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

Alternate Title

Exemestane or Anastrozole in Treating Postmenopausal Women With Hormone Receptor-Positive Primary Breast Cancer (Closed to Accrual as of 7/31/2008)

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	45 and over	NCI	CAN-NCIC-MA27 (NON-COMPANION) NCIC-MA27 (NON-COMPANION), IBCSG-30-04, NCT00438529, MA27

Objectives

Primary

1. Compare the event-free survival of postmenopausal women with hormone receptor-positive breast cancer treated with adjuvant exemestane vs anastrozole.

Secondary

1. Compare the overall survival of patients treated with these regimens.
2. Compare the time to distant recurrence in patients treated with these regimens.
3. Compare the incidence of new contralateral primary breast cancer in patients treated with these regimens.
4. Compare the incidence of all clinical fractures, specifically hip and vertebral fractures, in patients treated with these regimens.
5. Compare cardiovascular morbidity and mortality in patients treated with these regimens.
6. Compare the toxicities of these regimens in these patients.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed invasive breast cancer meeting the following criteria:
  • Complete resection of primary tumor
    • Surgical margins must be clear of invasive carcinoma and ductal carcinoma in situ
  • Stage I-III (T1-3, N0-3, M0) disease
    • N3 allowed provided classification is solely based on presence of ≥ 10 involved axillary nodes



• Bilateral breast cancer allowed if cancers are synchronous (diagnosed at the same time)
  • One or both tumors must have hormone receptor-positive markers
  • No metachronous disease (diagnosed at different times)



• No locally recurrent or metastatic breast cancer
  • Negative for metastases by the following radiologic methods:
    • Bone scan
      • Required only if alkaline phosphatase is ≥ 2 times upper limit of normal (ULN) and/or symptoms of metastatic disease
      • Confirmatory x-ray or other imaging study (e.g., CT scan or MRI) required if bone scan results are questionable
    • Abdominal ultrasound or CT scan of the abdomen
      • Required only if AST/ALT or alkaline phosphatase ≥ 2 times ULN (except if the elevation is in the bone fraction)
    • Chest x-ray



• No prior diagnosis of in situ carcinoma in the contralateral breast treated with partial mastectomy and/or hormonal therapy
  • Prior or concurrent in situ carcinoma in the ipsilateral breast allowed if completely excised and patient did not receive hormonal therapy



• Hormone receptor status:
  • Estrogen or progesterone receptor-positive disease

Prior/Concurrent Therapy:

• See Disease Characteristics
• No prior aromatase inhibitor therapy
• No prior tamoxifen or selective estrogen-receptor modulators (SERMs) other than raloxifene
  • At least 3 weeks since prior raloxifene
• At least 3 weeks but < 3 months since prior chemotherapy
  • If no chemotherapy, > 3 weeks but < 3 months since prior primary surgery
• At least 3 weeks since prior and no concurrent hormones or steroids, including over-the-counter products and supplements considered to have an estrogenic effect including, but not limited to, any of the following:
  • Ginseng
  • EGb761 (ginkgo biloba)
  • Black cohosh
  • Angelica sinensis extract (dong quai)
  • Fortified soy supplements/phytoestrogen preparations
• Prior and/or concurrent radiotherapy allowed
• Prior and/or concurrent trastuzumab (Herceptin^®) allowed
• Concurrent bisphosphonates allowed for prevention or treatment for osteoporosis but not as adjuvant therapy for breast cancer
• No concurrent estrogens, progesterones, or androgens
  • Intermittent vaginal estrogens (e.g., estradiol, estrogen vaginal cream, or testosterone) for vaginal atrophy refractory to local measures allowed
• No concurrent SERMs
• No other concurrent endocrine therapy, hormonal therapy, steroids, or any other medication that would affect study endpoints

Patient Characteristics:

• Female
• Postmenopausal, defined as one of the following:
  • At least 60 years old
  • Age 45-59 years with spontaneous cessation of menses for > 12 months prior to chemotherapy or study randomization
  • Age 45-59 years with cessation of menses for < 12 months or secondary to hysterectomy AND a follicle-stimulating hormone (FSH) level in the postmenopausal range (or > 34.4 IU/L)
  • Age 45-59 years on hormone replacement therapy (HRT) and discontinued HRT at diagnosis of breast cancer AND FSH level in the postmenopausal range (or > 34.4 IU/L)
  • Bilateral oophorectomy
• ECOG performance status 0-2
• Life expectancy ≥ 5 years
• WBC ≥ 3,000/mm³ OR granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• AST and/or ALT < 2 times upper limit of normal*
• Alkaline phosphatase < 2 times ULN*
• No concurrent medical or psychiatric condition that would preclude study participation
• Able to swallow study medication and have adequate, unassisted oral intake to maintain a reasonable state of nutrition
• No history of other malignancies except adequately treated nonmelanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years

 [Note: *Unless imaging studies rule out metastases]

Expected Enrollment

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

Outcomes

Event-free survival

Overall survival
Time to distant recurrence
Incidence of new contralateral primary breast cancer
Long-term clinical and laboratory safety

Outline

This is a randomized, open-label, multicenter study. Patients are stratified according to lymph node status (negative vs positive vs unknown), prior adjuvant chemotherapy (yes vs no), and trastuzumab (Herceptin^®) use (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral exemestane once daily.



• Arm II: Patients receive oral anastrozole once daily.

In both arms, treatment continues for 5 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed annually.

Moy B, Elliott CR, Chapman JW, et al.: NCIC CTG MA.27: menopausal symptoms of ethnic minority women. [Abstract] American Society of Clinical Oncology 2007 Breast Cancer Symposium, 7-8 September 2007, San Francisco, California A-139, 2007.

Trial Contact Information

Trial Lead Organizations

NCIC-Clinical Trials Group

Paul Goss, MD, PhD, Protocol chair		Ph: 617-724-3118; 877-726-5130

North Central Cancer Treatment Group

James Ingle, MD, Protocol chair		Ph: 507-538-7623 Email: cancerclinicaltrials@mayo.edu

Eastern Cooperative Oncology Group

George Sledge, MD, Protocol chair		Ph: 317-274-1690; 888-600-4822 Email: gsledge@iupui.edu

Cancer and Leukemia Group B

Matthew Ellis, MD, PhD, FRCP, Protocol chair		Ph: 314-747-7502; 800-600-3606 Email: mellis@dom.wustl.edu

Southwest Oncology Group

George Budd, MD, Protocol chair		Ph: 216-444-6480; 800-862-7798

International Breast Cancer Study Group

Manuela Rabaglio, MD, Protocol chair		Ph: 41-31-632-4370 Email: manuela.rabaglio@insel.ch

Registry Information
Official Title		A Randomized Phase III Trial of Exemestane Versus Anastrozole in Postmenopausal Women with Receptor Positive Primary Breast Cancer
Trial Start Date		2006-12-19
Trial Completion Date		2011-01-01 (estimated)
Registered in ClinicalTrials.gov		NCT00438529
Date Submitted to PDQ		2007-01-08
Information Last Verified		2009-05-28
NCI Grant/Contract Number		CA77202

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