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

Breast Cancer Clinical Trial

— BREAST IMMUN  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01440413
• Other study ID #: BREAST IMMUN
• Secondary ID: ET11-059
• Status: Active, not recruiting
• Phase: N/A
• Start date: December 2011
• Est. completion date: December 2020

Study information

• Verified date: March 2020
• Source: Centre Leon Berard
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: December 2020
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• Blood and tumor sample
Blood samples will be collected on the first day of the first cycle of chemotherapy (before injection of chemotherapy), on the first day of the third cycle (before injection of chemotherapy), on day of surgery and 6 months after surgery and in case of relapse. Tumor samples will be collected on diagnosis, on surgery and on the first day of the third chemotherapy course (optional).

Locations

Country	Name	City	State
France	Centre Georges François Leclerc	DIJON Cedex
France	Centre Leon Berard	LYON Cedex 08

Sponsors (1)

Lead Sponsor	Collaborator
Centre Leon Berard

Country where clinical trial is conducted

France, 

References & Publications (24)

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* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the correlation between histopathological response (pCR) and induction of tumor immunity in response to neoadjuvant chemotherapy	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).	Day (D) 1 chemotherapy (CT) n°1, D1 CT n°3, Surgery, 6 month post surgery
Secondary	Evolution of the immune profile during management of localized breast cancer	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	D1 CT n°1, D1 CT n°3, Surgery, 6 month post surgery
Secondary	Analysis of genetic polymorphisms	Analysis of P2X7 and TLR4 polymorphisms on circulating cells (plasma)	D1 CT n°1, D1 CT n°3, Surgery, 6 month post surgery
Secondary	Determination of relapse risk based on biological characteristics identified	Progression-free survival	At the end of the study (5 years of follow-up)
Secondary	Determining the risk of death based on biological characteristics identified	Overall survival	At the end of the study (5 years of follow-up)