AR-inhibitor Bicalutamide in Treating Patients With TNBC (Arbre)
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|ClinicalTrials.gov Identifier: NCT02353988|
Recruitment Status : Unknown
Verified January 2015 by Xiaoxiang Guan, Jinling Hospital, China.
Recruitment status was: Not yet recruiting
First Posted : February 3, 2015
Last Update Posted : February 3, 2015
|Condition or disease||Intervention/treatment||Phase|
|Breast Neoplasms||Drug: Bicalutamide Other: Physician's Choice||Phase 2|
More than 70% of human breast cancers express the androgen receptor (AR), and in retrospective analysis, the expression of AR in Triple-Negative Breast Cancer (TNBC) varies from 10-43%. Recently emerging preclinical and clinical data suggest that AR may play a role in tumor proliferation. For example, Hu et al (2011) analyzed AR expression in 211 TNBC cases. He found that AR is related with an 83% increase in overall mortality, when compared with AR-negative TNBC. McGhan et al (2014) also found that AR expression tends to exist in TNBC patients with higher tumor stage and lymph metastases.
The role of AR has also been extensively studied in vitro. With targeting AR with small interfering RNA (siRNA) and treatment with anti-androgen bicalutamide, studies showed that AR has a proliferative role in TNBC cells. Robinson et al (2011) also clarified that AR can mimic estrogen receptor α (ERα) in a transcriptionally active manner directed by the forkhead box protein A1 (FoxA1). These indicate that, in ER-negative disease, AR can promote tumor progression, therefore, could serve as a therapeutic target in TNBC.
Due to the demonstration of oncogenic role for the AR in TNBC, clinical trials are underway to study the role of inhibiting androgen signaling for the treatment for TNBC. For example, Gucalp et al (2013) performed a sing-arm phase II study to investigate the role of bicalutamide in AR-positive TNBC. A total of 26 patients were enrolled in the study, and the study demonstrated a general well tolerated effect and a 6-month clinical benefit rate of 19%. Furthermore, future clinical trials are also designed to show the anti-androgen therapy such as Enzalutamide, the 17alpha-hydroxylase/C(17,20)-lyase inhibitor abiraterone acetate and orteronel for AR-positive TNBC. This study is investigated to study the role of bicalutamide for AR-positive TNBC, and it may help clarify the effect of bicalutamide for the specific breast cancer subtype. Furthermore, it may provide an additional therapy to treat the difficult to treat population.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Bicalutamide in Treating Patients With AR-positive Metastatic Triple Negative Breast Cancer|
|Study Start Date :||January 2015|
|Estimated Primary Completion Date :||January 2017|
|Estimated Study Completion Date :||May 2017|
This is a multi-center, open-label, phase II study to evaluate the anti-tumor activity and safety of bicalutamide administered orally daily to patients with estrogen receptor (ER)-negative/ progesterone receptor (PgR)-negative/ androgen receptor (AR)-positive metastatic breast cancer. Eligible patients will receive bicalutamide at a dose of 150mg PO daily.
Patients in experimental group are designated to take bicalutamide orally, 150mg on a continuous schedule. The investigator should pay attention to the patients' adverse event. Every month, the patients will be evaluated for the adverse event by the criterion National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3.0. Every 2 months, the patients will be evaluated for the clinical effects. If disease progressed, the patients would be ruled out.
Treatment continued until disease progression, unacceptable toxic effects, patient or physician request to discontinue, or serious protocol non-compliance. A maximum of 2 dose reductions for grade >= 3 toxicity were allowed (100 and 50 mg). A maximum of 2 weeks was permitted for treatment delays due to toxicity.
Other Name: immunohistochemistry staining method
Active Comparator: Physician's Choice
Treatment of the Physician's Choice defined as any single agent chemotherapy, hormonal treatment or biological therapy approved for the treatment of cancer; or palliative treatment or radiotherapy, administered according to local practice, if applicable
Other: Physician's Choice
The comparator group, treatment of physician's choice (TPC), represented a mix of agents (both approved and non-approved for metastatic breast cancer) to mirror clinical practice at the time in this setting.
The 60 patients are enrolled in the study, before randomized to the two arms, each of them will be assessed for eligibility and then their proposed TPC.
Treatment continued until disease progression, unacceptable toxic effects, patient or physician request to discontinue, or serious protocol non-compliance.
- Clinical benefit rate(CBR) [ Time Frame: 1 Year ]The proportion of stability, partial response and complete response in patients who receive bicalutamide as second-, or third-line therapy for estrogen receptor (ER)/ progesterone receptor (PgR)-negative, human epidermal growth factor receptor (HER-2)-negative and AR-positive Metastatic Breast Cancer
- Progression-free survival [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months ]
- Quality of life [ Time Frame: 1 Year ]FACT(Functional Assessment of Cancer Therapy) -B :a 36-item compilation, subdivided into four primary QOL (Quality of life) domains and a disease specific domain - additional concerns for breast cancer
- Number of adverse events (AE) and serious adverse events (SAE) during the course of the study [ Time Frame: 1 Year ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02353988
|Contact: Xiaoxiang Guan, MD; PhD||+86 email@example.com|