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Trial record 85 of 1543 for:    Androgens

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

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ClinicalTrials.gov Identifier: NCT02689427
Recruitment Status : Recruiting
First Posted : February 24, 2016
Last Update Posted : June 7, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Astellas Pharma US, Inc.
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Androgen Receptor Positive Estrogen Receptor Negative HER2/Neu Negative Invasive Breast Carcinoma Progesterone Receptor Negative 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 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 37 participants
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 : September 22, 2016
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : September 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

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. 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.

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 Name: 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




Primary Outcome Measures :
  1. Incidence of pathologic complete response (residual cancer burden-zero) and residual cancer burden-index [ Time Frame: 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.

  2. Incidence of residual cancer burden-index [ Time Frame: 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 :
  1. Progression-free survival distribution [ Time Frame: 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:
  1. Levels of biomarkers of response [ Time Frame: Up to 30 days after surgery ]
    Correlated with pathologic response to treatment using appropriate statistical analyses for the biomarker of interest.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02689427


Contacts
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Contact: Naoto Ueno, MD, PHD 713-792-2817 nueno@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Naoto T. Ueno    713-792-2817      
Principal Investigator: Naoto T. Ueno         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Astellas Pharma US, Inc.
Investigators
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Principal Investigator: Naoto T Ueno M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02689427     History of Changes
Other Study ID Numbers: 2015-0488
NCI-2016-00367 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2015-0488 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: February 24, 2016    Key Record Dates
Last Update Posted: June 7, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by M.D. Anderson Cancer Center:
Androgen Receptor positive TNBC
Additional relevant MeSH terms:
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Androgens
Carcinoma
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs