Zoledronate in Preventing Bone Loss in Premenopausal Women Receiving Chemotherapy After Surgery For Early Stage Breast Cancer

Herbert Irving Comprehensive Cancer Center

Status and phase: Completed; Phase 3

Conditions: Osteoporosis; Breast Cancer

Treatments: Drug: zoledronic acid

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00049452

CPMC-IRB-14069

NOVARTIS-CPMC-IRB-14069

NCI-G02-2127

CDR0000258105

Details and patient eligibility

About

RATIONALE: It is not yet known whether zoledronate is effective in preventing bone loss in premenopausal women who are receiving adjuvant chemotherapy after undergoing surgery for early stage breast cancer.

PURPOSE: Randomized phase III trial to determine the effectiveness of zoledronate in preventing bone loss in premenopausal women who are receiving chemotherapy after surgery for early stage breast cancer.

Full description

OBJECTIVES:

• Compare the changes in bone mineral density (BMD) and bone turnover that occur in premenopausal women with resected early stage breast cancer during and after 6 months of adjuvant chemotherapy.
• Determine the factors that predict bone loss during chemotherapy, particularly induction of amenorrhea, type of chemotherapeutic regimen, glucocorticoid exposure, and baseline BMD, in these patients.
• Determine whether zoledronate prevents bone loss in these patients when given during and after adjuvant chemotherapy.
• Determine the effect of zoledronate on markers of bone turnover in these patients during and after adjuvant chemotherapy.
• Determine whether the effect on markers of bone turnover predicts response to zoledronate in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to estrogen receptor status (positive vs negative), progesterone receptor status (positive vs negative), and adjuvant chemotherapy regimen. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive zoledronate IV over 15 minutes on day 1.
• Arm II: Patients receive placebo IV over 15 minutes on day 1. In both arms, treatment repeats every 3 months for up to 4 courses in the absence of disease progression. Patients also receive calcium and cholecalciferol (vitamin D) supplements daily.

Quality of life is assessed at baseline and at 6 and 12 months.

Patients are followed at 1 year.

PROJECTED ACCRUAL: A total of 120 patients (60 per treatment arm) will be accrued for this study.

Enrollment: 120 estimated patients

Sex: Female

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Diagnosis of localized breast cancer

  • Stage I or II (T1-3, N0-2, M0)

• Planned adjuvant chemotherapy (after surgery) of at least 6 months in duration

• Hormone receptor status:

  • Estrogen receptor and progesterone receptor status known

PATIENT CHARACTERISTICS:

Age

• 18 to 50

Sex

• Female

Menopausal status

• Premenopausal or perimenopausal

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Creatinine less than 2 mg/dL

Other

• No T score of less than 2.0 on bone mineral density (BMD)
• No fragility fracture
• No lumbar spine anatomy that would preclude accurate BMD measurement of a minimum of 3 lumbar vertebrae
• Not pregnant

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• No concurrent radiotherapy

Surgery

• See Disease Characteristics

Other

• At least 1 month since prior calcitonin
• At least 12 months since prior bisphosphonates given for more than 1 month duration
• No concurrent fluoride therapy (10 mg/day or more)
• No concurrent enrollment in another experimental drug study