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

This study has been completed.
Sponsor:
Collaborators:
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):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00066573
First received: August 6, 2003
Last updated: May 14, 2014
Last verified: May 2014
  Purpose

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.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Phase III Trial Of Exemestane Versus Anastrozole In Postmenopausal Women With Receptor Positive Primary Breast Cancer

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:
  • Event-free Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 8 years ] [ Designated as safety issue: No ]
  • Distant Disease-free Survival [ Time Frame: 8 years ] [ Designated as safety issue: No ]
  • New Primary Breast Cancer [ Time Frame: 8 years ] [ Designated as safety issue: No ]
  • Clinical Fracture Rate [ Time Frame: 8 years ] [ Designated as safety issue: No ]
  • Cardiovascular Morbidity and Mortality [ Time Frame: 8 years ] [ Designated as safety issue: No ]

Enrollment: 7576
Study Start Date: June 2003
Study Completion Date: March 2011
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral exemestane (25 mg) once daily for 5 years.
Drug: exemestane
Given orally
Active Comparator: Arm II
Patients receive oral anastrozole (1 mg) once daily for 5 years.
Drug: anastrozole
Given orally

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00066573

  Show 39 Study Locations
Sponsors and Collaborators
NCIC Clinical Trials Group
North Central Cancer Treatment Group
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
Southwest Oncology Group
International Breast Cancer Study Group
Investigators
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
  More Information

Publications:
Moy B, Elliott CR, Chapman J-AW, et al.: NCIC CTG MA.27: menopausal symptoms of ethnic minority women. [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-3059, S144, 2006.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00066573     History of Changes
Obsolete Identifiers: NCT00438529
Other Study ID Numbers: MA27, CAN-NCIC-MA27, NCCTG-MA27, CALGB-CAN-NCIC-MA27, ECOG-CAN-NCIC-MA27, SWOG-CAN-NCIC-MA27, IBCSG-30-04, EUDRACT-2005-001893-28, CDR0000316325
Study First Received: August 6, 2003
Results First Received: April 16, 2014
Last Updated: May 14, 2014
Health Authority: Canada: Health Canada
United States: Food and Drug Administration

Keywords provided by NCIC Clinical Trials Group:
stage IIIA breast cancer
stage I breast cancer
stage II breast cancer

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

ClinicalTrials.gov processed this record on August 28, 2014