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

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

Outcomes

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

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

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

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