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Last Modified: 8/21/2008     First Published: 12/9/2005  
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Phase III Randomized Study of Neoadjuvant Therapy Comprising Exemestane Versus Letrozole Versus Anastrozole in Postmenopausal Women With Estrogen Receptor Positive Stage II or III Breast Cancer

Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Exemestane, Letrozole, or Anastrozole in Treating Postmenopausal Women Who Are Undergoing Surgery for Stage II or Stage III Breast Cancer

Basic Trial Information

Phase
Type
Status
Age
Sponsor
Protocol IDs

Phase III


Treatment


Active


Postmenopausal


NCI


ACOSOG-Z1031
CALGB-ACOSOG-Z1031, ACOSOG-Z1031, NCT00265759

Special Category: NCI Web site featured trial, CTSU trial

Objectives

Primary

  1. Determine whether anastrozole, exemestane, or letrozole administered for 16 to 18 weeks as neoadjuvant endocrine treatment for postmenopausal patients with stage II or stage III estrogen receptor-positive breast cancer should be chosen as the aromatase inhibitor arm of a future study that will compare neoadjuvant aromatase inhibitor treatment with neoadjuvant chemotherapy.

Secondary

  1. Compare the neoadjuvant treatment regimens relative to the rates of improvement in surgical outcome.
  2. Compare and confirm the radiological response rates (mammography and ultrasound by central radiological analysis) between these three neoadjuvant treatment regimens.
  3. Compare the relative safety of the neoadjuvant treatment regimens in terms of reported adverse events.
  4. Compare the tumor pathologic size between the neoadjuvant treatment regimens.
  5. Compare the rates of pathological complete response (defined as no invasive cancer in the post-treatment specimen).
  6. Compare the incidence of metastatic lymph node involvement on the three arms of the study in patients who have a lymph node dissection at the end of neoadjuvant treatment.
  7. Determine the 5-year incidence of local recurrence in patients treated with these regimens.
  8. Compare down-staging to Stage I, defined as a finding of 2 cm or less invasive cancer in the breast at surgery, with pathologically negatice lymph-nodes.
  9. Collect surgical specimens post-AI neoadjuvant therapy to identify markers of de novo resistence to AI therapy.

Entry Criteria

Disease Characteristics:

  • Diagnosis of breast cancer
    • T2-T4c, any N, M0 disease


  • Clinically staged, as documented by the operating surgeon, as 1 of the following:
    • T4a-c disease for which modified radical mastectomy with negative margins is the goal
    • T2 or T3 disease for which conversion from needing mastectomy to breast conservation is the goal
    • T2 disease for which lumpectomy at first attempt is the goal


  • Primary tumor must be palpable and measure > 2 cm by tape. ruler, or caliper measurements in at least one dimension


  • Must agree to undergo mastectomy or lumpectomy after neoadjuvant aromatase inhibitor therapy


  • No inflammatory breast cancer, defined as clinically significant erythema of the breast and/or documented dermal lymphatic invasion (not direct skin invasion by tumor or peau d’orange without erythema)


  • No distant metastasis (M1)
    • Isolated ipsilateral supraclavicular node involvement allowed


  • No diagnosis that was established by incisional biopsy


  • Must have estrogen receptor (ER) positive tumor with an Allred score of 6, 7 or 8
    • Patients with > 66.66% (two-thirds) of cells staining positive and have a minimum Allred score of 6 are eligible


Prior/Concurrent Therapy:

  • Any agent with estrogenic or putatively estrogenic properties, including herbal preparations, must be stopped at least one week prior to registration
  • No prior treatment for breast cancer, including radiation, endocrine therapy, chemotherapy, or investigational agent
  • No concurrent enrollment in another neoadjuvant clinical trial for treatment of the existing breast cancer
  • No hormone replacement therapy of any type, megestrol acetate, or raloxifene within one week prior to registration
  • No other concurrent anti-neoplastic approach such as chemotherapy or radiation therapy
  • Concomitant use of agents and herbal products that alter ER function are specifically not allowed

Patient Characteristics:

  • ECOG/Zubrod performance status of ≤ 2
  • Female
  • Patient must be postmenopausal, verified by 1 of the following:
    • Bilateral surgical oophorectomy
    • No spontaneous menses > 1 year
    • No menses for < 1 year with FSH and estradiol levels in postmenopausal range
  • If patient is a cancer survivor, all of the following criteria must be met:
    • Must have undergone potentially curative therapy for all prior malignancies
    • No evidence of any prior malignancies for at least 5 years with no evidence of recurrence (except for successfully treated cervical carcinoma in situ, lobular carcinoma in situ of the breast, or non-melanoma skin cancer with no evidence of recurrence)
    • Deemed by their treating physician to be at low risk for recurrence

Expected Enrollment

375

A total of 375 patients will be accrued for this study.

Outcomes

Primary Outcome(s)

Clinical response (complete or partial response) rate at baseline and week 16

Secondary Outcome(s)

Radiological response rate at baseline and week 16
Breast-conserving surgery rate
Overall survival
Surgical outcomes improvement rate
Local-regional failure rate
Comparison of tumor size
Adverse events rate ≥ grade 3
Lymph node involvement

Outline

This is a randomized, multicenter study. Patients are stratified according to T stage (T2 versus T3 versus T4). Patients are randomized to 1 of 3 treatment arms.

  • Arm I: Patients receive oral exemestane once daily for 16-18 weeks.


  • Arm II: Patients receive oral letrozole once daily for 16-18 weeks.


  • Arm III: Patients receive oral anastrozole once daily for 16-18 weeks.


All patients then undergo partial or radical mastectomy or lumpectomy with or without lymph node dissection.

After completion of study treatment, patients are followed periodically for 10 years.

