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

Primary Purpose

Breast Cancer

Status

Unknown status

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

Blood and tumor sample

About this trial

This is an interventional other trial for Breast Cancer focused on measuring anti-tumor immune response, neo-adjuvant chemotherapy, relapse, long term survival, histo-pathological response, tumor cell death, tumor associated antigens, Calreticulin, Localized breast cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

Centre Georges François Leclerc
Centre Leon Berard

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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

Analysis of genetic polymorphisms

Analysis of P2X7 and TLR4 polymorphisms on circulating cells (plasma)

Determination of relapse risk based on biological characteristics identified

Progression-free survival

Determining the risk of death based on biological characteristics identified

Overall survival

Full Information

NCT ID

NCT01440413

First Posted

September 14, 2011

Last Updated

March 23, 2020

Sponsor

Centre Leon Berard

1. Study Identification

Unique Protocol Identification Number

NCT01440413

Brief Title

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

Acronym

BREAST IMMUN

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Unknown status

Study Start Date

December 2011 (Actual)

Primary Completion Date

December 2018 (Actual)

Study Completion Date

December 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Centre Leon Berard

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

Keywords

anti-tumor immune response, neo-adjuvant chemotherapy, relapse, long term survival, histo-pathological response, tumor cell death, tumor associated antigens, Calreticulin, Localized breast cancer

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type

Biological

Intervention Name(s)

Blood and tumor sample

Intervention Description

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).

Primary Outcome Measure Information:

Title

Determine the correlation between histopathological response (pCR) and induction of tumor immunity in response to neoadjuvant chemotherapy

Description

Time Frame

Day (D) 1 chemotherapy (CT) n°1, D1 CT n°3, Surgery, 6 month post surgery

Secondary Outcome Measure Information:

Title

Evolution of the immune profile during management of localized breast cancer

Description

Time Frame

D1 CT n°1, D1 CT n°3, Surgery, 6 month post surgery

Title

Analysis of genetic polymorphisms

Description

Analysis of P2X7 and TLR4 polymorphisms on circulating cells (plasma)

Time Frame

D1 CT n°1, D1 CT n°3, Surgery, 6 month post surgery

Title

Determination of relapse risk based on biological characteristics identified

Description

Progression-free survival

Time Frame

At the end of the study (5 years of follow-up)

Title

Determining the risk of death based on biological characteristics identified

Description

Overall survival

Time Frame

At the end of the study (5 years of follow-up)

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Olivier TREDAN, MD

Organizational Affiliation

Centre Leon Berard

Official's Role

Principal Investigator

Facility Information:

Facility Name

Centre Georges François Leclerc

City

DIJON Cedex

ZIP/Postal Code

21079

Country

France

Facility Name

Centre Leon Berard

City

LYON Cedex 08

ZIP/Postal Code

69373

Country

France

12. IPD Sharing Statement

Citations:

PubMed Identifier

17704786

Citation

Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, Mignot G, Maiuri MC, Ullrich E, Saulnier P, Yang H, Amigorena S, Ryffel B, Barrat FJ, Saftig P, Levi F, Lidereau R, Nogues C, Mira JP, Chompret A, Joulin V, Clavel-Chapelon F, Bourhis J, Andre F, Delaloge S, Tursz T, Kroemer G, Zitvogel L. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med. 2007 Sep;13(9):1050-9. doi: 10.1038/nm1622. Epub 2007 Aug 19.

Results Reference

background

PubMed Identifier

10837075

Citation

Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K. Immunobiology of dendritic cells. Annu Rev Immunol. 2000;18:767-811. doi: 10.1146/annurev.immunol.18.1.767.

Results Reference

background

PubMed Identifier

17135638

Citation

Bates GJ, Fox SB, Han C, Leek RD, Garcia JF, Harris AL, Banham AH. Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol. 2006 Dec 1;24(34):5373-80. doi: 10.1200/JCO.2006.05.9584.

Results Reference

background

PubMed Identifier

16606972

Citation

Bear HD, Anderson S, Smith RE, Geyer CE Jr, Mamounas EP, Fisher B, Brown AM, Robidoux A, Margolese R, Kahlenberg MS, Paik S, Soran A, Wickerham DL, Wolmark N. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer:National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2006 May 1;24(13):2019-27. doi: 10.1200/JCO.2005.04.1665. Epub 2006 Apr 10.

