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Modifications of Immune Microenvironment Induced by Neoadjuvant Chemotherapy in Triple-negative BC (MIMOSA)

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ClinicalTrials.gov Identifier: NCT04368468
Recruitment Status : Not yet recruiting
First Posted : April 29, 2020
Last Update Posted : April 29, 2020
Sponsor:
Information provided by (Responsible Party):
Institut Claudius Regaud

Brief Summary:

The prescription of neoadjuvant chemotherapy becomes a standard in women with HER2-positive or triple-negative breast cancer and allows a complete histological response (pCR) which represents a prognostic factor for survival. . The problem for patients who are not pCR is that they are currently receiving non-personalized adjuvant systemic treatment.

The identification of biomarkers present in the residual disease would be a criterion to guide the choice of post-neoadjuvant adjuvant systemic treatment, in order to personalize it.

At the present time, there is no published study describing extensively the immune micro-environment (ME) in breast cancer, whether before or after chemotherapy, nor its modification induced by chemotherapy.

The team therefore propose to study in a retrospective and monocentric series, the modifications of the immune ME induced by a "standard" neo-adjuvant chemotherapy in patients with triple-negative CS, whether they are in complete histological response or not (n = twice 50).

The main objective of this project is to describe the changes in the immune ME of triple-negative breast cancers induced by neoadjuvant chemotherapy for all patients (in pCR or not):

  • Quantification of TILs and subtypes of TILs (CD4 and CD8)
  • Expression of the three immune checkpoints that are PDL1, TIM3 and LAG3
  • Describe the organization of the immune system (immunostaining on the same slide of the PDL1, TIM3 and LAG3 immune checkpoints)

Condition or disease Intervention/treatment
Triple Negative Breast Cancer Other: biomarker evolution

Detailed Description:

Retrospective and monocentric translational study carried out on patients treated at the IUCT-Oncopole by neoadjuvant chemotherapy (sequential treatment FEC100 or EC100 then taxane, paclitaxel weekly for the most part) for a triple-negative CS between 2012 and 2018.

We have the microbiopsy of the primary tumor preserved in FFPE and the operating room preserved in FFPE.

We have all the clinical data for the diagnosis and monitoring of these patients, already entered into a database.

The search for a BRCA germline mutation is available in most patients if indicated for an oncogenetic consultation.

biomarkers analysis :

  • TILS account according to Salgado et al. before and after neoadjuvant chemotherapy
  • IHC CK5-6 and EGFR then RA if the first two are negative to characterize triple negative tumors in "basal-like" and "non-basal-like"
  • IHC CD3 (labeling of T lymphocytes)
  • IHC CD4, CD8 and FOXP3 before and after neoadjuvant chemotherapy
  • PDL1, TIM3 and LAG3 multiplex IHC before and after neoadjuvant chemotherapy
  • Labeling of tumor cells: AE1 / AE3
  • Use of markings for exploratory analyzes: CD68 (macrophages), CD39 (marker of lymphocyte exhaust

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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Study of the Modifications of the Immune Microenvironment Induced by Neoadjuvant Chemotherapy in Triple-negative Breast Cancers
Estimated Study Start Date : September 15, 2020
Estimated Primary Completion Date : September 15, 2021
Estimated Study Completion Date : December 15, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer


Intervention Details:
  • Other: biomarker evolution
    analysis of a list of biomarkers on triple negative breast tumors samples before and after neoadjuvant therapy
    Other Name: triple negative breast cancer biomarker evolution


Primary Outcome Measures :
  1. Identify Change of immune ME by TILS quantification of triple-negative breast cancer induced by neoadjuvant chemotherapy for all patients [ Time Frame: 12 months ]
    TILS ans substype quantification

  2. Identify Change of immune ME by PDL1 expression of triple-negative breast cancer induced by neoadjuvant chemotherapy for all patients [ Time Frame: 12 months ]
    expression of PDL1,

  3. Identify Change of immune ME by TIM3 expression of triple-negative breast cancer induced by neoadjuvant chemotherapy for all patients [ Time Frame: 12 months ]
    expression of TIM3

  4. Identify Change of immune ME by LAG3 expression of triple-negative breast cancer induced by neoadjuvant chemotherapy for all patients [ Time Frame: 12 months ]
    LAG3 expression


Secondary Outcome Measures :
  1. Compare change ofTILs quantification of triple-negative breast cancer induced by neoadjuvant chemotherapy for pCR patients and those not pCR and for subtype basal-like or not basal-like [ Time Frame: 12 months ]
    Quantification of TILs and subtypes TILs;

  2. Compare change of PDL1 expression of triple-negative breast cancer induced by neoadjuvant chemotherapy for pCR patients and those not pCR and for subtype basal-like or not basal-like [ Time Frame: 12 months ]
    expression of PDL1

  3. Compare change of TIM3 expression of triple-negative breast cancer induced by neoadjuvant chemotherapy for pCR patients and those not pCR and for subtype basal-like or not basal-like [ Time Frame: 12 months ]
    expression of TIM3

  4. Compare change of LAG3 expression of triple-negative breast cancer induced by neoadjuvant chemotherapy for pCR patients and those not pCR and for subtype basal-like or not basal-like [ Time Frame: 12 months ]
    expression of LAG3; organization of immune system

  5. determination of predictive factors of TILs quantification for response to neoadjuvant chemotherapy and disease free survival [ Time Frame: 12 months ]
    Correlation between TILs and TILs substypes quantification (on microbiopsy) and the histological response after neoadjuvant chemotherapy (pCR versus non pCR): determination of predictive factors for response to chemotherapy.

  6. determination of predictive factors of PDL1 expression for response to neoadjuvant chemotherapy and disease free survival [ Time Frame: 12 months ]
    Correlation between PDL1 expression on microbiopsy and the histological response after neoadjuvant chemotherapy (pCR versus non pCR): determination of predictive factors for response to chemotherapy.

  7. determination of predictive factors of TIM3 for response to neoadjuvant chemotherapy and disease free survival [ Time Frame: 12 months ]
    Correlation between TIM3 expression on microbiopsy and the histological response after neoadjuvant chemotherapy (pCR versus non pCR): determination of predictive factors for response to chemotherapy.

  8. determination of predictive factors of LAG3 for response to neoadjuvant chemotherapy and disease free survival [ Time Frame: 12 months ]
    Correlation between LAG3 expression on microbiopsy and the histological response after neoadjuvant chemotherapy (pCR versus non pCR): determination of predictive factors for response to chemotherapy.


Biospecimen Retention:   Samples With DNA
microbiopsy of the breast primary tumor preserved in FFPE and of the operative part preserved in FFPE.


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   female patients
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
100 samples
Criteria

Inclusion Criteria:

  • Samples from triple negative BC patients, patients treated by neoadjuvant chemotherapy ( FEC or EC than taxanes) Patients consent to use their samples.

Exclusion Criteria:

  • Samples not available before or after neoadjuvant chemotherapy
Publications of Results:

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Responsible Party: Institut Claudius Regaud
ClinicalTrials.gov Identifier: NCT04368468    
Other Study ID Numbers: 19HLSEIN02
First Posted: April 29, 2020    Key Record Dates
Last Update Posted: April 29, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Institut Claudius Regaud:
post neo adjuvant therapy
immune micro environment
biomerker chacterization
Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases