A randomized phase III trial of exemestane versus anastrozole in postmenopausal women with receptor positive primary breast cancer - MA.27

Phase 1

• Conditions: Post-menopausal women, histologically or cytologically confirmed, receptor-positive,adequately excised, primary breast cancer

• Registration Number: EUCTR2005-001893-28-BE
• Lead Sponsor: International Breast Cancer Study Group (IBCSG)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-12-21
• Last Update Posted: 21 August 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 5800

Inclusion Criteria

Patients must have completely resected and histologically confirmed invasive breast cancer in the following TNM categories (AJCC Version 6): pT1, pT2 or pT3; pNx, pN0, pN1, pN2 or, only when the sole basis for this classification is the presence of 10 or more involved axillary nodes, pN3; M0. Surgical margins must be clear of invasive carcinoma and DCIS/LCIS. Patients with positive sentinel node biopsies must have subsequent axillary dissection to be eligible; negative sentinel node biopsies require no more axillary surgery for eligibility.

The primary tumour must be receptor-positive i.e. ER and/or PgR positive (defined as a tumour receptor content of > 10 fmol/mg protein, or receptor positive by immunohistochemistry: ERICA or PgRICA)

Postmenopausal status, prior to chemotherapy

Patients with bilateral breast cancers are eligible only if their cancers are synchronous (diagnosed at the same time). One or both tumours need to have receptor positive markers. One could be negative.

Patients must have had a bilateral mammogram within 12 months prior to randomization, unless the initial surgery was a total mastectomy, in which case only a mammogram of the remaining breast is required.

Radiologic investigations (bone scan, abdominal ultrasound or CT abdomen, chest x-ray) must be negative for metastases

Patients must be randomized a minimum of 3 weeks and a maximum of 3 months after completion of chemotherapy. If no chemotherapy is given, patients must be enrolled no less than 3 weeks and no later than 3 months after primary surgery.

Minimum life expectancy of 5 years.

Hematology: WBC > 3.0 x 109/L or granulocytes (polymorphs + bands) > 1.5 x 109/L; platelets > 100 x 109/L within 4 weeks prior to randomization.

Biochemistry: AST (SGOT) and/or ALT (SGPT) and alkaline phosphatase< 2 x the upper limit of institutional normal (UNL) unless imaging examinations have ruled out metastatic disease. Creatinine < 1.5 X UNL within 4 weeks prior to randomization.

ECOG Performance Status 0, 1, or 2

Patient must be able to swallow study medication and have adequate unassisted oral intake to maintain a reasonable state of nutrition.

Patients must be accessible for treatment and follow-up.

Patient consent must be obtained according to local Institutional and/or University Human Experimentation Committee requirements.

Protocol therapy must begin within 10 working days of randomization
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Premenopausal status (premenopausal women excluded because aromatase inhibitors are not employed in this group as monotherapy).

Patients with only receptor negative primary tumours.

Patients with metachronous breast cancer (breast cancers diagnosed at different times).

Less than 3 weeks or more than 3 months have elapsed since completion of chemotherapy; if no chemotherapy, less than 3 weeks or more than 3 months have elapsed since primary surgery.

Patients with locally recurrent or metastatic breast cancer

Patients with a history of other (non-breast) malignancies, except: adequately treated nonmelanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for > 5 years.

Patients receiving concurrent hormonal therapy with estrogens, progesterones or androgens, or any selective estrogen receptor modulator (SERM). Vaginal atrophy refractory to local measures may be treated, at the discretion of the investigator, with intermittent vaginal estrogens.

Patients having received prior treatment with a recognized aromatase inhibitor.

Any co-existing medical or psychiatric condition that is likely to interfere with study procedures and/or results.

Prior treatment on a trial for breast cancer if permission has not been obtained from the sponsors of the original study for the patient to participate in MA.27. (MA.20 patients may participate in MA.27. MA.21 patients may not participate in MA.27.)

Any prior treatment with tamoxifen or SERMs other than raloxifene. (Previous use of raloxifene is permitted, but the patient must have been off raloxifene for 3 weeks prior to randomization.) Any prior treatment with hormones or steroids (including over-the-counter products and supplements considered to have an estrogenic effect if not discontinued at least 3weeks prior to randomization

Patients with a prior diagnosis of in situ carcinoma in the contralateral breast treated with partial mastectomy and/or hormonal therapy

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare event free survival (EFS) between postmenopausal women treated with exemestane or anastrozole as adjuvant therapy.<br>;Secondary Objective: To compare overall survival (OS) of postmenopausal women treated with exemestane with that of those receiving anastrozole as adjuvant therapy.<br><br>To compare the time to distant recurrence for postmenopausal women treated with exemestane with that for women receiving anastrozole as adjuvant therapy.<br><br>To compare the incidence of new primary contralateral breast cancer in the different treatment groups.<br><br>To compare the incidence of all clinical fractures and specifically hip and vertebral fractures in the different treatment groups. <br><br>To compare cardiovascular morbidity and mortality between exemestane and anastrozole.;Primary end point(s): Event free survival, 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.