A Study of Everolimus Plus Exemestane in Chinese Postmenopausal Women With Estrogen Receptor Positive, Locally Advanced, Recurrent, or Metastatic Breast Cancer After Recurrence or Progression on Non-steroidal Aromatase Inhibitor

Study Overview
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Brief Summary
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This study aims at evaluating the safety and efficacy of everolimus plus exemestane in Chinese postmenopausal women with ER+ HER2- ABC after recurrence or progression on letrozole or anastrozole. The rationale of this study is based on the following: Proven everolimus activity in breast cancer in combination with exemestane Efficacy and manageable safety profile of everolimus in combination with exemestane in the Asian subpopulation of BOLERO-2

Official Title
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A Randomized, Double-blind, Placebo Controlled, Phase II Study of Everolimus in Combination With Exemestane in the Treatment of Chinese Postmenopausal Women With Estrogen Receptor Positive, HER-2 Negative, Locally Advanced, Recurrent, or Metastatic Breast Cancer After Recurrence or Progression on Prior Letrozole or Anastrozole

Conditions
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Advanced Breast Cancer

Intervention / Treatment
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* Drug: Everolimus
* Drug: Exemestane
* Drug: Everolimus Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: locally advanced, recurrent, or metastatic breast cancer. Locally advanced breast cancer must not be amenable to curative treatment by surgery or radiotherapy. Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer Postmenopausal women. Postmenopausal status is defined either by: Prior bilateral oophorectomy Or age ≥60 Or age < 60 and amenorrhea for 12 or more months Recurrence or progression on prior NSAI is defined as: Recurrence while on, or within one year (12 months) of end of adjuvant treatment with letrozole or anastrozole OR Progression while on or within one month (30 days) of the end of prior treatment with letrozole or anastrozole Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to enrollment Patient must have as per RECIST 1.1 • measurable disease or non-measurable lytic or mixed (lytic + blastic) bone lesions in the absence of measurable disease. 8. Patient is able to swallow and retain oral medication 9. Patient must meet the hematologic & biochemistery laboratory values at the screening visit: Written informed consent must be obtained prior to any screening procedures Exclusion Criteria: Patients eligible for this study must not meet any of the following criteria: HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive), based on the most recent test. Note: Patients with IHC 2+ must have a negative in situ hybridization test. Patients who received more than one chemotherapy line for ABC Patient with symptomatic visceral disease and is candidate to chemotherapy Patients with only non-measurable lesions other than lytic or mixed (lytic and blastic) bone metastasis (e.g. pleural effusion, ascites etc.) Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use at the time of study entry except topical applications, inhaled sprays, eye drops or local injections. Uncontrolled diabetes mellitus as defined by HbA1c >7% despite adequate therapy. Other protocol-defined inclusion/exclusion criteria may apply

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: this is a double-blind, randomized, placebo-controlled study, parallel groups,
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Everolimus + Exemestane<br>Everolimus 10mg/Day + Exemestane 25mg/Day | Drug: Everolimus<br>* Everolimus was formulated as tablets of 5-mg strength and was packaged into blister packs . Everolimus (two 5 mg tablets daily) are administered in a blinded manner on their respective treatment arms by continuous oral daily dosing.<br>* Other names: RAD001;Drug: Exemestane<br>* Exemestane 25 mg orally daily.<br>|
| Active Comparator: Placebo + Exemestane<br>Placebo of everolimus in combination with exemestane 25 mg daily | Drug: Exemestane<br>* Exemestane 25 mg orally daily.<br>Drug: Everolimus Placebo<br>* Placebo was formulated to be indistinguishable from the everolimus tablets. Matching placebo (two tablets daily) are administered in a blinded manner on their respective treatment arms by continuous oral daily dosing.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | Progression-free Survival (PFS) Based on Local Radiology Review of Tumor Assessments. PFS will be analyzed when approximately 110 events are reached. | date of randomization to the date of the first documented progression or death from any cause which ever occur first, up to approximatly 19 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) assessed by Blinded Independent Review Committee (BIRC). | PFS in the two treatment arms as determined by a Blinded Independent Review Committee (BIRC). | date of randomization to the date of the first documented progression or death from any cause which ever occur first, up to approximatly 19 months. | 
| Overall survival | Overall survival (OS) in the two treatment arms | date of randomization to date of death up to approximately 19 months | 
| Overall response rate (ORR) | Overall response rate (ORR) defined as the proportion of patients with a best overall response defined as complete response (CR) or partial response (PR); (CR+PR). ORR will be analysed when approximatly 110 events are reached. | date of randomization to the date of the first documented progression or death from any cause which ever occur first, up to approximatly 19 months. | 
| Clinical benefit rate (CBR) | CBR, defined as the proportion of patients with best overall response of complete response (CR), partial response (PR) or stable disease (SD) with duration of 24 weeks or longer. CBR will be analyzed when approximately 110 events are reached. | date of randomization to the date of the first documented progression or death from any cause which ever occur first, up to approximatly 19 months | 
| Time to response | Time to response, defined as the time between date of randomization until first documented response (CR or PR). it will be analyzed when approximately 110 events are reached. | date of randomization to the date of the first documented progression or death from any cause which ever occur first, up to approximatly 19 months. | 
| Duration of Response DOR | DOR, defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to any cause | date of first documented CR or PR to date of first documented disease progression or death due to any cause up to apprximately 19 months | 
| ECOG | Time to deterioration of ECOG Performance Status | date of randomization up to approximately 19 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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everolimus, exemestane, advanced Breast Cancer, non-steroidal aromatase inhibitors, breast carcinoma, breast cancer, breast lump, HER2 negative, breast cancer progression