Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Exemestane or Anastrozole in Treating Postmenopausal Women Who Have Undergone Surgery for Primary Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00066573
Recruitment Status : Completed
First Posted : August 7, 2003
Results First Posted : May 15, 2014
Last Update Posted : April 8, 2020
Sponsor:
Collaborators:
National Cancer Institute (NCI)
North Central Cancer Treatment Group
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
Southwest Oncology Group
International Breast Cancer Study Group
Information provided by (Responsible Party):
Canadian Cancer Trials Group ( NCIC Clinical Trials Group )

Tracking Information
First Submitted Date  ICMJE August 6, 2003
First Posted Date  ICMJE August 7, 2003
Results First Submitted Date  ICMJE April 16, 2014
Results First Posted Date  ICMJE May 15, 2014
Last Update Posted Date April 8, 2020
Actual Study Start Date  ICMJE June 2, 2003
Actual Primary Completion Date November 7, 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 14, 2014)
Event-free Survival [ Time Frame: 5 years ]
Event free survival, the primary endpoint of this study, is defined as the time from randomization to the time of documented locoregional or distant recurrence, new primary breast cancer, or death from any cause.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2018)
  • Overall Survival: Percentage of Participants Alive at 5 Years [ Time Frame: 5 years ]
    Overall survival is defined as the time from randomization to the time of death from any cause.
  • Distant Disease-free Survival: Number of Participants Without Documented Distant Recurrence [ Time Frame: 5 years ]
    Time to distant disease-free survival (DDFS) is defined as the time from randomization to the time of documented distant recurrence. Distant recurrence is the cancer coming back in a part of the body away from the breast, such as the bones or liver.
  • Clinical Fracture Rate: Number of Participants With Bone Fractures. [ Time Frame: 8 years ]
    Clinical fracture at any time, including hip, spine, wrist fractures and other bone fractures.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Exemestane or Anastrozole in Treating Postmenopausal Women Who Have Undergone Surgery for Primary Breast Cancer
Official Title  ICMJE A Randomized Phase III Trial Of Exemestane Versus Anastrozole In Postmenopausal Women With Receptor Positive Primary Breast Cancer
Brief Summary

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

PURPOSE: This randomized phase III trial is studying exemestane to see how well it works compared to anastrozole in preventing cancer recurrence in postmenopausal women who have undergone surgery for primary breast cancer.

Detailed Description

OBJECTIVES:

Primary

  • Compare the event-free survival of postmenopausal women with receptor-positive primary breast cancer when treated with exemestane vs anastrozole.

Secondary

  • Compare the overall survival of patients treated with these regimens.
  • Compare the time to distant recurrence in patients treated with these regimens.
  • Compare the incidence of new primary contralateral breast cancer in patients treated with these regimens.
  • Compare the incidence of all clinical fractures, specifically hip and vertebral fractures, in patients treated with these regimens.
  • Compare cardiovascular morbidity and mortality (i.e., significant coronary heart disease, which includes myocardial infarctions and angina requiring percutaneous transluminal coronary angioplasty or coronary artery bypass graft, fatal and nonfatal strokes, and all vascular deaths) in patients treated with these regimens.
  • Correlate therapy induced changes in breast density with plasma hormones and growth factors, drug levels of exemestane and anastrozole, genetic variation and breast cancer recurrence or contralateral events in patients treated with these regimens.
  • Compare the toxic effects of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to lymph node status at diagnosis (negative vs positive vs unknown), prior adjuvant chemotherapy (yes vs no), and herceptin use (yes vs no). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral exemestane (25 mg) once daily for 5 years.
  • Arm II: Patients receive oral anastrozole (1 mg) once daily for 5 years. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 6 months during the first year of study participation and annually thereafter.

PROJECTED ACCRUAL: A total of 6,840 patients will be accrued for this study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: anastrozole
    Given orally
  • Drug: exemestane
    Given orally
Study Arms  ICMJE
  • Experimental: Exemestane
    Patients receive oral exemestane (25 mg) once daily for 5 years.
    Intervention: Drug: exemestane
  • Active Comparator: Anastrozole
    Patients receive oral anastrozole (1 mg) once daily for 5 years.
    Intervention: Drug: anastrozole
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 22, 2011)
7576
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE January 6, 2012
Actual Primary Completion Date November 7, 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Histologically confirmed invasive breast cancer

    • pT1-3; pNX, pN0-2 or pN3*; M0
    • Neoadjuvant patients are eligible no earlier than 3 weeks or later than 3 months after excisional surgery, provided both the clinical-diagnostic staging of cancer and postsurgical resection-pathologic staging of cancer meet the requirements for primary tumor, regional lymph nodes, and distant metastasis classification NOTE: *Only when the sole basis for this classification is the presence of 10 or more involved axillary lymph nodes
  • Completely resected disease

    • Primary surgery performed at least 3 weeks but no more than 3 months before study entry (if no chemotherapy was given)

      • Primary surgery is defined as the last surgery at which histologic evidence of invasive or in situ disease was present in the pathology specimen
    • Patients with positive sentinel lymph node biopsy are eligible provided they have had a subsequent axillary lymph node dissection
  • No metachronous breast cancer
  • Bilateral mammogram within the past 12 months unless initial surgery was a total mastectomy, in which case only a mammogram of the remaining breast is required
  • No metastases confirmed by 1 of the following methods:

