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Breast CancerPhase 3NCT00066573

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

A Phase 3 study testing anastrozole and exemestane in people with Breast Cancer, run by NCIC Clinical Trials Group at 39 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 120 years, women only
Conditions the study is for
Breast Cancer
What is being tested?
anastrozole and exemestane
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7,576 participants
Where
39 sitesCanada
Study dates
6 Jun 2003to 6 Jan 2012
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

39 sites in 1 country.

39 sites in 1 country

Canada39 sites

  • Quinte Healthcare Corporation

    Belleville, Ontario, K8N 5A9

  • Tom Baker Cancer Centre

    Calgary, Alberta, T2N 4N2

  • Cambridge Memorial Hospital

    Cambridge, Ontario, N1R 3G2

  • PEI Cancer Treatment Centre,Queen Elizabeth Hospital

    Charlottetown, Prince Edward Island, C1A 8T5

  • Centre de Sante et de services sociaux de Gatineau

    Gatineau, Quebec, J8P 7H2

  • Regional Cancer Program of the Hopital Regional

    Greater Sudbury, Ontario, P3E 5J1

  • Hopital Charles LeMoyne

    Greenfield Park, Quebec, J4V 2H1

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

  • BCCA - Cancer Centre for the Southern Interior

    Kelowna, British Columbia, V1Y 5L3

  • Cancer Centre of Southeastern Ontario at Kingston

    Kingston, Ontario, K7L 5P9

  • Grand River Regional Cancer Centre

    Kitchener, Ontario, N2G 1G3

  • Lethbridge Cancer Centre

    Lethbridge, Alberta, T1J 1W5

  • London Regional Cancer Program

    London, Ontario, N6A 4L6

  • Credit Valley Hospital

    Mississauga, Ontario, L5M 2N1

  • The Moncton Hospital

    Moncton, New Brunswick, E1C 6Z8

  • The Vitalite Health Network - Dr. Leon Richard

    Moncton, New Brunswick, E1C 8X3

  • CHUM - Hopital Notre-Dame

    Montreal, Quebec, H2L 4M1

  • Stronach Regional Health Centre at Southlake

    Newmarket, Ontario, L3Y 2P9

  • Lakeridge Health Oshawa

    Oshawa, Ontario, L1G 2B9

  • Penticton Regional Hospital

    Penticton, British Columbia, V2A 3G6

  • CHA-Hopital Du St-Sacrement

    Québec, Quebec, G1S 4L8

  • Allan Blair Cancer Centre

    Regina, Saskatchewan, S4T 7T1

  • Atlantic Health Sciences Corporation

    Saint John, New Brunswick, E2L 4L2

  • Saskatoon Cancer Centre

    Saskatoon, Saskatchewan, S7N 4H4

  • Algoma District Cancer Program

    Sault Ste. Marie, Ontario, P6B 0A8

  • Centre hospitalier universitaire de Sherbrooke

    Sherbrooke, Quebec, J1H 5N4

  • Niagara Health System

    St. Catharines, Ontario, L2R 7C6

  • Dr. H. Bliss Murphy Cancer Centre

    St. John's, Newfoundland and Labrador, AIB 3V6

  • BCCA - Fraser Valley Cancer Centre

    Surrey, British Columbia, V3V 1Z2

  • Thunder Bay Regional Health Science Centre

    Thunder Bay, Ontario, P7B 6V4

  • Odette Cancer Centre

    Toronto, Ontario, M4N 3M5

  • St. Michael's Hospital

    Toronto, Ontario, M5B 1W8

  • Mount Sinai Hospital

    Toronto, Ontario, M5G 1X5

  • Univ. Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

  • Trillium Health Centre - West Toronto

    Toronto, Ontario, M9C 1A5

  • BCCA - Vancouver Cancer Centre

    Vancouver, British Columbia, V5Z 4E6

  • BCCA - Vancouver Island Cancer Centre

    Victoria, British Columbia, V8R 6V5

  • Windsor Regional Cancer Centre

    Windsor, Ontario, N8W 2X3

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

About this study

Official title: 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.

