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A Randomized Trial Evaluating The Effect Of Exemestane In Clinical Stage T1-3 N0-1 M0 Postmenopausal Breast Cancer Patients Completing At Least Five Years Of Tamoxifen Therapy

Phase 3
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

A Randomized Trial Evaluating The Effect Of Exemestane In Clinical Stage T1-3 N0-1 M0 Postmenopausal Breast Cancer Patients Completing At Least Five Years Of Tamoxifen Therapy


- Determine whether the administration of 5 years of exemestane after 5 years of
tamoxifen therapy is more effective than 5 years of prior tamoxifen therapy alone in
prolonging disease-free survival, overall survival, and time to treatment failure in
postmenopausal women with resected stage I, II, or IIIA breast cancer.

- Determine the effect of tamoxifen withdrawal on bone, in terms of height, fractures,
and total alkaline phosphatase in these patients and on bone mineral density and bone
biochemical markers in a subset of patients.

- Determine the effect of exemestane on bone loss after tamoxifen withdrawal in these

- Evaluate the quality of life of a subset of these patients.

OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive oral exemestane daily for 5 years.

- Arm II (closed as of 10/15/03): Patients receive an oral placebo daily for 5 years.

Quality of life is assessed at baseline and then every 6 months for 5.5 years.

Patients are followed every 6 months for 6 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 3,000 patients will be accrued for this study within 3 years
and 4 months.

Inclusion Criteria


- Histologically confirmed invasive adenocarcinoma of the breast at time of original

- Tumor confined to the breast and ipsilateral axilla on clinical exam (T1-3,
N0-1, M0) (stage I-IIIA)

- No ipsilateral lymph nodes clinically fixed to one another or to other
structures (N2 disease) at time of original diagnosis

- Prior surgical resection, including 1 of the following:

- Total mastectomy and axillary dissection (modified radical mastectomy) OR

- Lumpectomy and axillary dissection

- Prior post-lumpectomy breast radiotherapy required

- Prior sentinel node biopsy allowed with the exception of the following:

- If any sentinel node is histologically positive by hematoxylin and eosin (H
& E) OR histologically suspicious on H & E and confirmed positive by
immunohistochemistry then the patient must have a complete axillary

- Previously resected margins must be clear of invasive tumor and ductal carcinoma
in situ

- Currently disease free

- Previously treated with tamoxifen for 57-66 months

- Completed tamoxifen within the past 180 days

- No bilateral malignancy or mass in the opposite breast suspicious for malignancy
unless biopsy proven negative

- No local, regional, or distant recurrence of disease or second primary breast
malignancy (including contralateral breast cancer)

- No advanced disease at time of original diagnosis (e.g., ulceration, erythema,
infiltration of the skin or underlying chest wall [complete fixation], peau d'orange,
or skin edema of any magnitude)

- Tethering or dimpling of the skin or nipple inversion allowed

- Current skeletal pain allowed if a bone scan and/or radiologic exam is negative for
metastatic disease

- Hormone receptor status:

- Primary tumor estrogen receptor (ER) positive AND/OR

- Progesterone receptor positive

- Borderline ER positive tumors allowed if previously treated with tamoxifen



- Postmenopausal


- Female

Menopausal status:

- Postmenopausal, defined as 1 of the following:

- Prior bilateral oophorectomy

- Absence of spontaneous menstrual cycle for more than 1 year

- Follicle-stimulating hormone within the postmenopausal range if under 55 and had
a prior hysterectomy without a bilateral oophorectomy

Performance status:

- Not specified

Life expectancy:

- At least 10 years


- Absolute granulocyte count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- Hemoglobin normal


- Bilirubin less than 2 times upper limit of normal (ULN)

- SGOT or SGPT no greater than 2.5 times ULN

- Alkaline phosphatase less than 2 times ULN

- No systemic hepatic disease that would preclude study participation


- Creatinine no greater than 1.5 times ULN

- No systemic renal disease that would preclude study participation


- No systemic cardiovascular disease that would preclude study participation


- No other malignancy within the past 5 years except effectively treated squamous cell
or basal cell skin cancer, surgically treated carcinoma in situ of the cervix, or
surgically treated lobular carcinoma in situ of the ipsilateral or contralateral

- No nonmalignant systemic disease that would preclude study participation

- No psychiatric or addictive disorder that would preclude informed consent

- Not pregnant


Biologic therapy:

- Not specified


- Prior adjuvant chemotherapy allowed if administered concurrently with or prior to

Endocrine therapy:

- See Disease Characteristics

- No concurrent estrogen, progesterone, clomiphene, testosterone,
gonadotropin-releasing hormone, oral contraceptives, selective estrogen-receptor
modulators, or dehydroepiandrosterone (DHEA)

- Estring or estrogen vaginal cream at 0.3 mg or 1/8 of an applicator applied
vaginally 3 times a week allowed

- No other concurrent systemic hormonal therapy (e.g., tamoxifen or raloxifene)


- See Disease Characteristics

- Prior post-mastectomy loco-regional radiotherapy or post-lumpectomy regional
radiotherapy allowed


- See Disease Characteristics


- Prior participation in other adjuvant NSABP study allowed if study was reported in
peer-review publication or tamoxifen was not a study drug

- Concurrent bisphosphonates or calcitonin for prevention or treatment of osteoporosis

- Concurrent statins (simvastatin, pravastatin, fluvastatin, atorvastatin, or
lovastatin) or other drugs to control lipid levels allowed

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

Disease-free survival

Outcome Time Frame:

Every 12 months until breast cancer recurrence, second primary cancer or death from any cause.

Safety Issue:


Principal Investigator

Norman Wolmark, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

NSABP Foundation, Inc.


United States: Food and Drug Administration

Study ID:




Start Date:

May 2001

Completion Date:

February 2011

Related Keywords:

  • Breast Cancer
  • stage I breast cancer
  • stage II breast cancer
  • stage IIIA breast cancer
  • Breast Neoplasms



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