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

NCT02689427 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2015-0488NCI-2016-00367
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

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.

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; Stage IIIC Breast Cancer AJCC v7; Triple-Negative Breast Carcinoma

Keywords

Androgen Receptor positive TNBC

Outcome Measures

Primary Outcomes (2)

• RCB Status

  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)

  4 years

• Incidence of Residual Cancer Burden-index

  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.

  Up to 30 days after surgery

Secondary Outcomes (1)

• Progression-free Survival Distribution

  From enrollment to progression of disease or death whichever comes first, up to 30 days after surgery

Other Outcomes (1)

• Levels of Biomarkers of Response

  Up to 30 days after surgery

Study Arms (1)

Treatment (enzalutamide, paclitaxel)

EXPERIMENTAL

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; Drug: Enzalutamide; Other: Laboratory Biomarker Analysis; Procedure: Lymph Node Biopsy; Drug: Paclitaxel; Procedure: Therapeutic Conventional Surgery

Interventions

Axillary Lymph Node Dissection PROCEDURE

Undergo axillary lymph node dissection

Also known as: ALND, Axillary Dissection, Axillary Lymphadenectomy, Axillary Node Dissection, Excision Axillary Lymph Nodes

Treatment (enzalutamide, paclitaxel)

Enzalutamide DRUG

Given PO

Also known as: ASP9785, MDV3100, Xtandi

Treatment (enzalutamide, paclitaxel)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (enzalutamide, paclitaxel)

Lymph Node Biopsy PROCEDURE

Undergo lymph node biopsy

Also known as: Biopsy of Lymph Node

Treatment (enzalutamide, paclitaxel)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Treatment (enzalutamide, paclitaxel)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgical resection of primary tumor

Treatment (enzalutamide, paclitaxel)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 MRI after neoadjuvant anthracycline based chemotherapy.
• Triple-negative breast cancer defined as ER\<10%; PR\<10% by immunohistochemistry (IHC) and HER2 0-1+ by IHC, or 2+ FISH non-amplified.
• 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.
• AJCC 7th edition stage I-III Breast Cancer
• Men or women 18 years of age or older.
• Patients must have a performance status of (0-1) on the 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 (defined 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 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
• 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

You may not qualify if:

• Patients who have received any previous antitumor therapies (other than anthracyclinebased 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 having 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MD Anderson West Houston

Houston, Texas, 77079, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

enzalutamide; Sentinel Lymph Node Biopsy; Paclitaxel; Taxes

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Lymph Node Excision; Investigative Techniques; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Results Point of Contact

• Title: Clinton Yam, MD
• Organization: The University of Texas MD Anderson Cancer Center

cyam@mdanderson.org

(832) 589-8343

Study Officials

• Clinton Yam

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2016
• First Posted: February 24, 2016
• Study Start: September 22, 2016
• Primary Completion: November 15, 2023
• Study Completion: November 15, 2023
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-07

Locations

US (2)