Exemestane or Anastrozole in Treating Postmenopausal Women Who Have Undergone Surgery for Primary Breast Cancer

August 3, 2023 updated by: NCIC Clinical Trials Group

A Randomized Phase III Trial Of Exemestane Versus Anastrozole In Postmenopausal Women With Receptor Positive Primary Breast Cancer

RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy, using exemestane or anastrozole, may fight breast cancer by reducing the production of estrogen. It is not yet known whether exemestane is more effective than anastrozole in preventing the recurrence of breast cancer.

PURPOSE: This randomized phase III trial is studying exemestane to see how well it works compared to anastrozole in preventing cancer recurrence in postmenopausal women who have undergone surgery for primary breast cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Compare the event-free survival of postmenopausal women with receptor-positive primary breast cancer when treated with exemestane vs anastrozole.

Secondary

  • Compare the overall survival of patients treated with these regimens.
  • Compare the time to distant recurrence in patients treated with these regimens.
  • Compare the incidence of new primary contralateral breast cancer in patients treated with these regimens.
  • Compare the incidence of all clinical fractures, specifically hip and vertebral fractures, in patients treated with these regimens.
  • Compare cardiovascular morbidity and mortality (i.e., significant coronary heart disease, which includes myocardial infarctions and angina requiring percutaneous transluminal coronary angioplasty or coronary artery bypass graft, fatal and nonfatal strokes, and all vascular deaths) in patients treated with these regimens.
  • Correlate therapy induced changes in breast density with plasma hormones and growth factors, drug levels of exemestane and anastrozole, genetic variation and breast cancer recurrence or contralateral events in patients treated with these regimens.
  • Compare the toxic effects of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to lymph node status at diagnosis (negative vs positive vs unknown), prior adjuvant chemotherapy (yes vs no), and herceptin use (yes vs no). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral exemestane (25 mg) once daily for 5 years.
  • Arm II: Patients receive oral anastrozole (1 mg) once daily for 5 years. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 6 months during the first year of study participation and annually thereafter.

PROJECTED ACCRUAL: A total of 6,840 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Actual)

7576

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Tom Baker Cancer Centre
      • Lethbridge, Alberta, Canada, T1J 1W5
        • Lethbridge Cancer Centre
    • British Columbia
      • Kelowna, British Columbia, Canada, V1Y 5L3
        • BCCA - Cancer Centre for the Southern Interior
      • Penticton, British Columbia, Canada, V2A 3G6
        • Penticton Regional Hospital
      • Surrey, British Columbia, Canada, V3V 1Z2
        • BCCA - Fraser Valley Cancer Centre
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • BCCA - Vancouver Cancer Centre
      • Victoria, British Columbia, Canada, V8R 6V5
        • BCCA - Vancouver Island Cancer Centre
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 0V9
        • CancerCare Manitoba
    • New Brunswick
      • Moncton, New Brunswick, Canada, E1C 6Z8
        • The Moncton Hospital
      • Moncton, New Brunswick, Canada, E1C 8X3
        • The Vitalite Health Network - Dr. Leon Richard
      • Saint John, New Brunswick, Canada, E2L 4L2
        • Atlantic Health Sciences Corporation
    • Newfoundland and Labrador
      • St. John's, Newfoundland and Labrador, Canada, AIB 3V6
        • Dr. H. Bliss Murphy Cancer Centre
    • Ontario
      • Belleville, Ontario, Canada, K8N 5A9
        • Quinte Healthcare Corporation
      • Cambridge, Ontario, Canada, N1R 3G2
        • Cambridge Memorial Hospital
      • Hamilton, Ontario, Canada, L8V 5C2
        • Juravinski Cancer Centre at Hamilton Health Sciences
      • Kingston, Ontario, Canada, K7L 5P9
        • Cancer Centre of Southeastern Ontario at Kingston
      • Kitchener, Ontario, Canada, N2G 1G3
        • Grand River Regional Cancer Centre
      • London, Ontario, Canada, N6A 4L6
        • London Regional Cancer Program
      • Mississauga, Ontario, Canada, L5M 2N1
        • Credit Valley Hospital
      • Newmarket, Ontario, Canada, L3Y 2P9
        • Stronach Regional Health Centre at Southlake
      • Oshawa, Ontario, Canada, L1G 2B9
        • Lakeridge Health Oshawa
      • Sault Ste. Marie, Ontario, Canada, P6B 0A8
        • Algoma District Cancer Program
      • St. Catharines, Ontario, Canada, L2R 7C6
        • Niagara Health System
      • Sudbury, Ontario, Canada, P3E 5J1
        • Regional Cancer Program of the Hopital Regional
      • Thunder Bay, Ontario, Canada, P7B 6V4
        • Thunder Bay Regional Health Science Centre
      • Toronto, Ontario, Canada, M5B 1W8
        • St. Michael's Hospital
      • Toronto, Ontario, Canada, M5G 1X5
        • Mount Sinai Hospital
      • Toronto, Ontario, Canada, M4N 3M5
        • Odette Cancer Centre
      • Toronto, Ontario, Canada, M5G 2M9
        • Univ. Health Network-Princess Margaret Hospital
      • Toronto, Ontario, Canada, M9C 1A5
        • Trillium Health Centre - West Toronto
      • Windsor, Ontario, Canada, N8W 2X3
        • Windsor Regional Cancer Centre
    • Prince Edward Island
      • Charlottetown, Prince Edward Island, Canada, C1A 8T5
        • PEI Cancer Treatment Centre,Queen Elizabeth Hospital
    • Quebec
      • Gatineau, Quebec, Canada, J8P 7H2
        • Centre de Sante et de services sociaux de Gatineau
      • Greenfield Park, Quebec, Canada, J4V 2H1
        • Hopital Charles LeMoyne
      • Montreal, Quebec, Canada, H2L 4M1
        • CHUM - Hopital Notre-Dame
      • Quebec City, Quebec, Canada, G1S 4L8
        • CHA-Hopital Du St-Sacrement
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • Centre Hospitalier Universitaire de Sherbrooke
    • Saskatchewan
      • Regina, Saskatchewan, Canada, S4T 7T1
        • Allan Blair Cancer Centre
      • Saskatoon, Saskatchewan, Canada, S7N 4H4
        • Saskatoon Cancer Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed invasive breast cancer

