Molecular Alterations Associated With Resistance to Endocrine Therapy and Impacting Treatment With mTOR Inhibitor

Study Overview
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Brief Summary
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This is a prospective biomarker study to show that p4EBP1 staining predicts clinical benefit from treatment with everolimus in patients who are eligible for everolimus+exemestane treatment. This trial is not aimed at evaluating a drug activity. Everolimus and exemestane are prescribed within their approved indication as per usual practice and are not part of this trial.

Detailed Description
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Estrogen hormone receptor-positive metastatic breast cancer who failed to non steroidal aromatases inhibitors in patients who are eligible for everolimus+exemestane treatment

Official Title
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Identification of the Molecular Alterations Associated With Resistance to Endocrine Therapy and Impacting Treatment With mTOR Inhibitor of HR+ Metastatic Breast Cancer in Post-menopausal Women

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Procedure: Biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Eligible for everolimus+exemestane treatment as required by the marketing authorisation conditions Women (or men) with histologically-proven Estrogen Receptor-positive (ER+) and/or Progesterone Receptor-positive (PR+) / Human Epidermal growth factor Receptor 2-negative (HER2-) metastatic breast adenocarcinoma or locally advanced disease who cannot be treated with surgery and/or radiation therapy Postmenopausal women Asymptomatic if visceral disease Second line hormonotherapy or more for metastatic or locally advanced disease after recurrence or progression following a non-steroidal aromatase inhibitor (in adjuvant or metastatic setting) - Eligible for the biopsy Progressive disease under endocrine therapy at the time of inclusion Treatment with everolimus and exemestane not yet started Patients with metastases that can be biopsied, except bone metastases Measurable or evaluable disease Age ≥18 years WHO Performance Status 0/1 Provision of signed and dated, written informed consent prior to any protocol specific procedure, including biopsy Patient with social insurance coverage Exclusion Criteria: Contraindications for everolimus+exemestane treatment Previous treatment with an anti-mTOR therapy More than 1 previous line of chemotherapy in metastatic setting Life expectancy <3 months Spinal cord compression and/or symptomatic or progressive brain metastases (unless asymptomatic or treated and stable off steroids for at least 30 days prior to start of study drug) Haematopoietic function or organ impairment as shown by the following criteria: Polynuclear neutrophils <1.5 x 10⁹/L Platelets <100 x 10⁹/L Haemoglobin <90 g/L Alanine aminotransferase (ALAT) / aspartate aminotransferase (ASAT) >2.5 x ULN in the absence of or >5 x upper limit of normal (ULN) in the presence of liver metastases Bilirubin >1.5 x ULN Creatinine clearance ≤50 mL/min (measured or calculated by Cockcroft and Gault formula) Calcium and phosphate >ULN Abnormal coagulation or any other medical situation contraindicating biopsy Bone metastases when this is the only site of biopsiable disease Any condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol Individuals deprived of liberty or placed under the authority of a tutor

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Exemestane+everolimus<br>Exemestane+everolimus are administered as per their approved indication | Procedure: Biopsy<br>* biopsy of a metastasis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the predictive value of p4EBP1 for an mTOR inhibitor efficacy | The primary endpoint of the trial is the predictive value of p4EBP1 for an mTOR inhibitor efficacy, measured by the association between expression level of the biomarker (high vs low expression with a cutoff value set at the median percentages of marked cells) and clinical benefit after 6 months of everolimus+exemestane treatment. | from inclusion up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Failed non steroidal aromatases inhibitors, Eligible for everolimus+exemestane