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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Centre Leon Berard
ClinicalTrials.gov Identifier:
NCT01440413
First received: September 14, 2011
Last updated: October 29, 2014
Last verified: October 2014
  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:


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:
    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).

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
France
Centre Georges François Leclerc
DIJON Cedex, France, 21079
Centre Leon Berard
LYON Cedex 08, France, 69373
Sponsors and Collaborators
Centre Leon Berard
Investigators
Principal Investigator: Olivier TREDAN, MD Centre Leon Berard
  More Information

Publications:

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: October 29, 2014
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
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases

ClinicalTrials.gov processed this record on November 25, 2014