Enzalutamide and Paclitaxel Before Surgery in Treating Patients With Stage I-III Androgen Receptor-Positive Triple-Negative Breast Cancer

Sponsor

M.D. Anderson Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT02689427

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

69.2

Anticipated Duration (Months)

18.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Invasive Breast Carcinoma Stage I Breast Cancer AJCC v7 Stage IA Breast Cancer AJCC v7 Stage IB Breast Cancer AJCC v7 Stage II Breast Cancer AJCC v6 and v7 Stage IIA Breast Cancer AJCC v6 and v7 Stage IIB Breast Cancer AJCC v6 and v7 Stage III Breast Cancer AJCC v7 Stage IIIA Breast Cancer AJCC v7 Stage IIIB Breast Cancer AJCC v7 Stage IIIC Breast Cancer AJCC v7 Triple-Negative Breast Carcinoma	Procedure: Axillary Lymph Node Dissection Drug: Enzalutamide Other: Laboratory Biomarker Analysis Procedure: Lymph Node Biopsy Drug: Paclitaxel Procedure: Therapeutic Conventional Surgery	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

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:

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

EXPLORATORY OBJECTIVES:

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.
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. Treatments 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

37 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase IIB Study of Neoadjuvant ZT Regimen (Enzalutamide Therapy in Combination With Weekly Paclitaxel) for Androgen Receptor (AR)-Positive Triple-Negative Breast Cancer

Actual Study Start Date :

Sep 22, 2016

Anticipated Primary Completion Date :

Jun 30, 2022

Anticipated Study Completion Date :

Jun 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (enzalutamide, paclitaxel) Patients receive enzalutamide PO daily on days 1-7 and paclitaxel IV over 2 hours on day 1. Treatments 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.	Procedure: Axillary Lymph Node Dissection Undergo axillary lymph node dissection Other Names: ALND Axillary Dissection Axillary Lymphadenectomy Axillary Node Dissection Excision Axillary Lymph Nodes Drug: Enzalutamide Given PO Other Names: ASP9785 MDV3100 Xtandi Other: Laboratory Biomarker Analysis Correlative studies Procedure: Lymph Node Biopsy Undergo lymph node biopsy Other Names: Biopsy of Lymph Node Drug: Paclitaxel Given IV Other Names: Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat Procedure: Therapeutic Conventional Surgery Undergo surgical resection of primary tumor

Arm

Intervention/Treatment

Experimental: Treatment (enzalutamide, paclitaxel)

Patients receive enzalutamide PO daily on days 1-7 and paclitaxel IV over 2 hours on day 1. Treatments 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.

Procedure: Axillary Lymph Node Dissection

Undergo axillary lymph node dissection

Other Names:

ALND

Axillary Dissection

Axillary Lymphadenectomy

Axillary Node Dissection

Excision Axillary Lymph Nodes

Drug: Enzalutamide

Given PO

Other Names:

ASP9785

MDV3100

Xtandi

Other: Laboratory Biomarker Analysis

Correlative studies

Procedure: Lymph Node Biopsy

Undergo lymph node biopsy

Other Names:

Biopsy of Lymph Node

Drug: Paclitaxel

Given IV

Other Names:

Anzatax

Asotax

Bristaxol

Praxel

Taxol

Taxol Konzentrat

Procedure: Therapeutic Conventional Surgery

Undergo surgical resection of primary tumor

Outcome Measures

Primary Outcome Measures

Incidence of pathologic complete response (residual cancer burden-zero) and residual cancer burden-index [Up to 30 days after surgery]
Using a Simon optimal two-stage design with alpha = beta = 10%, and then setting the threshold for an acceptable pathologic complete response or residual cancer burden-index rate at 20%. Will be estimated by the proportion of patients with pathologic complete response (residual cancer burden-zero) or residual cancer burden-index as the response rate along with an appropriate 95% confidence interval.
Incidence of residual cancer burden-index [Up to 30 days after surgery]
Using a Simon optimal two-stage design with alpha = beta = 10%, and then setting the threshold for an acceptable pathologic complete response or residual cancer burden-index rate at 20%. Will be estimated by the proportion of patients with pathologic complete response (residual cancer burden-zero) or residual cancer burden-index as the response rate along with an appropriate 95% confidence interval.

Secondary Outcome Measures

Progression-free survival distribution [From enrollment to progression of disease or death whichever comes first, up to 30 days after surgery]
Estimated using Kaplan-Meier method. Progression of disease defined as > 20% increase in tumor.

Other Outcome Measures

Levels of biomarkers of response [Up to 30 days after surgery]
Correlated with pathologic response to treatment using appropriate statistical analyses for the biomarker of interest.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Signed 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
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
American Joint Committee on Cancer (AJCC) 7th edition stage I-III breast cancer
Patients must have a performance status of 0 - 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
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 >= 100,000 /uL
Hemoglobin >= 9 g/dL
Creatinine clearance >= 50 ml/min
Total bilirubin =< 1.5 X upper limit of normal (ULN)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 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)
Female patients must not be 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