Read the 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.

Conditions
Breast Cancer
Being tested
anastrozole, exemestane
Keywords
stage IIIA breast cancer, stage I breast cancer, stage II breast cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00066573
Study groupRoleWhat they receive
ExemestaneExperimentalPatients receive oral exemestane (25 mg) once daily for 5 years.
Receives: Drug: exemestane
AnastrozoleActive comparatorPatients receive oral anastrozole (1 mg) once daily for 5 years.
Receives: Drug: anastrozole

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event-free Survival

    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.

    Measured: 5 years

Secondary outcomes (3)

  1. Overall Survival: Percentage of Participants Alive at 5 Years

    Overall survival is defined as the time from randomization to the time of death from any cause.

    Measured: 5 years

  2. Distant Disease-free Survival: Number of Participants Without Documented Distant Recurrence

    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.

    Measured: 5 years

  3. Clinical Fracture Rate: Number of Participants With Bone Fractures.

    Clinical fracture at any time, including hip, spine, wrist fractures and other bone fractures.

    Measured: 8 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Aug 2003 (estimated)
  2. Study start6 Jun 2003
  3. Primary completion7 Nov 2010
  4. Study completion6 Jan 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
7,576 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00066573
Sponsor's protocol ID
MA27
Other IDs
CAN-NCIC-MA27, NCCTG-MA27, CALGB-CAN-NCIC-MA27, ECOG-CAN-NCIC-MA27, SWOG-CAN-NCIC-MA27, IBCSG-30-04, 2005-001893-28, CDR0000316325
Status last verified
Mar 2020
First submitted
6 Aug 2003
Last updated
25 Aug 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Moy B, Elliott CR, Chapman J-AW, et al.: NCIC CTG MA.27: menopausal symptoms of ethnic minority women. [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-3059, S144, 2006.

  • Goss PE, Ingle JN, Pritchard KI, Ellis MJ, Sledge GW, Budd GT, Rabaglio M, Ansari RH, Johnson DB, Tozer R, D'Souza DP, Chalchal H, Spadafora S, Stearns V, Perez EA, Liedke PE, Lang I, Elliott C, Gelmon KA, Chapman JA, Shepherd LE. Exemestane versus anastrozole in postmenopausal women with early breast cancer: NCIC CTG MA.27--a randomized controlled phase III trial. J Clin Oncol. 2013 Apr 10;31(11):1398-404. doi: 10.1200/JCO.2012.44.7805. Epub 2013 Jan 28.

    PubMed 23358971

  • Pilgram L, Yang K, Beltran-Bless AA, Pond GR, Vandermeer L, Hilton J, Savard MF, LeBlanc A, Shepherd L, Chen B, Bartlett JM, Taylor KJ, Bayani J, Barker S, Spears M, van der Velde CJ, Meershoek-Klein Kranenbarg E, Dirix L, Mallon E, Hasenburg A, Markopoulos C, Juwara L, Dankar FK, Clemons M, El Emam K. Transfer Learning and Machine Learning for Training Five-Year Survival Prognostic Models in Early Breast Cancer: Development and Validation Study. J Med Internet Res. 2026 Apr 14;28:e88665. doi: 10.2196/88665.

    PubMed 41980703

  • Chapman JW, Bayani J, SenGupta S, Bartlett JMS, Piper T, Quintayo MA, Virk S, Goss PE, Ingle JN, Ellis MJ, Sledge GW, Budd GT, Rabaglio M, Ansari RH, Tozer R, D'Souza DP, Chalchal H, Spadafora S, Stearns V, Perez EA, Gelmon KA, Whelan TJ, Elliott C, Shepherd LE, Chen BE, Taylor KJ. Adjunctive Statistical Standardization of Adjuvant Estrogen Receptor and Progesterone Receptor in Canadian Cancer Trials Group MA.27 Postmenopausal Breast Cancer Trial of Exemestane Versus Anastrozole. J Clin Oncol. 2024 Aug 20;42(24):2887-2898. doi: 10.1200/JCO.24.00835. Epub 2024 Jun 2.

