Know Cancer

forgot password

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



Akron City Hospital Akron, Ohio  44304
Baylor College of Medicine Houston, Texas  77030
National Naval Medical Center Bethesda, Maryland  20889
George Washington University Medical Center Washington, District of Columbia  20037
Jonsson Comprehensive Cancer Center, UCLA Los Angeles, California  90095-1781
Chao Family Comprehensive Cancer Center Orange, California  92868
Stanford University Medical Center Stanford, California  94305-5408
University of Colorado Cancer Center Denver, Colorado  80262
Rush-Presbyterian-St. Luke's Medical Center Chicago, Illinois  60612
Lineberger Comprehensive Cancer Center, UNC Chapel Hill, North Carolina  27599-7295
Ireland Cancer Center Cleveland, Ohio  44106-5065
Arthur G. James Cancer Hospital - Ohio State University Columbus, Ohio  43210
Kimmel Cancer Center of Thomas Jefferson University - Philadelphia Philadelphia, Pennsylvania  19107
CCOP - Upstate Carolina Spartanburg, South Carolina  29303
Simmons Cancer Center - Dallas Dallas, Texas  75235-9154
St. Luke's Medical Center Milwaukee, Wisconsin  53215
Sylvester Cancer Center, University of Miami Miami, Florida  33136
CCOP - Wichita Wichita, Kansas  67214-3882
East Carolina University School of Medicine Greenville, North Carolina  27858-4354
University of Texas Health Science Center at San Antonio San Antonio, Texas  78284-7811
Vermont Cancer Center Burlington, Vermont  05401-3498
CCOP - Greater Phoenix Phoenix, Arizona  85006-2726
CCOP - Kansas City Kansas City, Missouri  64131
CCOP - Missouri Valley Cancer Consortium Omaha, Nebraska  68131
CCOP - Southern Nevada Cancer Research Foundation Las Vegas, Nevada  89106
CCOP - Christiana Care Health Services Wilmington, Delaware  19899
CCOP - Mount Sinai Medical Center Miami Beach, Florida  33140
Ellis Fischel Cancer Center - Columbia Columbia, Missouri  65203
CCOP - Southeast Cancer Control Consortium Winston-Salem, North Carolina  27104-4241
CCOP - Illinois Oncology Research Association Peoria, Illinois  61602
CCOP - Carle Cancer Center Urbana, Illinois  61801
CCOP - Iowa Oncology Research Association Des Moines, Iowa  50309-1016
CCOP - Kalamazoo Kalamazoo, Michigan  49007-3731
CCOP - Metro-Minnesota Saint Louis Park, Minnesota  55416
CCOP - Northern New Jersey Hackensack, New Jersey  07601
University of Pittsburgh Cancer Institute Pittsburgh, Pennsylvania  15213
St. Vincent Hospital and Health Care Center Indianapolis, Indiana  46260
CCOP - Michigan Cancer Research Consortium Ann Arbor, Michigan  48106
CCOP - Duluth Duluth, Minnesota  55805
Geisinger Medical Center Danville, Pennsylvania  17822-0001
Medical College of Wisconsin Cancer Center Milwaukee, Wisconsin  53226
MD Anderson Cancer Center Orlando Orlando, Florida  32806
CCOP - Ochsner New Orleans, Louisiana  70121
CCOP - Merit Care Hospital Fargo, North Dakota  58122
CCOP - Sioux Community Cancer Consortium Sioux Falls, South Dakota  57105-1080
Comprehensive Cancer Center at Wake Forest University Winston-Salem, North Carolina  27157-1082
Huntsman Cancer Institute Salt Lake City, Utah  84112
California Cancer Center Fresno, California  93720
Sutter Health Western Division Cancer Research Group Greenbrae, California  94904
CCOP - Santa Rosa Memorial Hospital Santa Rosa, California  95403
Halifax Medical Center Daytona Beach, Florida  32114
CCOP - Central Illinois Springfield, Illinois  62526
St. Louis University Health Sciences Center Saint Louis, Missouri  63110-0250
CCOP - Cancer Research for the Ozarks Springfield, Missouri  65807
CCOP - Montana Cancer Consortium Billings, Montana  59101
Newark Beth Israel Medical Center Newark, New Jersey  07112
CCOP - Columbus Columbus, Ohio  43206
CCOP - Dayton Kettering, Ohio  45429
Lehigh Valley Hospital Allentown, Pennsylvania  18103
Albert Einstein Cancer Center Philadelphia, Pennsylvania  19141
Reading Hospital and Medical Center Reading, Pennsylvania  19612-6052
Mercy Hospital Cancer Center - Scranton Scranton, Pennsylvania  18501
CCOP - MainLine Health Wynnewood, Pennsylvania  19096
CCOP - Greenville Greenville, South Carolina  29615
Joe Arrington Cancer Research and Treatment Center Lubbock, Texas  79410-1894
Green Mountain Oncology Group Rutland, Vermont  05701
Massey Cancer Center Richmond, Virginia  23298-0037
St. Vincent Hospital Green Bay, Wisconsin  54307-3508
CCOP - Evanston Evanston, Illinois  60201
CCOP - Northern Indiana CR Consortium South Bend, Indiana  46601
CCOP - Grand Rapids Grand Rapids, Michigan  49503
MBCCOP - University of New Mexico HSC Albuquerque, New Mexico  87131
CCOP - Columbia River Oncology Program Portland, Oregon  97225
CCOP - Scott and White Hospital Temple, Texas  76508
CCOP - Marshfield Medical Research and Education Foundation Marshfield, Wisconsin  54449
Baptist Regional Cancer Institute - Jacksonville Jacksonville, Florida  32207
University of Arkansas for Medical Sciences Little Rock, Arkansas  72205
Dwight David Eisenhower Army Medical Center Fort Gordon, Georgia  30905-5650
Boston Medical Center Boston, Massachusetts  02118
Providence Hospital - Southfield Southfield, Michigan  48075-9975
CCOP - St. Louis-Cape Girardeau Saint Louis, Missouri  63141
CCOP - Virginia Mason Research Center Seattle, Washington  98101
CCOP - Northwest Tacoma, Washington  98405-0986
Puget Sound Oncology Consortium Seattle, Washington  98109
Sutter Cancer Center Sacramento, California  95816
Kaiser Permanente Medical Center - Vallejo Vallejo, California  94589
Hartford Hospital Hartford, Connecticut  06102-5037
Illinois Masonic Medical Center Chicago, Illinois  60657
West Suburban Hospital Medical Center Oak Park, Illinois  60302
Holden Comprehensive Cancer Center Iowa City, Iowa  52242-1009
Lucille Parker Markey Cancer Center, University of Kentucky Lexington, Kentucky  40536-0093
Norton Healthcare System Louisville, Kentucky  40202-5070
Louisiana State University Medical Center - New Orleans New Orleans, Louisiana  70112
Eastern Maine Medical Center Bangor, Maine  04401
Franklin Square Hospital Center Baltimore, Maryland  21237
Lahey Clinic - Burlington Burlington, Massachusetts  01805
Berkshire Medical Center Pittsfield, Massachusetts  01201
Baystate Medical Center Springfield, Massachusetts  01199
Michigan State University East Lansing, Michigan  48824
Staten Island University Hospital Staten Island, New York  10305
CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C. Syracuse, New York  13217
Aultman Cancer Center Canton, Ohio  44710
Jewish Hospital of Cincinnati, Inc. Cincinnati, Ohio  45236
CCOP - Oklahoma Tulsa, Oklahoma  74136
Allegheny General Hospital Pittsburgh, Pennsylvania  15212-4772
Utah Valley Regional Medical Center - Provo Provo, Utah  84604
Virginia Oncology Associates - Newport News Newport News, Virginia  23606
Eastern Virginia Medical School Norfolk, Virginia  23507
Oncology and Hematology Associates of Southwest Virginia, Inc. Roanoke, Virginia  24014
Camden-Clark Memorial Hospital Parkersburg, West Virginia  26102
Comprehensive Cancer Institute of Huntsville Huntsville, Alabama  35801
William Beaumont Hospital Royal Oak, Michigan  48073
Cancer Institute of New Jersey New Brunswick, New Jersey  08901
Rebecca and John Moores UCSD Cancer Center La Jolla, California  92093-0658
Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego San Diego, California  92120
City of Hope Comprehensive Cancer Center Duarte, California  91010
CCOP - Colorado Cancer Research Program, Incorporated Denver, Colorado  80224
Thompson Cancer Survival Center Knoxville, Tennessee  37916
Comprehensive Cancer Centers of the Desert Palm Springs, California  92262
North Idaho Cancer Center Coeur d'Alene, Idaho  83814
Clarian Health Partners Inc. Indianapolis, Indiana  46206-1367
Methodist Hospital Cancer Center - Omaha Omaha, Nebraska  68114
Barrett Cancer Center Cincinnati, Ohio  45267-0502
CCOP - Toledo Community Hospital Toledo, Ohio  43623-3456
York Cancer Center York, Pennsylvania  17403
Emory University School of Medicine Atlanta, Georgia  30322
MBCCOP-Our Lady of Mercy Cancer Center Bronx, New York  10466
Abbott-Northwestern Hospital Minneapolis, Minnesota  55407
Pacific Shores Medical Group Long Beach, California  90813
Genesis Medical Center Davenport, Iowa  52804
Morton Plant Hospital Clearwater, Florida  33756
Consultants in Blood Disorders and Cancer Louisville, Kentucky  40207
Tulane University Medical Center New Orleans, Louisiana  70112
Lincoln Medical and Mental Health Center Bronx, New York  10451
Alamance Cancer Center Burlington, North Carolina  27216
South Pointe Hospital - Cancer Care Center Warrensville Heights, Ohio  44122
Camcare Health Charleston, West Virginia  25304
Alexian Brothers Medical Center Elk Grove Village, Illinois  60007
Loma Linda University Cancer Institute Loma Linda, California  92354
Cancer Research Network Inc. Plantation, Florida  33324
Medical College of Georgia Augusta, Georgia  30912
Center for Oncology Research and Treatment, Medical City Hospital Dallas, Texas  75230
Scripps Cancer Center La Jolla, California  92037
Illinois Oncology, Ltd. Belleville, Illinois  62221
University of Connecticut Farmington, Connecticut  06032
Oncology Hematology Consultants Sarasota, Florida  34239
Cancer Center of Hawaii Honolulu, Hawaii  96826
Henry Ford Health System Detroit, Michigan  48202
New York Oncology Hematology, P.C. Albany, New York  12208
Glens Falls Hospital Glens Falls, New York  12801