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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00016432
• Other study ID #: NSABP B-33
• Secondary ID: CDR0000068640
• Status: Completed
• Phase: Phase 3
• First received: May 6, 2001
• Last updated: April 18, 2011
• Start date: May 2001
• Est. completion date: February 2011

Study information

• Verified date: April 2011
• Source: NSABP Foundation Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1598
• Est. completion date: February 2011
• Est. primary completion date: October 2003
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• exemestane
25 mg for 5 years
• Placebo
Placebo

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Center - Calgary	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Credit Valley Hospital	Mississauga	Ontario
Canada	Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	Jewish General Hospital - Montreal	Montreal	Quebec
Canada	Montreal General Hospital	Montreal	Quebec
Canada	Royal Victoria Hospital - Montreal	Montreal	Quebec
Canada	St. Mary's Hospital Center	Montreal	Quebec
Canada	Hopital du Saint-Sacrement, Quebec	Quebec City	Quebec
Canada	Toronto Sunnybrook Regional Cancer Centre	Toronto	Ontario
Canada	British Columbia Cancer Agency	Vancouver	British Columbia
Puerto Rico	MBCCOP - San Juan	San Juan
United States	Akron City Hospital	Akron	Ohio
United States	New York Oncology Hematology, P.C.	Albany	New York
United States	MBCCOP - University of New Mexico HSC	Albuquerque	New Mexico
United States	Lehigh Valley Hospital	Allentown	Pennsylvania
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Medical College of Georgia	Augusta	Georgia
United States	Franklin Square Hospital Center	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Illinois Oncology, Ltd.	Belleville	Illinois
United States	Green Mountain Oncology Group	Bennington	Vermont
United States	National Naval Medical Center	Bethesda	Maryland
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Boston Medical Center	Boston	Massachusetts
United States	Lincoln Medical and Mental Health Center	Bronx	New York
United States	MBCCOP-Our Lady of Mercy Cancer Center	Bronx	New York
United States	Alamance Cancer Center	Burlington	North Carolina
United States	Lahey Clinic - Burlington	Burlington	Massachusetts
United States	Vermont Cancer Center	Burlington	Vermont
United States	Aultman Cancer Center	Canton	Ohio
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
United States	Camcare Health	Charleston	West Virginia
United States	Illinois Masonic Medical Center	Chicago	Illinois
United States	Rush-Presbyterian-St. Luke's Medical Center	Chicago	Illinois
United States	Barrett Cancer Center	Cincinnati	Ohio
United States	Jewish Hospital of Cincinnati, Inc.	Cincinnati	Ohio
United States	Morton Plant Hospital	Clearwater	Florida
United States	Ireland Cancer Center	Cleveland	Ohio
United States	North Idaho Cancer Center	Coeur d'Alene	Idaho
United States	Ellis Fischel Cancer Center - Columbia	Columbia	Missouri
United States	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	Center for Oncology Research and Treatment, Medical City Hospital	Dallas	Texas
United States	Simmons Cancer Center - Dallas	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Genesis Medical Center	Davenport	Iowa
United States	Halifax Medical Center	Daytona Beach	Florida
United States	CCOP - Central Illinois	Decatur	Illinois
United States	CCOP - Colorado Cancer Research Program, Incorporated	Denver	Colorado
United States	University of Colorado Cancer Center	Denver	Colorado
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	Henry Ford Health System	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	CCOP - Duluth	Duluth	Minnesota
United States	Michigan State University	East Lansing	Michigan
United States	Alexian Brothers Medical Center	Elk Grove Village	Illinois
United States	CCOP - Evanston	Evanston	Illinois
United States	CCOP - Merit Care Hospital	Fargo	North Dakota
United States	University of Connecticut	Farmington	Connecticut
United States	Dwight David Eisenhower Army Medical Center	Fort Gordon	Georgia
United States	California Cancer Center	Fresno	California
United States	Glens Falls Hospital	Glens Falls	New York
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	St. Vincent Hospital	Green Bay	Wisconsin
United States	Sutter Health Western Division Cancer Research Group	Greenbrae	California
United States	CCOP - Greenville	Greenville	South Carolina
United States	East Carolina University School of Medicine	Greenville	North Carolina
United States	CCOP - Northern New Jersey	Hackensack	New Jersey
United States	Hartford Hospital	Hartford	Connecticut
United States	Cancer Center of Hawaii	Honolulu	Hawaii
United States	Baylor College of Medicine	Houston	Texas
United States	Comprehensive Cancer Institute of Huntsville	Huntsville	Alabama
United States	Clarian Health Partners Inc.	Indianapolis	Indiana
United States	St. Vincent Hospital and Health Care Center	Indianapolis	Indiana
United States	Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Baptist Regional Cancer Institute - Jacksonville	Jacksonville	Florida
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	CCOP - Kansas City	Kansas City	Missouri
United States	CCOP - Dayton	Kettering	Ohio
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	Scripps Cancer Center	La Jolla	California
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Lucille Parker Markey Cancer Center, University of Kentucky	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Loma Linda University Cancer Institute	Loma Linda	California
United States	Pacific Shores Medical Group	Long Beach	California
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	Consultants in Blood Disorders and Cancer	Louisville	Kentucky
United States	Norton Healthcare System	Louisville	Kentucky
United States	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	CCOP - Marshfield Medical Research and Education Foundation	Marshfield	Wisconsin
United States	Sylvester Cancer Center, University of Miami	Miami	Florida
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	Louisiana State University Medical Center - New Orleans	New Orleans	Louisiana
United States	Tulane University Medical Center	New Orleans	Louisiana
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Virginia Oncology Associates - Newport News	Newport News	Virginia
United States	Eastern Virginia Medical School	Norfolk	Virginia
United States	West Suburban Hospital Medical Center	Oak Park	Illinois
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Methodist Hospital Cancer Center - Omaha	Omaha	Nebraska
United States	Chao Family Comprehensive Cancer Center	Orange	California
United States	MD Anderson Cancer Center Orlando	Orlando	Florida
United States	Comprehensive Cancer Centers of the Desert	Palm Springs	California
United States	Camden-Clark Memorial Hospital	Parkersburg	West Virginia
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Albert Einstein Cancer Center	Philadelphia	Pennsylvania
United States	Kimmel Cancer Center of Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	CCOP - Greater Phoenix	Phoenix	Arizona
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	Berkshire Medical Center	Pittsfield	Massachusetts
United States	Cancer Research Network Inc.	Plantation	Florida
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Utah Valley Regional Medical Center - Provo	Provo	Utah
United States	Reading Hospital and Medical Center	Reading	Pennsylvania
United States	Massey Cancer Center	Richmond	Virginia
United States	Oncology and Hematology Associates of Southwest Virginia, Inc.	Roanoke	Virginia
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	Sutter Cancer Center	Sacramento	California
United States	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri
United States	St. Louis University Health Sciences Center	Saint Louis	Missouri
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego	San Diego	California
United States	CCOP - Santa Rosa Memorial Hospital	Santa Rosa	California
United States	Oncology Hematology Consultants	Sarasota	Florida
United States	Mercy Hospital Cancer Center - Scranton	Scranton	Pennsylvania
United States	CCOP - Virginia Mason Research Center	Seattle	Washington
United States	Puget Sound Oncology Consortium	Seattle	Washington
United States	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Providence Hospital - Southfield	Southfield	Michigan
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Baystate Medical Center	Springfield	Massachusetts
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	Stanford University Medical Center	Stanford	California
United States	Staten Island University Hospital	Staten Island	New York
United States	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	Syracuse	New York
United States	CCOP - Northwest	Tacoma	Washington
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	CCOP - Oklahoma	Tulsa	Oklahoma
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Kaiser Permanente Medical Center - Vallejo	Vallejo	California
United States	South Pointe Hospital - Cancer Care Center	Warrensville Heights	Ohio
United States	George Washington University Medical Center	Washington	District of Columbia
United States	CCOP - Wichita	Wichita	Kansas
United States	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina
United States	CCOP - MainLine Health	Wynnewood	Pennsylvania
United States	York Cancer Center	York	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
NSABP Foundation Inc	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico, 

References & Publications (2)

Mamounas E, Jeong J-H, Wickerham L, et al.: Benefit from exemestane (EXE) as extended adjuvant therapy after 5 years of tamoxifen (TAM): intent-to-treat analysis of NSABP B-33. [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-49, S22, 2006.

Mamounas EP, Jeong JH, Wickerham DL, Smith RE, Ganz PA, Land SR, Eisen A, Fehrenbacher L, Farrar WB, Atkins JN, Pajon ER, Vogel VG, Kroener JF, Hutchins LF, Robidoux A, Hoehn JL, Ingle JN, Geyer CE Jr, Costantino JP, Wolmark N. Benefit from exemestane as — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival		Every 12 months until breast cancer recurrence, second primary cancer or death from any cause.	No
Secondary	Overall survival		Death from any cause	No
Secondary	Time to treatment failure		time from randomization to recurrence or contralateral second primary cancer	No
Secondary	Bone measure as measured by total alkaline phosphatase, fracture history, and height measurement		measurements taken at regular intervals from randomization through 6 years following randomiztion	Yes