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

Purpose

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.

Condition	Intervention
Breast Cancer	Biological: Blood and tumor sample

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label
Official Title:	Study of the Response to a Neoadjuvant Chemotherapy Based on the Antitumor Immune Response in Localized Breast Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

U.S. FDA Resources

Further study details as provided by Centre Leon Berard:

Primary Outcome Measures:

Determine the correlation between histopathological response (pCR) and induction of tumor immunity in response to neoadjuvant chemotherapy [ Time Frame: Day (D) 1 chemotherapy (CT) n°1, D1 CT n°3, Surgery, 6 month post surgery ] [ Designated as safety issue: No ]
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:

Evolution of the immune profile during management of localized breast cancer [ Time Frame: D1 CT n°1, D1 CT n°3, Surgery, 6 month post surgery ] [ Designated as safety issue: No ]
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 [ Time Frame: D1 CT n°1, D1 CT n°3, Surgery, 6 month post surgery ] [ Designated as safety issue: No ]
Analysis of P2X7 and TLR4 polymorphisms on circulating cells (plasma)
Determination of relapse risk based on biological characteristics identified [ Time Frame: At the end of the study (5 years of follow-up) ] [ Designated as safety issue: No ]
Progression-free survival
Determining the risk of death based on biological characteristics identified [ Time Frame: At the end of the study (5 years of follow-up) ] [ Designated as safety issue: No ]
Overall survival

Estimated Enrollment:	40
Study Start Date:	December 2011
Estimated Study Completion Date:	December 2018
Estimated Primary Completion Date:	December 2018 (Final data collection date for primary outcome measure)

Intervention Details:

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).

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01440413

Contacts

Contact: Séverine GUILLEMAUT	+33 4 78 78 29 68	severine.guillemaut@lyon.unicancer.fr
Contact: Valérie FOUILLAT	+33 4 78 78 79 39	valerie.fouillat@lyon.unicancer.fr

Locations

France
Centre Georges François Leclerc	Active, not recruiting
DIJON Cedex, France, 21079
Centre Leon Berard	Recruiting
LYON Cedex 08, France, 69373
Principal Investigator: Olivier TREDAN, MD
Sub-Investigator: Thomas BACHELOT, MD
Sub-Investigator: Pierre BIRON, MD
Sub-Investigator: Jean-Yves BLAY, MD
Sub-Investigator: Jean-Paul GUASTALLA, MD
Sub-Investigator: Pierre-Etienne HEUDEL, MD
Sub-Investigator: Sana Intidhar LABIDI-GALY, MD
Sub-Investigator: Isabelle RAY-COQUARD, MD
Sub-Investigator: Paul REBATTU, MD

Sponsors and Collaborators

Centre Leon Berard

Investigators

Principal Investigator:

Olivier TREDAN, MD

Centre Leon Berard

More Information

Publications:

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Responsible Party:	Centre Leon Berard
ClinicalTrials.gov Identifier:	NCT01440413 History of Changes
Other Study ID Numbers:	BREAST IMMUN, ET11-059
Study First Received:	September 14, 2011
Last Updated:	November 13, 2012
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Centre Leon Berard:

anti-tumor immune response
neo-adjuvant chemotherapy
relapse
long term survival
histo-pathological response

tumor cell death
tumor associated antigens
Calreticulin
Localized breast cancer

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on May 22, 2013

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