NCT02353988

AR-inhibitor Bicalutamide in Treating Patients With TNBC

Bicalutamide in Treating Patients With AR-positive Metastatic Triple Negative Breast Cancer

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Jinling Hospital, China · Academic / Other
• Sex: Female
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Growing studies demonstrated that Androgen Receptor (AR) has an oncogenic role for the patients with AR-positive Triple Negative Breast Cancer (TNBC). AR antagonists in therapy, such as bicalutamide, completely binds to the AR, increasing AR degradation, thus are investigated for the efficacy of the treatment of patients with AR-positive TNBC in the study.

Detailed description

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.

Conditions

• Breast Neoplasms

Interventions

Type	Name	Description
DRUG	Bicalutamide	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	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.

Timeline

• Start date: 2015-01-01
• Primary completion: 2017-01-01
• Completion: 2017-05-01
• First posted: 2015-02-03
• Last updated: 2015-02-03