay of cytokines and chemokines in plasma Analysis of the expression of proteins involved in the translocation of CRT to the cell surface (fixed-frozen tissue - IHC or immunoblotting) Analysis on the tumor (IHC or immunoblotting) of degradation of BAP31, activation of caspase 8/Bax/Bak, phosphorylation of eIF2 and exposure of surface CRT, KDEL receptor and ERp57
Analysis of genetic polymorphisms	D1 CT n°1, D1 CT n°3, Surgery, 6 month post surgery	Analysis of P2X7 and TLR4 polymorphisms on circulating cells (plasma)
Determination of relapse risk based on biological characteristics identified	At the end of the study (5 years of follow-up)	Progression-free survival
Determining the risk of death based on biological characteristics identified	At the end of the study (5 years of follow-up)	Overall survival

Trial Locations

Locations (2)

Centre Leon Berard; 🇫🇷 LYON Cedex 08, France

Centre Georges François Leclerc; 🇫🇷 DIJON Cedex, France