    • pT1-3; pNX, pN0-2 or pN3*; M0
    • Neoadjuvant patients are eligible no earlier than 3 weeks or later than 3 months after excisional surgery, provided both the clinical-diagnostic staging of cancer and postsurgical resection-pathologic staging of cancer meet the requirements for primary tumor, regional lymph nodes, and distant metastasis classification NOTE: *Only when the sole basis for this classification is the presence of 10 or more involved axillary lymph nodes

  • Completely resected disease

    • Primary surgery performed at least 3 weeks but no more than 3 months before study entry (if no chemotherapy was given)

      • Primary surgery is defined as the last surgery at which histologic evidence of invasive or in situ disease was present in the pathology specimen
    • Patients with positive sentinel lymph node biopsy are eligible provided they have had a subsequent axillary lymph node dissection
  • No metachronous breast cancer
  • Bilateral mammogram within the past 12 months unless initial surgery was a total mastectomy, in which case only a mammogram of the remaining breast is required

  • No metastases confirmed by 1 of the following methods:

    • Bone scan* (required only if alkaline phosphatase is at least 2 times normal and/or there are symptoms of metastatic disease)
    • Abdominal ultrasound or CT scan (required only if AST/ALT or alkaline phosphatase is at least 2 times normal, unless the elevation is in the bone fraction)
    • Chest x-ray NOTE: *Confirmatory x-ray, CT scan, or MRI required if the bone scan results are questionable
  • No locally recurrent disease

  • No prior or concurrent carcinoma in situ of the contralateral breast treated with partial mastectomy and/or hormonal therapy

    • Patients with prior or concurrent carcinoma in situ of the ipsilateral breast are eligible provided the tumor was completely excised AND they have not received prior hormonal therapy

  • Hormone receptor status:

    • Estrogen receptor- and/or progesterone receptor-positive by immunohistochemistry or tumor receptor content ≥ 10 fmol/mg protein

PATIENT CHARACTERISTICS:

Age

  • Postmenopausal

Sex

  • Female

Menopausal status

  • Postmenopausal prior to chemotherapy, defined as 1 of the following:

    • Over 60 years of age
    • Age 45-59 with spontaneous cessation of menses for more than 1 year prior to study entry
    • Age 45-59 with menses ceasing (secondary to hysterectomy or spontaneously) within the past year AND a follicle-stimulating hormone (FSH) level prior to study entry in the postmenopausal range*
    • Age 45-59, previously on hormone replacement therapy (HRT) and have discontinued HRT upon diagnosis of this malignancy AND has an FSH level prior to study entry in the postmenopausal range*
    • Has undergone bilateral oophorectomy NOTE: *By institutional standards OR > 34.4 IU/L if institutional range is not available)

Performance status

  • ECOG 0-2

Life expectancy

  • At least 5 years

Hematopoietic

  • WBC at least 3,000/mm^3 OR
  • Granulocyte count at least 1,500/mm^3 AND
  • Platelet count at least 100,000/mm^3

Hepatic

  • See Disease Characteristics
  • AST and/or ALT less than 2 times upper limit of normal (ULN)*
  • Alkaline phosphatase less than 2 times ULN* NOTE: *Unless imaging examinations have ruled out metastatic disease

