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

Phase 2

Completed

• Conditions: 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
• Interventions: Procedure: Axillary Lymph Node Dissection; Drug: Enzalutamide; Other: Laboratory Biomarker Analysis; Procedure: Lymph Node Biopsy; Drug: Paclitaxel; Procedure: Therapeutic Conventional Surgery

• Registration Number: NCT02689427
• Lead Sponsor: M.D. Anderson Cancer Center

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.

Detailed Description

PRIMARY OBJECTIVE:

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 in the neoadjuvant setting.

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. 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 Timeline

• Study First Submitted: 2016-02-12
• Study First Submitted QC: 2016-02-18
• Study First Posted: 2016-02-24
• Study Start: 2016-09-22
• Status Verified: 2023-11
• Primary Completion: 2023-11-15
• Study Completion: 2023-11-15
• Last Update Submitted: 2023-11-16
• Last Update Posted: 2023-11-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1. Signed written informed consent

2. 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 MRI after neoadjuvant anthracycline based chemotherapy.

3. Triple-negative breast cancer defined as ER<10%; PR<10% by immunohistochemistry (IHC) and HER2 0-1+ by IHC, or 2+ FISH non-amplified.

4. Androgen Receptor will be quantified using CLIA-compliant assays for AR on a biopsy specimen obtained prior to initiation of treatment.. AR-positivity is defined as > 10% of nuclear staining.

5. AJCC 7th edition stage I-III Breast Cancer

6. Men or women 18 years of age or older.

7. Patients must have a performance status of (0-1) on the ECOG performance scale

8. 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 (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo pregnancy test.

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

10. Male patient 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

11. Patient must have adequate organ function as determined by the following laboratory values:

    • Absolute neutrophil count ≥ 1,500 /μL
    • Platelets ≥ 100,000 / μL
    • Hemoglobin ≥ 9 g/dL
    • Creatinine Clearance > 50 ml/min
    • Total Bilirubin < 1.5 x ULN
    • ALT/AST < 2.5 x ULN

Exclusion Criteria

1. Patients who have received any previous antitumor therapies (other than anthracyclinebased neoadjuvant chemotherapy for the current cancer event).
2. Female patients must not be breast-feeding at screening or planning to become pregnant during the course of therapy.
3. Patients having major surgery within 21 days before Cycle 1, Day 1.
4. Patients with known history of hypersensitivity to paclitaxel that did not resolve with pre- medication.
5. Patients with left ventricular ejection fraction <50% or 10% decrease from baseline on echocardiogram after anthracycline based chemotherapy.
6. Patients with gastrointestinal impairment that would affect the absorption of Enzalutamide; or previous history of colitis.
7. Subjects requiring daily corticosteroids, other than those given as premedication for the anthracycline-based chemotherapy.
8. Patients with known or suspected brain metastasis or active leptomeningeal disease.
9. 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.
10. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (enzalutamide, paclitaxel)	Therapeutic Conventional Surgery	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.
Treatment (enzalutamide, paclitaxel)	Axillary Lymph Node Dissection	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.
Treatment (enzalutamide, paclitaxel)	Laboratory Biomarker Analysis	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.
Treatment (enzalutamide, paclitaxel)	Lymph Node Biopsy	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.
Treatment (enzalutamide, paclitaxel)	Enzalutamide	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.
Treatment (enzalutamide, paclitaxel)	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.

Primary Outcome Measures

Name	Time	Method
RCB Status	4 years	The RCB (Residual Cancer Burden) is a continuous variable derived from the primary tumor dimensions, cellularity of the tumor bed, and axillary nodal burden. RCB can be divided into four classes (RCB-0 to RCB-III) and will be collected as part of the study. RCB-0 (pCR), Minimal RCB (RCB-I), Moderate RCB (RCB-II), and Extensive RCB (RCB-III)
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

Name	Time	Method
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.

Trial Locations

Locations (2)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

MD Anderson West Houston; 🇺🇸 Houston, Texas, United States