    PubMed 38824432

  • Ethier JL, Anderson GM, Austin PC, Clemons M, Parulekar W, Shepherd L, Summers Trasiewicz L, Tu D, Amir E. Influence of the competing risk of death on estimates of disease recurrence in trials of adjuvant endocrine therapy for early-stage breast cancer: A secondary analysis of MA.27, MA.17 and MA.17R. Eur J Cancer. 2021 May;149:117-127. doi: 10.1016/j.ejca.2021.02.034. Epub 2021 Apr 11.

    PubMed 33853037

  • Strasser-Weippl K, Higgins MJ, Chapman JW, Ingle JN, Sledge GW, Budd GT, Ellis MJ, Pritchard KI, Clemons MJ, Badovinac-Crnjevic T, Han L, Gelmon KA, Rabaglio M, Elliott C, Shepherd LE, Goss PE. Effects of Celecoxib and Low-dose Aspirin on Outcomes in Adjuvant Aromatase Inhibitor-Treated Patients: CCTG MA.27. J Natl Cancer Inst. 2018 Sep 1;110(9):1003-1008. doi: 10.1093/jnci/djy017.

    PubMed 29554282

  • Strasser-Weippl K, Sudan G, Ramjeesingh R, Shepherd LE, O'Shaughnessy J, Parulekar WR, Liedke PER, Chen BE, Goss PE. Outcomes in women with invasive ductal or invasive lobular early stage breast cancer treated with anastrozole or exemestane in CCTG (NCIC CTG) MA.27. Eur J Cancer. 2018 Feb;90:19-25. doi: 10.1016/j.ejca.2017.11.014. Epub 2017 Dec 20.

    PubMed 29274617

  • Yerushalmi R, Dong B, Chapman JW, Goss PE, Pollak MN, Burnell MJ, Levine MN, Bramwell VHC, Pritchard KI, Whelan TJ, Ingle JN, Shepherd LE, Parulekar WR, Han L, Ding K, Gelmon KA. Impact of baseline BMI and weight change in CCTG adjuvant breast cancer trials. Ann Oncol. 2017 Jul 1;28(7):1560-1568. doi: 10.1093/annonc/mdx152.

    PubMed 28379421

  • Stearns V, Chapman JA, Ma CX, Ellis MJ, Ingle JN, Pritchard KI, Budd GT, Rabaglio M, Sledge GW, Le Maitre A, Kundapur J, Liedke PE, Shepherd LE, Goss PE. Treatment-associated musculoskeletal and vasomotor symptoms and relapse-free survival in the NCIC CTG MA.27 adjuvant breast cancer aromatase inhibitor trial. J Clin Oncol. 2015 Jan 20;33(3):265-71. doi: 10.1200/JCO.2014.57.6926. Epub 2014 Dec 15.

    PubMed 25512454

  • Goetz MP, Schaid DJ, Wickerham DL, Safgren S, Mushiroda T, Kubo M, Batzler A, Costantino JP, Vogel VG, Paik S, Carlson EE, Flockhart DA, Wolmark N, Nakamura Y, Weinshilboum RM, Ingle JN, Ames MM. Evaluation of CYP2D6 and efficacy of tamoxifen and raloxifene in women treated for breast cancer chemoprevention: results from the NSABP P1 and P2 clinical trials. Clin Cancer Res. 2011 Nov 1;17(21):6944-51. doi: 10.1158/1078-0432.CCR-11-0860. Epub 2011 Aug 31.

    PubMed 21880792

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing anastrozole and exemestane in people with Breast Cancer, run by NCIC Clinical Trials Group at 39 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 39 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-free Survival (time frame: 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00066573, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2023.

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