Study of the Impact of Everolimus Treatment on Lymphocytes NK (Natural Killer) Development and Functions for Patients With a Metastatic Breast Cancer (HR+ / HER2/Neu Negative)

Study Overview
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Brief Summary
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NK (Natural Killer) cells are important in the fight against tumor, especially for the control of cancer metastasis. The purpose of this prospective study is to evaluate the impact on lymphocytes NK functions and development of an everolimus treatment in women treated for a metastatic breast cancer. In particular, the study of lymphocytes NK functions and development under everolimus treatment could permit to validate an early biomarker of the impact of everolimus on these NK cells.

Official Title
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RAPANK: Study of the Impact of Everolimus Treatment on the Development and Functions of Lymphocytes NK (Natural Killer), for Patients With a Metastatic Breast Cancer (HR+ / HER2/Neu Negative)

Conditions
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Breast Cancer

Intervention / Treatment
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* Other: prospective study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women > 18 years old Metastatic breast cancer HR+ (Hormone Receptor positive), HER2/neu negative (Human Epidermal Growth Factor Receptor-2) ECOG PS (Eastern Cooperative Oncology Group Performance Status) ≤2 Eligible to an hormonotherapy treatment combined to an mTOR (mammalian Target Of Rapamycin) inhibitor (i.e. SPC (Summary of Product Characteristics) modalities) Measurable disease according to RECIST 1.1 (Response Evaluation Criteria In Solid Tumors) Not receiving the non-authorized concomitant treatments Patient should understand, sign, and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures performed. Patients must be covered by a medical insurance Exclusion Criteria: BMI>30 All dysimmune disease, history of transplantation or immunosuppressive therapy or corticotherapy All chronic inflammatory diseases Last chemotherapy < 6 months Corticotherapy <1 year and more than 1 month Restrictive diet ≤3 months before inclusion

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Everolimus<br>Immunomonitoring | Other: prospective study<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure of the level of Granzyme B (GzmB) |  | Timepoint at 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | The objective response rate (ORR) will be defined as the proportion of patients (described on the efficacy-evaluable population) who achieve complete response (CR) or partial response (PR). ORR is based on tumor assessments (measurements according to RECIST 1.1 | 12 months | 
| Progression-Free Survival (PFS) | Measured from the date of study drugs start to the date of the first objective radiological disease progression using RECIST 1.1 or death. | 12 months | 
| Overall Survival (OS) | Defined as the duration of time from start of treatment to time of death. | 12 months | 
| Intercurrent diseases reporting | Number of patients with adverse events (including infectious events) related to everolimus | 12 months | 
| Circulating NK functions | Characterization of circulating NK functions by flow cytometry | Timepoint at 3 months and at 9 months | 
| mTOR activation status | rpS6 phosphorylation rate by western blot | Timepoint at 3 months and at 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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everolimus, NK, metastatic