Bicalutamide Plus Aromatase Inhibitors in ER(+)/AR(+)/HER2(-) Metastatic Breast Cancer

Study Overview
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Brief Summary
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This study is aim to evaluate the efficacy and safety of bicalutamide and aromatase inhibitor in ER(+)/AR(+)/HER2(-) metastatic breast cancer patients who have disease progression after treatment of an aromatase inhibitor.

Detailed Description
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Androgen receptor(AR) is closely related to molecular type, treatment and prognosis in breast cancer. Over 70% of breast cancer expressed androgen receptor. And in some estrogen receptor positive breast cancer cells which are resistant to Aromatase inhibitors can change androgen receptor dependent. So AR may be a new target in the treatment of breast cancer. Bicalutamide is a selective androgen receptor inhibitor with a clinical benefit rate of 19% and median progression free survival of 12 weeks in the ER-/AR+ metastatic breast cancer. This study is aim to evaluate the efficacy and safety of bicalutamide and aromatase inhibitor in ER+/AR+/HER- metastatic breast cancer patients who have disease progression after treatment of an AI.

Official Title
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A Phase II Study of the Efficacy and Tolerability of Bicalutamide Plus Aromatase Inhibitors in Estrogen Receptor(+)/Androgen Receptor(+)/HER2(-) Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Bicalutamide
* Drug: Aromatase Inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically confirmed estrogen receptor positive, androgen positive and HER2 negative breast cancer Metastatic or unresectable locally advanced disease Age over 18 years Postmenopausal status （continuous using luteinizing hormone releasing hormone(LHRH) analogue is available） Patient must have disease progression after treatment of an Aromatase inhibitor. Eastern Cooperative Oncology Group (ECOG) performance status (PS)0-2 Life expectancy over 3 months. Measurable disease according to RECIST version 1.1 or only bone metastasis Adequate hematological, hepatic function. Voluntarily signed and dated written informed consent prior to any study specific procedure. Exclusion Criteria: Patient with life-threatening visceral metastasis, such as extensive liver metastasis, brain or meningeal metastasis Concomitant diseases/conditions that is not controllable, and Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study. History of other primary malignancy Resistant to steroidal or nonsteroidal aromatase Inhibitor

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: bicalutamide+ Aromatase Inhibitor<br>ER(+)/AR(+)/HER2(+) metastatic breast cancer patients that previously treated by an aromatase inhibitor | Drug: Bicalutamide<br>* 50mg once a day orally<br>* Other names: Casodex;Drug: Aromatase Inhibitor<br>* participants will receive any kind of aromatase inhibitor which has not been received before (steroidal AI change to nonsteroidal AI and vice versa), Letrozole 2.5mg once a day orally, Anastrozole 1mg once a day orally, Exemestane 25mg once a day orally<br>* Other names: exemestane;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical benefit rate（CBR） | Response and progression will be evaluated using RECIST 1.1. Evaluation will occur every 2 months for the first 6 months and then every 3 months till progression or termination of the study.CBR is defined as ratio of participants who have stable disease for over 24 weeks. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival | Time from to the first documentation of objective tumor progression or to death due to any cause. | baseline up to approximately 6 months | 
| objective response rate of bicalutamide plus another AI in participants with measurable disease | objective response rate includes complete response, partial response. | 24 weeks | 
| tolerability of bicalutamide plus an Aromatase inhibitor | evaluate and quality of life of the participants using Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) . | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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androgen receptor, bicalutamide, aromatase inhibitors, advanced breast cancer, letrozole, anastrozole, exemestane