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

Sponsor

Herbert Irving Comprehensive Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00049452

Collaborator

National Cancer Institute (NCI) (NIH)

120

Enrollment

Locations

Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Osteoporosis	Drug: zoledronic acid	Phase 3

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Masking:

Double

Primary Purpose:

Supportive Care

Official Title:

A Randomized, Placebo Controlled Trial Of Zoledronic Acid For The Prevention Of Bone Loss In Premenopausal Women With Early Stage Breast Cancer

Study Start Date :

Dec 1, 2001

Actual Study Completion Date :

Aug 1, 2008

Outcome Measures

Primary Outcome Measures

Changes in lumbar spine bone mineral density (BMD) at 6 months []

Secondary Outcome Measures

Changes in lumbar spine BMD at 12 and 24 months []
Total hip and femoral neck BMD at 6, 12, and 24 months []
Serum markers of bone turnover (osteocalcin, bone-specific alkaline phosphatase, and cross-linked C-telopeptide of type 1 collagen levels) measured every 6 weeks for 6 months, and at 9 and 12 months []
Quality of life as measured by the Short Form-36 instrument at baseline, and at 6 and 12 months []
Treatment costs []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Carl and Dorothy Bennett Cancer Center at Stamford Hospital	Stamford	Connecticut	United States	06904
2	Valley Hospital - Paramus	Paramus	New Jersey	United States	07652-2509
3	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York	United States	10032