Trial Information

A Randomised, Double-Blind Trial to Assess the Effects on Bone Mineral Density and Bone Biomarkers of Anastrozole When Used to Prevent Breast Cancer in Postmenopausal Women

OBJECTIVES:

Primary

- Compare the changes in bone of the spine and femur in postmenopausal women with ductal
carcinoma in situ treated with anastrozole vs placebo on protocol CRUK-IBIS-II-DCIS.

- Determine the effect of bisphosphonate treatment on bone mineral density and bone
metabolism in patients who are receiving anastrozole on protocol CRUK-IBIS-II-DCIS and
are osteoporotic or moderately to severely osteopenic at baseline.

Secondary

- Correlate changes in levels of biochemical markers of bone metabolism with longer-term
changes in bone mineral density, as measured by dual-energy x-ray absorptiometry (DXA).

OUTLINE: This is a multicenter, partially randomized, double-blind study. Patients are
stratified according to bone mineral density (T-score) measurements (≥ -1.5 vs -2.5 to <
-1.5 vs -4.0 to < -2.5 or ≤ 2 low-trauma vertebral fractures). Patients in stratum I are
further stratified according to calcium and cholecalciferol (vitamin D) supplementation (yes
vs no) and use of risedronate on this study (yes vs no). Patients in stratum II are further
stratified according to randomized treatment on protocol CRUK-IBIS-II-DCIS (yes vs no).

- Stratum I (T-score ≥ -1.5): Patients undergo dual-energy x-ray absorptiometry (DXA)
scanning at baseline and then at 1, 3, 5, and 7 years. Patients who develop
osteoporosis (T-score < -2.5) are removed from the study and receive open-label
bisphosphonates.

- Stratum II (T-score -2.5 to < -1.5 [moderate to severe osteopenia]): Patients undergo
DXA scanning as in stratum I. Patients are also randomized (double-blind) to 1 of 2
treatment arms.

- Arm I: Patients receive oral risedronate once a week for 5 years.

- Arm II: Patients receive oral placebo once a week for 5 years. Patients in either
arm who develop osteoporosis AND a drop in T-score of more than 1 unit are removed
from the study and receive open-label bisphosphonates.

- Stratum III (T-score -4.0 to < -2.5 OR ≤ 2 low trauma vertebral fractures
[osteoporosis]): Patients undergo DXA scanning as in stratum I. Patients also receive
oral risedronate (or their current bisphosphonate) once a week for 5 years.

Blood samples for correlative studies (e.g., bone biomarkers, serum estradiol) are collected
at baseline and at 6 and 12 months.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 1,000 patients will be accrued for this study.