Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Supportive care	Closed	18 to 50	NCI, Pharmaceutical / Industry	CPMC-IRB-14069 NCI-G02-2127, NOVARTIS-CPMC-IRB-14069, NCT00049452

Objectives

1. 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.
2. 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.
3. Determine whether zoledronate prevents bone loss in these patients when given during and after adjuvant chemotherapy.
4. Determine the effect of zoledronate on markers of bone turnover in these patients during and after adjuvant chemotherapy.
5. Determine whether the effect on markers of bone turnover predicts response to zoledronate in these patients.

Entry 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

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

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

Expected Enrollment

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

Outcomes

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

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

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.

Hershman DL, McMahon DJ, Crew KD, et al.: Zoledronic acid prevents bone loss in premenopausal women undergoing adjuvant chemotherapy for early-stage breast cancer. J Clin Oncol 26 (29): 4739-45, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

Dawn Hershman, MD, Protocol chair		Ph: 212-305-1945

Registry Information
Official Title		A Randomized, Placebo Controlled Trial Of Zoledronic Acid For The Prevention Of Bone Loss In Premenopausal Women With Early Stage Breast Cancer
Trial Start Date		2001-12-31
Registered in ClinicalTrials.gov		NCT00049452
Date Submitted to PDQ		2002-09-16
Information Last Verified		2007-04-09
NCI Grant/Contract Number		CA13696

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