Conditions: Breast Cancer
Keywords: stage IV breast cancer recurrent breast cancer
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 695
Healthy volunteers: no

Brief summary:
RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using drugs such as anastrozole and fulvestrant may fight breast cancer by blocking the use of estrogen. It is not yet known whether anastrozole is more effective with or without fulvestrant in treating breast cancer.

PURPOSE: This randomized phase III trial is studying giving anastrozole together with fulvestrant to see how well it works compared to anastrozole alone as first-line therapy in treating postmenopausal women with metastatic breast cancer.

Detailed description:
OBJECTIVES:

* Compare the time to tumor progression in postmenopausal women with metastatic breast cancer treated with anastrozole with or without fulvestrant as first-line therapy.
* Compare the clinical benefit (complete or partial response, confirmed or unconfirmed, or stable disease ≥ 24 weeks) and overall survival of patients treated with these regimens.
* Compare adverse events in patients treated with these regimens.
* Determine the prognostic significance of estrogen receptor positivity and HER2/neu status in patients treated with these regimens.
* Determine parameters of estrogen and clinical pharmacology and estrogen levels in patients treated with these regimens.
* Compare anastrozole plasma levels at 8, 16, and 24 weeks in patients treated with these regimens (closed as of 4/16/2009).
* Compare estradiol serum levels at 8, 16, and 24 weeks in patients treated with these regimens (closed as of 4/16/2009).

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior adjuvant tamoxifen therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive oral anastrozole once daily on days 1-28.
* Arm II: Patients receive oral anastrozole as in arm I. Patients also receive fulvestrant intramuscularly on days 1, 14, and 28 during course 1 and then on day 28 of the subsequent courses.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed for up to 4 years.

PROJECTED ACCRUAL: A total of 690 patients (345 per treatment arm) will be accrued for this study within 3 years.

Arms:
arm 1: Patients receive oral anastrozole once daily on days 1-28. arm 2: Patients receive oral anastrozole as in arm I. Patients also receive fulvestrant intramuscularly on days 1, 14, and 28 during course 1 and then on day 28 of the subsequent courses.

Interventions: intervention 1: anastrozole intervention 2: fulvestrant
Intervention descriptions: intervention 1: Given orally intervention 2: Given intramuscularly

Protocol document: