Effectiveness of Zoledronic Acid in the Prevention of Osteoporosis in Early Breast Cancer Patients Receiving Letrozole

August 22, 2011 updated by: David B. Geffen, Soroka University Medical Center

Phase 3 Study of the Effect of Zoledronic Acid in the Prevention of Osteoporosis in Early Breast Cancer Patients Receiving the Aromatase Inhibitor, Letrozole, in the Adjuvant Setting

The purpose of this study is to determine whether zoledronic acid given intravenously every 6 months can prevent reduction in bone mineral density in women with early stage breast cancer receiving adjuvant therapy with the aromatase inhibitor drug letrozole, after having received adjuvant tamoxifen.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Letrozole is an aromatase inhibitor used in the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women.It has more recently been approved for use in many countries as adjuvant therapy for early breast cancer; and is often used in an adjuvant regimen following 2-3 years of tamoxifen treatment or as an extended adjuvant therapy after up to 5 years of tamoxifen. Letrozole inhibits the conversion of androgens to estrogens in vitro and in vivo. Plasma levels of estradiol and related estrogen compounds in postmenopausal patients receiving letrozole are suppressed up to 95% from baseline and are often undetectable.The estrogen deprivation in women receiving letrozole may cause increased bone resorption and bone loss.Studies comparing tamoxifen and aromatase inhibitors, in adjuvant therapy have shown an increase fracture rate, and decreased bone mineral density in patients receiving aromatase inhibitors. Zoledronic acid is an intravenously administered bisphosphonate that inhibits osteoclastic bone resorption. Intravenous bisphosphonates are effective in reducing the rate of skeletal complications, including fractures, in patients with metastatic breast cancer and other tumors when given every few weeks. Small clinical trials have given some evidence that osteoporosis can be effectively treated by one or two doses of intravenous zoledronic acid per year. This study will determine the effect of giving zoledronic acid every 6 months on the bone mineral density of patients receiving letrozole as adjuvant therapy for early breast cancer after having received adjuvant tamoxifen for at least 2.5 years. Patients will be randomized to receive zoledronic acid either at the start of letrozole therapy or when bone mineral density T score drops below - 2 standard deviation or at the occurrence of a non-trauma related fracture.

Study Type

Interventional

Enrollment (Actual)

90

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Beer Sheva, Israel
        • Soroka University Medical Center
      • Tel Aviv, Israel
        • Tel Aviv Sourasky Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Postmenopausal women with histologically documented early (non-metastatic) breast cancer
  • Previous treatment with tamoxifen for at least 2.5 years and not more than 3.5 years
  • Assigned to receive letrozole treatment
  • Karnofsky performance status ≥ 70
  • Life expectancy ≥ 16 weeks
  • Signed informed consent after full explanation of study by participating clinician and prio to any study specific procedures
  • Adjuvant or neoadjuvant chemotherapy is allowed
  • No clinical and/or radiologic evidence of distant metastases
  • No prior treatment with an aromatase inhibitor
  • Able to comply with treatment and scheduled follow-up visits
  • Age between 18 and 82 years

Exclusion Criteria:

  • Pregnant or lactating women or women with child bearing potential
  • Patients with other malignancies except except adequately treated basal cell carcinoma of the skin or in-situ cervix carcinoma
  • Active infection or other serious underlying medical condition which would impair the ability of the patient to receive protocol treatment
  • Clinical and/or radiological evidence of distant metastases.
  • Evidence of pathological fracture
  • Prior treatment with an aromatase inhibitor
  • Prior administration of any intravenous bisphosphonate during the last year.
  • Oral bisphosphonate must be discontinued within 4 weeks of enrollment
  • Administration of long-term systemic corticosteroids within the last 12 months (short term steroid treatment is allowed.)
  • Prior use of parathyroid hormone treatment for more than 1 week
  • Use of any drug known to affect the skeleton (calcitonin, mithramycin, gallium nitrate) within two weeks prior to enrollment
  • Abnormal renal function: creatinine clearance must be above 30 ml/min (calculated by Cockroft formula)
  • Evidence of metabolic bone disease( Paget's, osteogenesis imperfecta, hyperparathyroidism within the 12 months prior to enrollment)
  • Baseline lumbar spine and or total hip Bone Mineral Density T score below -2
  • Known hypersensitivity to zoledronic acid
  • Psychological, familial, sociologic, or geographic conditions which do not permit medical follow-up and compliance with the study protocol
  • White blood cell ≤ 3.0 x 10exp9 /L or granulocytes ≤ 1.5 x 10exp9/L or platelets ≤100 x 10exp9
  • Total bilirubin> 1.5 x upper normal limit, SGOT and SGPT > 2.5 x upper normal limit
  • Unable to undergo DXA bone density scanning (spine deformity, severe scoliosis, lumbar sacral spine surgery)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Immediate zoledronic acid
Patients on this arm will receive zoledronic acid every 6 months during 2.5 years of letrozole therapy starting within 3 months of the start of letrozole therapy. (5 doses of zoledronic acid)
Drug: zoledronic acid
Zoledronic acid 4 mg IV every 6 months up to 2.5 years after the start of letrozole treatment.
Other Names:
  • Zomera, zolendronate
Active Comparator: Delayed zoledronic acid
Patients on this arm will receive zoledronic acid during the 2.5 years of letrozole treatment only after the T-score on bone mineral density testing falls below minus 2.0.
Drug: zoledronic acid
Zoledronic acid 4 mg IV every 6 months up to 2.5 years after the start of letrozole treatment.
Other Names:
  • Zomera, zolendronate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
renal function
bone mineral density
bone events
liver function

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Soroka University Medical Center

Collaborators

Tel-Aviv Sourasky Medical Center

Investigators

  • Study Chair: Tamar Safra, M.D., Tel-Aviv Sourasky Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2005

Primary Completion (Actual)

November 1, 2010

Study Registration Dates

First Submitted

September 14, 2006

First Submitted That Met QC Criteria

September 14, 2006

First Posted (Estimate)

September 15, 2006

Study Record Updates

Last Update Posted (Estimate)

August 23, 2011

Last Update Submitted That Met QC Criteria

August 22, 2011

Last Verified

August 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • sor440006ctil

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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