Relevance of T Lymphocytes Tumor Infiltrates CD8 and Foxp3 as Immune Prognostic Biomarker in Breast Cancer Treated by Neo Adjuvant Chemotherapy (PRIMUNEO)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Centre Georges Francois Leclerc
Sponsor:
Information provided by (Responsible Party):
Centre Georges Francois Leclerc
ClinicalTrials.gov Identifier:
NCT01513408
First received: January 17, 2012
Last updated: September 25, 2013
Last verified: September 2013
  Purpose

Neoadjuvant chemotherapy is standard therapy for the management of localised breast cancer, and makes it possible to evaluate tumour response. Achieving pathological complete response (pCR) after chemotherapy is the most important prognostic factor for these patients. However, patients with pCR can suffer relapse. In parallel, long-term prognosis of patients who do not achieve pCR is poorly documented, and no specific prognostic factors have been clearly identified.Preclinical and clinical studies argue for an immunogenic role of some chemotherapy regimens, such as anthracyclines, taxanes or trastuzumab. By facilitating recruitment of CD8 T-lymphocytes in the tumour bed, these agents could favourably influence antitumour immune response, partially contributing to efficacy. Conversely, tumours can promote accumulation of regulatory T-lymphocytes expressing Foxp3, thus evading anti-tumour immune response, and increased numbers of regulatory T-cells are associated with less favourable prognosis in breast cancer patients. We have previously shown that a high number of CD8 T-cells associated with low Foxp3 infiltration, as quantified by immunohistochemistry on surgical specimens, is associated with better response and better survival in breast cancer patients, independently of whether pCR was achieved, the type of chemotherapy used, and the type of breast cancer. Therefore, we propose to validate in a prospective study this immunological prognostic marker in a large cohort of patients treated with neoadjuvant chemotherapy.


Condition Intervention
Breast Cancer
Other: immunohistochemical detection of lymphocytes T CD8+/Foxp3 ratio

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Prospective Study of the Relevance of T Lymphocytes Tumor Infiltrates CD8 and Foxp3 as a New imMUne Prognostic Biomarker in Breast Cancer Treated by NEOadjuvant Chemotherapy

Resource links provided by NLM:


Further study details as provided by Centre Georges Francois Leclerc:

Primary Outcome Measures:
  • Overall survival [ Time Frame: From date of inclusion up to the end of follow-up period : december 2014 (anticipated) ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from inclusion date to death from any cause, or to date of last follow-up, if death does not occur.


Secondary Outcome Measures:
  • Recurrence-free survival [ Time Frame: From inclusion up to the end of follow up period: december 2014 ] [ Designated as safety issue: No ]
    Recurrence-free survival is defined as the time interval from the date of surgery to the date of first recurrence (loco-regional or metastatic) or to death (all causes). Patients alive without recurrence will be censored on the date of last follow-up.

  • Pathological complete response [ Time Frame: After surgery ] [ Designated as safety issue: No ]
    Pathological complete response on the surgically resected specimen is defined as the absence of any evidence of invasive carcinoma in the breast or dissected axillary lymph nodes.

  • PathIm score (pathological-immunological) [ Time Frame: From inclusion up to the end of surgery for all patients: december 2014 (anticipated) ] [ Designated as safety issue: No ]
    PathIm score (pathological-immunological)from 0 to 2, defining three patient groups with different prognoses (0 = good prognosis; 1 = intermediate prognosis; 2 = unfavourable prognosis), and defined as the sum of the pathology information regarding the extent of residual tumour according to the pAJCC score(pAJCC stage≤IIA = 0; pAJCC stage>IIA = 1), and the immunological information from the CD8/Foxp3 ratio (high CD8 AND low Foxp3 infiltration = 0, all other situations = 1)


Estimated Enrollment: 500
Study Start Date: May 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CD8/Foxp3
patient suffering from non-metastatic breast cancer
Other: immunohistochemical detection of lymphocytes T CD8+/Foxp3 ratio
For each patients included the study, a tumour block from the initial biopsy, as well as a representative block of residual tumour (area of complete tumoral regression, area of partial tumoral regression or area of unmodified residual tumour) will be chosen by the initial pathologist in each investigating centre. Once the pathologist has verified the concordance between the images observed on the blocks sent from the investigating centres, and the associated pathology reports, immunohistochemical analysis will be performed on the slides prepared from each block.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

inclusion criteria

  1. Signed informed consent
  2. Social security coverage
  3. Age between 18 and 80 years
  4. Histologically proven breast cancer, regardless of histological type or molecular subtype (triple negative, hormone-receptor positive, HER2+++), including inflammatory forms
  5. Localised breast cancer with or without axillary or subclavicular lymph node involvement
  6. Absence of bone or visceral metastasis on further evaluation (bone scintigraphy, chest X-ray, abdominal echocardiography or CT scan of the thorax, abdomen and pelvic area)
  7. Treatment by neoadjuvant chemotherapy (treatment protocol at physician's discretion)
  8. Patient amenable to receiving adjuvant therapy (chemotherapy, radiotherapy, hormone therapy, targeted therapy)
  9. Breast surgery (breast-sparing or not) planned after neoadjuvant chemotherapy

exclusion criteria

  1. Metastatic breast cancer
  2. Neoadjuvant radiotherapy
  3. Patient not amenable to surgery
  4. Ongoing therapy for any other type of cancer
  5. Legal incapacity (incarceration or persons under legal guardianship)
  6. Patient unable to sign the informed consent or unable to attend medical follow-up for geographical, social or mental reasons.
  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: NCT01513408

Contacts
Contact: Jérémy SKRZYPSKI, PHD 3 80 73 75 00 (3461) ext +33 jskrzypski@cgfl.fr
Contact: Sandrine TIAGO 3 45 34 80 51 ext +33 stiago@cgfl.fr

Locations
France
CGFL Recruiting
Dijon, France, 21079
Sponsors and Collaborators
Centre Georges Francois Leclerc
Investigators
Principal Investigator: Sylvain LADOIRE, MD Centre Georges Francois Leclerc
  More Information

No publications provided

Responsible Party: Centre Georges Francois Leclerc
ClinicalTrials.gov Identifier: NCT01513408     History of Changes
Other Study ID Numbers: 2011-1SLa-01
Study First Received: January 17, 2012
Last Updated: September 25, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Centre Georges Francois Leclerc:
breast cancer
CD8+
Foxp3
neoadjuvant chemotherapy

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on July 24, 2014