Enzalutamide and Paclitaxel Before Surgery in Treating Patients With Stage I-III Androgen Receptor-Positive Triple-Negative Breast Cancer
Enzalutamide and Paclitaxel Before Surgery in Treating Patients With Stage I-III Androgen Receptor-Positive Triple-Negative Breast Cancer
This phase IIB trial studies how well enzalutamide and paclitaxel before surgery works in
 treating patients with stage I-III androgen receptor-positive triple-negative breast cancer.
 Androgens can cause the growth of triple-negative breast cancer. Anti-hormone therapy, such
 as enzalutamide, prevent androgen from binding to the androgen receptor, thereby decreasing
 cell growth and causing tumor cell death. Drugs used in chemotherapy, such as paclitaxel,
 work in different ways to stop the growth of tumor cells, either by killing the cells, by
 stopping them from dividing, or by stopping them from spreading. Giving enzalutamide and
 paclitaxel before surgery may make the tumor smaller and reduce the amount of normal tissue
 that needs to be removed. This treatment study is part of the MD Anderson Moonshot
 initiative.
PRIMARY OBJECTIVES:

 I. To evaluate the pathologic complete response (pCR) and residual cancer burden-index
 (RCB-I) rates of patients with triple-negative breast cancer (TNBC) who were non-responders
 to initial anthracycline and cyclophosphamide chemotherapy and who were treated with
 enzalutamide in combination with weekly paclitaxel in the neoadjuvant setting.

 SECONDARY OBJECTIVES:

 I. To estimate progression free survival (PFS) distribution of androgen receptor
 (AR)-positive TNBC patients who were nonresponders to initial anthracycline and
 cyclophosphamide chemotherapy, treated with enzalutamide in combination with weekly
 paclitaxel in the neoadjuvant setting.

 II. To determine the safety of administering enzalutamide in combination with weekly
 paclitaxel.

 EXPLORATORY OBJECTIVES:

 I. To investigate the association between biomarkers in the peripheral blood and tumor tissue
 with safety and efficacy for TNBC patients who were treated with enzalutamide and treatment
 in combination with weekly paclitaxel in the neoadjuvant setting.

 II. To investigate the correlation between circulating tumor cells (CTC) characteristics
 and/or gene profiles and treatment response of enzalutamide and taxane.

 OUTLINE:

 Patients receive enzalutamide orally (PO) daily on days 1-7 and paclitaxel intravenously (IV)
 over 2 hours on day 1. Cycles repeat every 7 days for up to 12 cycles in the absence of
 disease progression or unacceptable toxicity.

 SURGERY: After 12 cycles of therapy, patients undergo surgical resection of primary tumor
 with or without lymph node biopsy or complete axillary dissection.

 After completion of study treatment, patients are followed up within 30 days after surgery.
Inclusion Criteria:

 -  Patients must be willing to sign the protocol-specific written informed consent

 -  Patients with histologically confirmed intact primary cancer that is confirmed
 invasive carcinoma of the breast, with at least 1.0 cm residual disease as measured by
 mammography, ultrasound, or breast magnetic resonance imaging (MRI) after neoadjuvant
 anthracycline based chemotherapy

 -  Patients must have triple-negative breast cancer defined as estrogen receptor (ER) <
 10%; progesterone receptor (PR) < 10% by immunohistochemistry (IHC) and human
 epidermal growth factor receptor 2 (HER2) 0-1+ by IHC or 2+, fluorescence in situ
 hybridization (FISH) non-amplified

 -  Androgen receptor will be quantified using a Clinical Laboratory Improvement Act
 (CLIA)-compliant assay for AR on a biopsy specimen obtained prior to the start of
 treatment; AR-positivity is defined as >= 10% of nuclear staining

 -  Patient's disease state must be American Joint Committee on Cancer (AJCC) 7th edition
 stage I-III

 -  Patients must have a performance status of 0 - 1 on the Eastern Cooperative Oncology
 Group (ECOG) performance scale

 -  A negative serum or urine pregnancy test must be done within 72 hours before the first
 dose of the study medication for women of childbearing potential as per institutional
 guidelines; post-menopausal women (defines as no menses for at least 1 year) and
 surgically sterilized women are not required to undergo pregnancy test

 -  Men on study must use a condom if having sex with a pregnant woman

 -  Male patients and his female partner who is of childbearing potential must use 2
 acceptable methods of birth control (one of which must include a condom as a barrier
 method of contraception) starting at screening and continuing throughout the study
 period and for 3 months after final study drug administration

 -  Absolute neutrophil count >= to 1,500 /uL

 -  Platelets >= to 100,000 /uL

 -  Hemoglobin >= to 9 g/dL

 -  Creatinine clearance >= to 50 ml/min

 -  Total bilirubin =< to 1.5 X upper limit of normal (ULN)

 -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< to 2.5 X ULN

 Exclusion Criteria:

 -  Patients who have received any other previous antitumor therapies (other than
 anthracycline-based neoadjuvant chemotherapy for the current cancer event)

 -  Breast-feeding at screening or planning to become pregnant during the course of
 therapy

 -  Patients who have had major surgery within 21 days before cycle 1, day 1

 -  Patients with known history of hypersensitivity to paclitaxel that did not resolve
 with pre-medication

 -  Patients with left ventricular ejection fraction < 50% or 10% decrease from baseline
 on echocardiogram after anthracycline based chemotherapy

 -  Patients with gastrointestinal impairment that would affect the absorption of
 enzalutamide or previous history of colitis

 -  Subjects requiring daily corticosteroids, other than those given as premedication for
 the anthracycline-based chemotherapy

 -  Patients with known or suspected brain metastasis or active leptomeningeal disease

 -  History of seizure or any condition that may predispose to seizure (e.g., prior
 cortical stroke, significant brain trauma) at any time in the past; also, history of
 loss of consciousness or transient ischemic attack within 12 months of day 1 visit

 -  Myocardial infarction within 6 months before starting therapy, symptomatic congestive
 heart failure (New York Heart Association > class II), unstable angina, or unstable
 cardiac arrhythmia requiring medication