    • Bone scan* (required only if alkaline phosphatase is at least 2 times normal and/or there are symptoms of metastatic disease)
    • Abdominal ultrasound or CT scan (required only if AST/ALT or alkaline phosphatase is at least 2 times normal, unless the elevation is in the bone fraction)
    • Chest x-ray NOTE: *Confirmatory x-ray, CT scan, or MRI required if the bone scan results are questionable
  • No locally recurrent disease
  • No prior or concurrent carcinoma in situ of the contralateral breast treated with partial mastectomy and/or hormonal therapy

    • Patients with prior or concurrent carcinoma in situ of the ipsilateral breast are eligible provided the tumor was completely excised AND they have not received prior hormonal therapy
  • Hormone receptor status:

    • Estrogen receptor- and/or progesterone receptor-positive by immunohistochemistry or tumor receptor content ≥ 10 fmol/mg protein

PATIENT CHARACTERISTICS:

Age

  • Postmenopausal

Sex

  • Female

Menopausal status

  • Postmenopausal prior to chemotherapy, defined as 1 of the following:

    • Over 60 years of age
    • Age 45-59 with spontaneous cessation of menses for more than 1 year prior to study entry
    • Age 45-59 with menses ceasing (secondary to hysterectomy or spontaneously) within the past year AND a follicle-stimulating hormone (FSH) level prior to study entry in the postmenopausal range*
    • Age 45-59, previously on hormone replacement therapy (HRT) and have discontinued HRT upon diagnosis of this malignancy AND has an FSH level prior to study entry in the postmenopausal range*
    • Has undergone bilateral oophorectomy NOTE: *By institutional standards OR > 34.4 IU/L if institutional range is not available)

Performance status

  • ECOG 0-2

Life expectancy

  • At least 5 years

Hematopoietic

  • WBC at least 3,000/mm^3 OR
  • Granulocyte count at least 1,500/mm^3 AND
  • Platelet count at least 100,000/mm^3

Hepatic

  • See Disease Characteristics
  • AST and/or ALT less than 2 times upper limit of normal (ULN)*
  • Alkaline phosphatase less than 2 times ULN* NOTE: *Unless imaging examinations have ruled out metastatic disease

Renal

  • Not specified

Other

  • Able to swallow study medication and have adequate unassisted oral intake in order to maintain reasonable nutrition status
  • No other non-breast malignancy within the past 5 years except adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other curatively treated solid tumors with no evidence of disease for at least 5 years
  • No other concurrent medical or psychiatric condition that would preclude study participation and/or interfere with results

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Prior and concurrent trastuzumab (Herceptin®) allowed

Chemotherapy

  • See Disease Characteristics
  • At least 3 weeks but no more than 3 months since prior chemotherapy
  • Prior adjuvant chemotherapy allowed

Endocrine therapy

  • See Disease Characteristics
  • No prior aromatase inhibitor
  • No prior tamoxifen or other selective estrogen receptor modulators (SERMs) except raloxifene

    • At least 3 weeks since prior raloxifene
  • At least 3 weeks since prior and no concurrent over-the-counter products or supplements considered to have an estrogenic effect, including any of the following:

    • Ginseng
    • Ginkgo biloba
    • Black cohosh
    • Dong quai
    • Fortified soy supplements (e.g., phytoestrogen preparations)
  • At least 3 weeks since other prior hormonal therapy or steroids considered to have an estrogenic effect
  • No concurrent estrogens, progesterones, androgens, or SERMs

    • Concurrent intermittent vaginal estrogens (e.g., vagifem, estrogen vaginal cream, testosterone, estradiol vaginal gel, or Estring) allowed if other local measures for intractable vaginal atrophy are insufficient
  • No other concurrent therapy that would have an estrogenic effect, including endocrine therapy, hormonal therapy, or steroid therapy

Radiotherapy

  • See Disease Characteristics
  • Prior adjuvant radiotherapy allowed
  • Concurrent radiotherapy allowed

Surgery

  • See Disease Characteristics
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries Australia,   Hungary,   Italy,   Puerto Rico,   South Africa,   Switzerland,   United States
 
Administrative Information
NCT Number  ICMJE NCT00066573
Other Study ID Numbers  ICMJE MA27
CAN-NCIC-MA27 ( Other Identifier: Cancer.gov )
NCCTG-MA27 ( Other Identifier: NCCTG )
CALGB-CAN-NCIC-MA27 ( Other Identifier: CALGB )
ECOG-CAN-NCIC-MA27 ( Other Identifier: ECOG )
SWOG-CAN-NCIC-MA27 ( Other Identifier: SWOG )
IBCSG-30-04 ( Other Identifier: IBCSG )
2005-001893-28 ( EudraCT Number )
CDR0000316325 ( Other Identifier: PDQ )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Canadian Cancer Trials Group ( NCIC Clinical Trials Group )
Study Sponsor  ICMJE NCIC Clinical Trials Group
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • North Central Cancer Treatment Group
  • Cancer and Leukemia Group B
  • Eastern Cooperative Oncology Group
  • Southwest Oncology Group
  • International Breast Cancer Study Group
Investigators  ICMJE
Study Chair: Paul E. Goss, MD, PhD Massachusetts General Hospital
Study Chair: James N. Ingle, MD Mayo Clinic
Study Chair: Matthew J. Ellis, MD, PhD, FRCP Washington University Siteman Cancer Center
Study Chair: George W. Sledge, MD Indiana University Melvin and Bren Simon Cancer Center
Study Chair: George T. Budd, MD The Cleveland Clinic
Principal Investigator: Manuela Rabaglio, MD University Hospital Inselspital, Berne
PRS Account Canadian Cancer Trials Group
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP