Bicalutamide as A Treatment in AR-positive Metastatic Triple-Negative Breast Cancer (mTNBC) Patients

Study Overview
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Brief Summary
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This prospective, single center, phase II study is to evaluate the efficacy and safety of bicalutamide as a treatment in androgen receptor (AR)-positive metastatic triple-negative breast cancer (mTNBC) patients.

Detailed Description
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Triple-negative breast cancer (TNBC) is defined as the absence of estrogen and progesterone receptor expression as well as ERBB2 amplification. It has no response to endocrine or anti-ERBB2 therapies. Recent studies have found some potential therapeutic targets for TNBC. However, it still has a poor outcome. It was reported that TNBC has six subtypes, including 2 basal-like (BL1 and BL2), an immunomodulatory (IM), a mesenchymal (M), a mesenchymal stem-like (MSL), and a luminal androgen receptor (LAR) subtype. Different subtype may be sensitive to different treatment. Bicalutamide is an oral, non-steroidal, androgen receptor (AR) antagonist. It is approved by the Food and Drug Administration (FDA) for the treatment of metastatic prostate cancer. Recently, a study explored the efficacy of bicalutamide in AR positive, estrogen receptor negative metastatic breast cancer (MBC), which showed a high clinical benefit rate (CBR) and a good safety profile. Based on the above reasons, we initiate this phase II study to evaluate the efficacy and safety of bicalutamide in AR positive metastatic triple-negative breast cancer patients.

Official Title
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A Prospective, Single Center, Phase II Study of Bicalutamide as A Treatment in Androgen Receptor (AR)-Positive Metastatic Triple-Negative Breast Cancer (mTNBC) Patients

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Bicalutamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females elder than 18 Histological proven unresectable or metastatic breast cancer patients who underwent at least one chemotherapy regimen for metastatic disease Patients with androgen Receptor (AR) positive (IHC >10% nuclear staining) either for primary tumor or metastatic lesion Triple-negative for estrogen receptor (ER), progestogen receptor (PR), and human epithelial receptor-2 (HER2) by IHC (ER <1%, PR <1% and Her2 negative). A negative Her2 gene amplification should be verified by FISH test for those patients with Her2 (2+). For those with Her2 (1+), FISH test might be considered by the investigator. At least one measurable disease according to the response evaluation criteria in solid tumor (RECIST 1.1) Performance status no more than 2 All patients enrolled are required to have adequate hematologic, hepatic, and renal function Life expectancy longer than 12 weeks No serious medical history of heart, lung, liver and kidney Be able to understand the study procedures and sign informed consent. Patients with good compliance Exclusion Criteria: Pregnant or lactating women Women of child-bearing potential, unwilling to use adequate contraceptive protection during the process of the study Patients treated with an investigational product within 4 weeks before the enrollment Patients who received chemotherapy within 4 weeks before the enrollment Patients with symptomatic central nervous system metastases are not permitted, except for those with stable and asymptomatic brain metastases who have completed cranial irradiation, and have at least one measurable lesion outside the brain. Radiotherapy should be completed within 4 weeks prior to the registration Other active malignancies (including other hematologic malignancies) or other malignancies within the last 5 years, except for cured nonmelanoma skin cancer or cervical intraepithelial neoplasia. Patients having a history of clinically significant cardiovascular, hepatic, respiratory or renal diseases, clinically significant hematological and endocrinal abnormalities, clinically significant neurological or psychiatric conditions Uncontrolled serious infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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<br>150mg, po, qd, d1-28 | Drug: Bicalutamide<br>* 150mg, po, qd, d1-28<br>* Other names: Casodex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical benefit rate (CBR) | Clinical benefit rate is defined as the percentage of patients who achieve complete response (CR), partial response (PR) and stable disease (SD) ≥24 weeks by RECIST version 1.1 criteria. | every 8 weeks, up to 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Objective response rate is defined as the percentage of patients who achieve complete response (CR) and partial response (PR) by RECIST version 1.1 criteria. | every 8 weeks, up to 24 weeks | 
| Progression free survival (PFS) | Progression free survival is defined as the time from enrollment to the first documented disease progression or death from any cause. | every 8 weeks, up to 48 months | 
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | Evaluate incidence of adverse events and severity grade of these events | every 4 weeks, up to 24 weeks | 
| Overall Survival (OS) | Overall Survival is defined as the time from enrollment to death from any cause. | every 3 months, up to 100 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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triple negative breast cancer, androgen receptor, bicalutamide