Trial Contact Information

Trial Lead Organizations

American College of Surgeons Oncology Group

Matthew Ellis, MD, PhD, FRCP, Protocol chair
Ph: 314-362-8866
Email: mellis@im.wustl.edu
John Olson, MD, PhD, Protocol co-chair
Ph: 919-684-6523
Email: jaomd@duke.edu

Cancer and Leukemia Group B

Kevin Hughes, MD, FACS, Principal investigator
Ph: 617-724-4800
Email: kshughes@partners.org

Trial Sites

U.S.A.
Alaska
  Anchorage
 Providence Cancer Center
 Clinical Trials Office - Providence Cancer Center
Ph: 907-261-3109
California
  Oakland
 CCOP - Bay Area Tumor Institute
 James Feusner, MD
Ph: 510-428-3689
 Highland General Hospital
 James Feusner, MD
Ph: 510-428-3689
  Pleasanton
 Valley Care Medical Center
 James Feusner, MD
Ph: 510-428-3689
Georgia
  Valdosta
 Pearlman Comprehensive Cancer Center at South Georgia Medical Center
 Contact Person
Ph: 229-259-4600
Iowa
  Ames
 McFarland Clinic, PC
 Clinical Trials Office - McFarland Clinic, PC
Ph: 515-239-2621
Kentucky
  Edgewood
 Esther Marie Hatton Cancer Care Center at St. Elizabeth Medical Center
 Joseph Guenther, MD
Ph: 513-961-4335
Michigan
  Adrian
 Hickman Cancer Center at Bixby Medical Center
 Clinical Trials Office - Hickman Cancer Center at Bixby Medical Center
Ph: 517-265-0116
  Lambertville
 Haematology-Oncology Associates of Ohio and Michigan, PC
 Paul Schaefer, MD
Ph: 419-843-6147
  Monroe
 Community Cancer Center of Monroe
 Paul Schaefer, MD
Ph: 419-843-6147
 Mercy Memorial Hospital - Monroe
 Paul Schaefer, MD
Ph: 419-843-6147
Nevada
  Las Vegas
 CCOP - Nevada Cancer Research Foundation
 John Ellerton, MD, CM
Ph: 702-384-0013
 University Medical Center of Southern Nevada
 John Ellerton, MD, CM
Ph: 702-383-2000
New Jersey
  Marlton
 Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
 Clinical Trials Office - Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
Ph: 888-847-8823
  Voorhees
 Fox Chase Virtua Health Cancer Program at Virtua West Jersey
 Eric Miller, MD, FACS
Ph: 856-325-3671
North Carolina
  Winston-Salem
 Wake Forest University Comprehensive Cancer Center
 Clinical Trials Office - Wake Forest University Comprehensive Cancer Center
Ph: 336-713-6771
Ohio
  Bowling Green
 Wood County Oncology Center
 Paul Schaefer, MD
Ph: 419-843-6147
  Lima
 Lima Memorial Hospital
 Paul Schaefer, MD
Ph: 419-843-6147
  Maumee
 Northwest Ohio Oncology Center
 Paul Schaefer, MD
Ph: 419-843-6147
 Paul Schaefer, MD
Ph: 419-843-6147
 St. Luke's Hospital
 Paul Schaefer, MD
Ph: 419-843-6147
  Oregon
 St. Charles Mercy Hospital
 Paul Schaefer, MD
Ph: 419-843-6147
 Toledo Clinic - Oregon
 Paul Schaefer, MD
Ph: 419-843-6147
  Sandusky
 North Coast Cancer Care, Incorporated
 Paul Schaefer, MD
Ph: 419-843-6147
  Sylvania
 Flower Hospital Cancer Center
 Clinical Trials Office - Flower Hospital Cancer Center
Ph: 419-824-1842
  Tiffin
 Mercy Hospital of Tiffin
 Paul Schaefer, MD
Ph: 419-843-6147
  Toledo
 CCOP - Toledo Community Hospital
 Paul Schaefer, MD
Ph: 419-843-6147
 Medical University of Ohio Cancer Center
 Clinical Trials Office - Medical University of Ohio Cancer Center
Ph: 419-383-6583
 St. Vincent Mercy Medical Center
 Paul Schaefer, MD
Ph: 419-843-6147
 Toledo Clinic, Incorporated - Main Clinic
 Paul Schaefer, MD
Ph: 419-843-6147
 Toledo Hospital
 Clinical Trials Office - Toledo Hospital
Ph: 419-824-1842
  Wauseon
 Fulton County Health Center
 Clinical Trials Office - Fulton County Health Center
Ph: 419-330-2708
Pennsylvania
  York
 York Cancer Center at Apple Hill Medical Center
 Thomas Bauer, MD
Ph: 717-741-8100
877-441-7957
South Carolina
  West Columbia
 Lexington Medical Center
 Steven Madden
Ph: 803-791-2000
Texas
  Laredo
 Doctor's Hospital of Laredo
 Gary Unzeitig, MD
Ph: 956-726-3691
Virginia
  Fredericksburg
 Fredericksburg Oncology, Incorporated
 Paul Schaefer, MD
Ph: 419-843-6147

Related Information

Featured trial article

Registry Information
Official Title A Randomized Phase III Trial Comparing 16 to 18 Weeks of Neoadjuvant Exemestane (25 mg daily), Letrozole (2.5 mg), or Anastrozole (1 mg) in Postmenopausal Women with Clinical Stage II and III Estrogen Receptor Positive Breast Cancer
Trial Start Date 2006-01-09
Trial Completion Date 2008-08-03 (estimated)
Registered in ClinicalTrials.gov NCT00265759
Date Submitted to PDQ 2005-09-27
Information Last Verified 2008-08-21
NCI Grant/Contract Number CA76001

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.

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