Results Reference

background

PubMed Identifier

8636781

Citation

Blay JY, Chauvin F, Le Cesne A, Anglaret B, Bouhour D, Lasset C, Freyer G, Philip T, Biron P. Early lymphopenia after cytotoxic chemotherapy as a risk factor for febrile neutropenia. J Clin Oncol. 1996 Feb;14(2):636-43. doi: 10.1200/JCO.1996.14.2.636.

Results Reference

background

PubMed Identifier

15503313

Citation

Borg C, Ray-Coquard I, Philip I, Clapisson G, Bendriss-Vermare N, Menetrier-Caux C, Sebban C, Biron P, Blay JY. CD4 lymphopenia as a risk factor for febrile neutropenia and early death after cytotoxic chemotherapy in adult patients with cancer. Cancer. 2004 Dec 1;101(11):2675-80. doi: 10.1002/cncr.20688.

Results Reference

background

PubMed Identifier

17347129

Citation

Chapman C, Murray A, Chakrabarti J, Thorpe A, Woolston C, Sahin U, Barnes A, Robertson J. Autoantibodies in breast cancer: their use as an aid to early diagnosis. Ann Oncol. 2007 May;18(5):868-73. doi: 10.1093/annonc/mdm007. Epub 2007 Mar 7.

Results Reference

background

PubMed Identifier

11072789

Citation

Disis ML, Knutson KL, Schiffman K, Rinn K, McNeel DG. Pre-existent immunity to the HER-2/neu oncogenic protein in patients with HER-2/neu overexpressing breast and ovarian cancer. Breast Cancer Res Treat. 2000 Aug;62(3):245-52. doi: 10.1023/a:1006438507898.

Results Reference

background

PubMed Identifier

19843863

Citation

Domschke C, Schuetz F, Ge Y, Seibel T, Falk C, Brors B, Vlodavsky I, Sommerfeldt N, Sinn HP, Kuhnle MC, Schneeweiss A, Scharf A, Sohn C, Schirrmacher V, Moldenhauer G, Momburg F, Beckhove P. Intratumoral cytokines and tumor cell biology determine spontaneous breast cancer-specific immune responses and their correlation to prognosis. Cancer Res. 2009 Nov 1;69(21):8420-8. doi: 10.1158/0008-5472.CAN-09-1627. Epub 2009 Oct 20.

Results Reference

background

PubMed Identifier

16899776

Citation

Fan C, Oh DS, Wessels L, Weigelt B, Nuyten DS, Nobel AB, van't Veer LJ, Perou CM. Concordance among gene-expression-based predictors for breast cancer. N Engl J Med. 2006 Aug 10;355(6):560-9. doi: 10.1056/NEJMoa052933.

Results Reference

background

PubMed Identifier

16374613

Citation

Guckel B, Rentzsch C, Nastke MD, Marme A, Gruber I, Stevanovic S, Kayser S, Wallwiener D. Pre-existing T-cell immunity against mucin-1 in breast cancer patients and healthy volunteers. J Cancer Res Clin Oncol. 2006 Apr;132(4):265-74. doi: 10.1007/s00432-005-0064-6. Epub 2005 Dec 22.

Results Reference

background

PubMed Identifier

11181659

Citation

Loprinzi CL, Thome SD. Understanding the utility of adjuvant systemic therapy for primary breast cancer. J Clin Oncol. 2001 Feb 15;19(4):972-9. doi: 10.1200/JCO.2001.19.4.972.

Results Reference

background

PubMed Identifier

11556830

Citation

Ray-Coquard I, Ghesquiere H, Bachelot T, Borg C, Biron P, Sebban C, LeCesne A, Chauvin F, Blay JY; ELYPSE Study Group. Identification of patients at risk for early death after conventional chemotherapy in solid tumours and lymphomas. Br J Cancer. 2001 Sep 14;85(6):816-22. doi: 10.1054/bjoc.2001.2011.

Results Reference

background

PubMed Identifier

12684578

Citation

Remontet L, Esteve J, Bouvier AM, Grosclaude P, Launoy G, Menegoz F, Exbrayat C, Tretare B, Carli PM, Guizard AV, Troussard X, Bercelli P, Colonna M, Halna JM, Hedelin G, Mace-Lesec'h J, Peng J, Buemi A, Velten M, Jougla E, Arveux P, Le Bodic L, Michel E, Sauvage M, Schvartz C, Faivre J. Cancer incidence and mortality in France over the period 1978-2000. Rev Epidemiol Sante Publique. 2003 Feb;51(1 Pt 1):3-30.

Results Reference

background

PubMed Identifier

14555509

Citation

Rentzsch C, Kayser S, Stumm S, Watermann I, Walter S, Stevanovic S, Wallwiener D, Guckel B. Evaluation of pre-existent immunity in patients with primary breast cancer: molecular and cellular assays to quantify antigen-specific T lymphocytes in peripheral blood mononuclear cells. Clin Cancer Res. 2003 Oct 1;9(12):4376-86.

Results Reference

background

PubMed Identifier

15070799

Citation

Rosenberg SA. Shedding light on immunotherapy for cancer. N Engl J Med. 2004 Apr 1;350(14):1461-3. doi: 10.1056/NEJMcibr045001. No abstract available.

Results Reference

background

PubMed Identifier

15032588

Citation

Sakaguchi S. Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol. 2004;22:531-62. doi: 10.1146/annurev.immunol.21.120601.141122.

Results Reference

background

PubMed Identifier

15146561

Citation

Thomachot MC, Bendriss-Vermare N, Massacrier C, Biota C, Treilleux I, Goddard S, Caux C, Bachelot T, Blay JY, Menetrier-Caux C. Breast carcinoma cells promote the differentiation of CD34+ progenitors towards 2 different subpopulations of dendritic cells with CD1a(high)CD86(-)Langerin- and CD1a(+)CD86(+)Langerin+ phenotypes. Int J Cancer. 2004 Jul 10;110(5):710-20. doi: 10.1002/ijc.20146.

Results Reference

background

PubMed Identifier

15569976

Citation

Treilleux I, Blay JY, Bendriss-Vermare N, Ray-Coquard I, Bachelot T, Guastalla JP, Bremond A, Goddard S, Pin JJ, Barthelemy-Dubois C, Lebecque S. Dendritic cell infiltration and prognosis of early stage breast cancer. Clin Cancer Res. 2004 Nov 15;10(22):7466-74. doi: 10.1158/1078-0432.CCR-04-0684.

Results Reference

background

PubMed Identifier

11823860

Citation

van 't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R, Friend SH. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002 Jan 31;415(6871):530-6. doi: 10.1038/415530a.

Results Reference

background

PubMed Identifier

12490681

Citation

van de Vijver MJ, He YD, van't Veer LJ, Dai H, Hart AA, Voskuil DW, Schreiber GJ, Peterse JL, Roberts C, Marton MJ, Parrish M, Atsma D, Witteveen A, Glas A, Delahaye L, van der Velde T, Bartelink H, Rodenhuis S, Rutgers ET, Friend SH, Bernards R. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002 Dec 19;347(25):1999-2009. doi: 10.1056/NEJMoa021967.

Results Reference

background

PubMed Identifier

16977338

Citation

Zitvogel L, Tesniere A, Kroemer G. Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat Rev Immunol. 2006 Oct;6(10):715-27. doi: 10.1038/nri1936. Epub 2006 Sep 15.

Results Reference

background

PubMed Identifier

15776005

Citation

Zou W. Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer. 2005 Apr;5(4):263-74. doi: 10.1038/nrc1586.

Results Reference

background

PubMed Identifier

17187072

Citation

Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini JL, Castedo M, Mignot G, Panaretakis T, Casares N, Metivier D, Larochette N, van Endert P, Ciccosanti F, Piacentini M, Zitvogel L, Kroemer G. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med. 2007 Jan;13(1):54-61. doi: 10.1038/nm1523. Epub 2006 Dec 24.

Results Reference

background

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

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