Exemestane in Treating Postmenopausal Women With Resected Stage I, Stage II, or Stage IIIA Breast Cancer Who Have Completed 5 Years of Tamoxifen

National Surgical Adjuvant Breast and Bowel Project Foundation (NSABP)

Status and phase: Completed; Phase 3

Conditions: Breast Cancer

Treatments: Drug: exemestane; Drug: Placebo

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00016432

NSABP B-33

CDR0000068640

Details and patient eligibility

About

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

PURPOSE: Randomized phase III trial to study the effectiveness of exemestane in preventing cancer recurrence in postmenopausal women who have resected stage I, stage II, or stage IIIA breast cancer and have completed 5 years of tamoxifen.

Full description

OBJECTIVES:

• 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 patients.
• 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.

Enrollment: 1,598 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive adenocarcinoma of the breast at time of original diagnosis

  • 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 dissection

  • 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

PATIENT CHARACTERISTICS:

Age:

• Postmenopausal

Sex:

• 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

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin normal

Hepatic:

• 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

Renal:

• Creatinine no greater than 1.5 times ULN
• No systemic renal disease that would preclude study participation

Cardiovascular:

• No systemic cardiovascular disease that would preclude study participation

Other:

• 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 breast
• No nonmalignant systemic disease that would preclude study participation
• No psychiatric or addictive disorder that would preclude informed consent
• Not pregnant

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Prior adjuvant chemotherapy allowed if administered concurrently with or prior to tamoxifen

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)

Radiotherapy:

• See Disease Characteristics
• Prior post-mastectomy loco-regional radiotherapy or post-lumpectomy regional radiotherapy allowed

Surgery:

• See Disease Characteristics

Other:

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Quadruple Blind

---

1,598 participants in 2 patient groups, including a placebo group

Group 1

Experimental group

Description:

Exemestane

Treatment:

Drug: exemestane

Group 2

Placebo Comparator group

Description:

Placebo

Treatment:

Drug: Placebo