Renal

  • Not specified

Other

  • Able to swallow study medication and have adequate unassisted oral intake in order to maintain reasonable nutrition status
  • No other non-breast malignancy within the past 5 years except adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other curatively treated solid tumors with no evidence of disease for at least 5 years
  • No other concurrent medical or psychiatric condition that would preclude study participation and/or interfere with results

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Prior and concurrent trastuzumab (Herceptin®) allowed

Chemotherapy

  • See Disease Characteristics
  • At least 3 weeks but no more than 3 months since prior chemotherapy
  • Prior adjuvant chemotherapy allowed

Endocrine therapy

  • See Disease Characteristics
  • No prior aromatase inhibitor

  • No prior tamoxifen or other selective estrogen receptor modulators (SERMs) except raloxifene

    • At least 3 weeks since prior raloxifene

  • At least 3 weeks since prior and no concurrent over-the-counter products or supplements considered to have an estrogenic effect, including any of the following:

    • Ginseng
    • Ginkgo biloba
    • Black cohosh
    • Dong quai
    • Fortified soy supplements (e.g., phytoestrogen preparations)
  • At least 3 weeks since other prior hormonal therapy or steroids considered to have an estrogenic effect

  • No concurrent estrogens, progesterones, androgens, or SERMs

    • Concurrent intermittent vaginal estrogens (e.g., vagifem, estrogen vaginal cream, testosterone, estradiol vaginal gel, or Estring) allowed if other local measures for intractable vaginal atrophy are insufficient
  • No other concurrent therapy that would have an estrogenic effect, including endocrine therapy, hormonal therapy, or steroid therapy

Radiotherapy

  • See Disease Characteristics
  • Prior adjuvant radiotherapy allowed
  • Concurrent radiotherapy allowed

Surgery

  • See Disease Characteristics

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Exemestane
Patients receive oral exemestane (25 mg) once daily for 5 years.
Drug: exemestane
Given orally
Active Comparator: Anastrozole
Patients receive oral anastrozole (1 mg) once daily for 5 years.
Drug: anastrozole
Given orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free Survival
Time Frame: 5 years
Event free survival, the primary endpoint of this study, is defined as the time from randomization to the time of documented locoregional or distant recurrence, new primary breast cancer, or death from any cause.
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival: Percentage of Participants Alive at 5 Years
Time Frame: 5 years
Overall survival is defined as the time from randomization to the time of death from any cause.
5 years
Distant Disease-free Survival: Number of Participants Without Documented Distant Recurrence
Time Frame: 5 years
Time to distant disease-free survival (DDFS) is defined as the time from randomization to the time of documented distant recurrence. Distant recurrence is the cancer coming back in a part of the body away from the breast, such as the bones or liver.
5 years
Clinical Fracture Rate: Number of Participants With Bone Fractures.
Time Frame: 8 years
Clinical fracture at any time, including hip, spine, wrist fractures and other bone fractures.
8 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NCIC Clinical Trials Group

Collaborators

National Cancer Institute (NCI)
Eastern Cooperative Oncology Group
Cancer and Leukemia Group B
ETOP IBCSG Partners Foundation
North Central Cancer Treatment Group
SWOG Cancer Research Network

Investigators

  • Study Chair: James N. Ingle, MD, Mayo Clinic
  • Study Chair: Paul E. Goss, MD, PhD, Massachusetts General Hospital
  • Study Chair: Matthew J. Ellis, MD, PhD, FRCP, Washington University Siteman Cancer Center
  • Study Chair: George W. Sledge, MD, Indiana University Melvin and Bren Simon Cancer Center
  • Study Chair: George T. Budd, MD, The Cleveland Clinic
  • Principal Investigator: Manuela Rabaglio, MD, Insel Gruppe AG, University Hospital Bern

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 6, 2003

Primary Completion (Actual)

November 7, 2010

Study Completion (Actual)

January 6, 2012

Study Registration Dates

First Submitted

August 6, 2003

First Submitted That Met QC Criteria

August 6, 2003

First Posted (Estimated)

August 7, 2003

Study Record Updates

Last Update Posted (Actual)

August 25, 2023

Last Update Submitted That Met QC Criteria

August 3, 2023

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MA27
  • CAN-NCIC-MA27 (Other Identifier: Cancer.gov)
  • NCCTG-MA27 (Other Identifier: NCCTG)
  • CALGB-CAN-NCIC-MA27 (Other Identifier: CALGB)
  • ECOG-CAN-NCIC-MA27 (Other Identifier: ECOG)
  • SWOG-CAN-NCIC-MA27 (Other Identifier: SWOG)
  • IBCSG-30-04 (Other Identifier: IBCSG)
  • 2005-001893-28 (EudraCT Number)
  • CDR0000316325 (Other Identifier: PDQ)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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