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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
NSABP Foundation Inc
ClinicalTrials.gov Identifier:
NCT00016432
First received: May 6, 2001
Last updated: April 18, 2011
Last verified: April 2011
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: exemestane
Drug: Placebo
Phase 3

Study Type: Interventional
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
Official Title: 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

Resource links provided by NLM:


Further study details as provided by NSABP Foundation Inc:

Primary Outcome Measures:
  • Disease-free survival [ Time Frame: Every 12 months until breast cancer recurrence, second primary cancer or death from any cause. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: Death from any cause ] [ Designated as safety issue: No ]
  • Time to treatment failure [ Time Frame: time from randomization to recurrence or contralateral second primary cancer ] [ Designated as safety issue: No ]
  • Bone measure as measured by total alkaline phosphatase, fracture history, and height measurement [ Time Frame: measurements taken at regular intervals from randomization through 6 years following randomiztion ] [ Designated as safety issue: Yes ]

Enrollment: 1598
Study Start Date: May 2001
Study Completion Date: February 2011
Primary Completion Date: October 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
Exemestane
Drug: exemestane
25 mg for 5 years
Placebo Comparator: Group 2
Placebo
Drug: Placebo
Placebo

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00016432

  Show 162 Study Locations
Sponsors and Collaborators
NSABP Foundation Inc
Investigators
Principal Investigator: Norman Wolmark, MD NSABP Foundation Inc
  More Information

Additional Information:
Publications:
Responsible Party: Norman Wolmark, MD, NSABP Foundation, Inc.
ClinicalTrials.gov Identifier: NCT00016432     History of Changes
Other Study ID Numbers: NSABP B-33, CDR0000068640
Study First Received: May 6, 2001
Last Updated: April 18, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by NSABP Foundation Inc:
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Exemestane
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014