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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00376740
Recruitment Status : Completed
First Posted : September 15, 2006
Last Update Posted : August 23, 2011
Sponsor:
Collaborator:
Tel-Aviv Sourasky Medical Center
Information provided by (Responsible Party):
David B. Geffen, Soroka University Medical Center

Tracking Information
First Submitted Date  ICMJE September 14, 2006
First Posted Date  ICMJE September 15, 2006
Last Update Posted Date August 23, 2011
Study Start Date  ICMJE September 2005
Actual Primary Completion Date November 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 14, 2006)
  • bone mineral density
  • bone events
  • renal function
  • liver function
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effectiveness of Zoledronic Acid in the Prevention of Osteoporosis in Early Breast Cancer Patients Receiving Letrozole
Official Title  ICMJE 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
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Breast Cancer
Intervention  ICMJE Drug: zoledronic acid
Zoledronic acid 4 mg IV every 6 months up to 2.5 years after the start of letrozole treatment.
Other Name: Zomera, zolendronate
Study Arms  ICMJE
  • 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)
    Intervention: Drug: zoledronic acid
  • 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.
    Intervention: Drug: zoledronic acid
Publications * Safra T, Bernstein-Molho R, Greenberg J, Pelles-Avraham S, Stephansky I, Sarid D, Inbar MJ, Stemmer SM, Geffen DB. The protective effect of zoledronic acid on bone loss in postmenopausal women with early breast cancer treated with sequential tamoxifen and letrozole: a prospective, randomized, phase II trial. Oncology. 2011;81(5-6):298-305. doi: 10.1159/000334456. Epub 2011 Dec 8.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 22, 2011)
90
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date November 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 82 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Israel
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00376740
Other Study ID Numbers  ICMJE sor440006ctil
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party David B. Geffen, Soroka University Medical Center
Study Sponsor  ICMJE Soroka University Medical Center
Collaborators  ICMJE Tel-Aviv Sourasky Medical Center
Investigators  ICMJE
Study Chair: Tamar Safra, M.D. Tel-Aviv Sourasky Medical Center
PRS Account Soroka University Medical Center
Verification Date August 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP