Zoledronate in Treating Osteopenia or Osteoporosis in Postmenopausal Women Receiving Letrozole for Stage I, Stage II, or Stage IIIA Primary Breast Cancer

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. Identifier: NCT00436917
Recruitment Status : Completed
First Posted : February 19, 2007
Results First Posted : August 12, 2011
Last Update Posted : April 18, 2017
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Brief Summary:

RATIONALE: Zoledronate may reduce bone loss in patients receiving letrozole for breast cancer.

PURPOSE: This clinical trial is studying how well zoledronate works in treating osteopenia or osteoporosis in postmenopausal women receiving letrozole for stage I, stage II, or stage IIIA primary breast cancer.

Condition or disease Intervention/treatment Phase
Breast Cancer Osteoporosis Drug: zoledronic acid Procedure: Letrozole as adjuvant therapy Not Applicable

Detailed Description:



  • Assess changes in total lumbar spine bone mineral density (BMD) from baseline to 12 months in postmenopausal women treated with zoledronate for osteopenia or osteoporosis and letrozole for hormone receptor-positive, stage I-IIIA primary breast cancer.


  • Determine changes in total lumbar spine BMD from baseline to 2, 3, 4, and 5 years in these patients.
  • Determine changes in femoral neck BMD from baseline to 1, 2, 3, 4, and 5 years in these patients.
  • Determine time to disease progression in these patients.

OUTLINE: This is an open-label, multicenter study.

  • Adjuvant aromatase inhibitor therapy: Patients receive oral letrozole daily for up to 5 years in the absence of disease progression or unacceptable toxicity.
  • Osteoporosis management: Patients receive zoledronate IV over 15 minutes on day 1. Patients also receive oral elemental calcium twice daily and oral vitamin D daily for 6 months. Treatment repeats every 6 months for up to 5 years in the absence of disease progression or unacceptable toxicity.

Patients undergo total lumbar spine and hip (femoral neck) bone density testing by dual energy x-ray absorptiometry (DXA) at baseline and annually for 5 years.

After completion of study therapy, patients are followed at 4 weeks.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Zoledronic Acid for Treatment of Osteopenia and Osteoporosis in Women With Primary Breast Cancer Undergoing Adjuvant Aromatase Inhibitor (Letrozole) Therapy
Actual Study Start Date : April 2006
Actual Primary Completion Date : June 2008
Actual Study Completion Date : May 9, 2016

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: zoledronic acid
4 mg 15 minutes IV infusion. If creatinine clearance is ≤ 60, dosage should be adjusted as follows:CrCl 50-60: 3.5 mg; CrCl 40-49: 3.3 mg; CrCl 30-39: 3.0 mg.
Drug: zoledronic acid
zoledronic acid
Other Name: Zometa®
Procedure: Letrozole as adjuvant therapy
standard care
Other Name: Femara®

Primary Outcome Measures :
  1. Average Intra-patient Change in Total Lumbar Spine (L1 to L4) Bone Mineral Density (BMD) [ Time Frame: Baseline and 1 year ]
    Change: BMD values at twelve months post study entry minus BMD values at baseline, expressed as a percentage of the baseline value.

Secondary Outcome Measures :
  1. Total Lumbar Spine BMD as Measured by DXA at Baseline and at 24, 36, 48, and 60 > Months [ Time Frame: 5 yr ]
  2. Femoral Neck BMD as Measured by DXA at Baseline and at 12, 24, 36, 48, and 60 Months [ Time Frame: 5 yr ]
  3. Frequency and Severity of Toxicity as Assessed by NCI CTCAE v3.0 [ Time Frame: 5 yr ]
  4. Time to Disease Progression [ Time Frame: 5 yr ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No


  • Diagnosis of localized breast cancer

    • Stage I-IIIA disease
    • Adequately treated breast cancer

      • No clinical or radiological evidence of recurrent or metastatic disease
  • Baseline total lumbar spine or femoral neck bone mineral density T-score < -2.0 standard deviation (e.g., a patient with a T score of -2.1 is eligible)
  • Hormone-receptor status:

    • Estrogen receptor and/or progesterone receptor-positive breast cancer


  • Female
  • Postmenopausal, defined by 1 of the following criteria:

    • Age > 55 years with cessation of menses
    • Age ≤ 55 years with spontaneous cessation of menses for > 1 year
    • Age ≤ 55 years with spontaneous cessation of menses for ≤ 1 year, but amenorrheic (e.g., spontaneous or secondary to hysterectomy), AND has postmenopausal estradiol levels
    • Bilateral oophorectomy
  • ECOG performance status 0-2
  • Life expectancy ≥ 5 years
  • WBC ≥ 3,000/mm³ OR granulocyte count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Alkaline phosphatase ≤ 3 times upper limit of normal (ULN)
  • AST ≤ 3 times ULN
  • Creatinine < 2.0 mg/dL
  • Creatinine clearance ≥ 45 mL/min
  • No hypercalcemia (i.e., calcium level > 1 mg/dL above ULN) OR hypocalcemia (i.e., calcium level > 0.5 mg/dL below lower limit of normal) within the past 6 months
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
  • No other nonmalignant systemic diseases, including any of the following:

    • Uncontrolled infection
    • Uncontrolled diabetes mellitus
    • Uncontrolled thyroid dysfunction
    • Disease affecting bone metabolism (hyperparathyroidism, hypercortisolism, Paget's disease, osteogenesis imperfecta)
    • Malabsorption syndrome
  • No uncontrolled seizure disorders associated with falls
  • No known hypersensitivity to zoledronate or other bisphosphonates, letrozole, calcium, or vitamin D
  • No concurrent active dental problems, including any of the following:

    • Infection of the teeth or jawbone (maxillary or mandibular)
    • Dental or fixture trauma
    • Prior or current diagnosis of osteonecrosis of the jaw
    • Exposed bone in the mouth
    • Slow healing after dental procedures
  • No contraindication to spine dual energy x-ray absorptiometry (DXA) as defined by any of the following:

    • History of surgery at the lumbosacral spine, with or without implantable devices
    • Scoliosis with a Cobb angle > 15 degrees at the lumbar spine
    • Immobility, hyperostosis, or sclerotic changes at the lumbar spine, or evidence of sclerotic abdominal aorta sufficient to interfere with DXA scan
    • Disease of the spine that would preclude the proper acquisition of a lumbar spine DXA
  • No condition that would preclude study follow-up or compliance
  • No psychiatric illness that would preclude giving informed consent


  • More than 3 weeks since prior and no other concurrent oral bisphosphonates
  • No prior intravenous bisphosphonates
  • No prior aromatase inhibitor therapy
  • More than 6 months since prior anabolic steroids or growth hormone
  • More than 2 weeks since prior and no concurrent inhibitor of osteoclastic bone resorption (e.g., calcitonin, mithramycin, or gallium nitrate)
  • More than 30 days since prior systemic investigational drug and/or device
  • More than 7 days since prior topical investigational drug
  • More than 6 weeks since prior and no concurrent dental or jaw surgery (e.g., extraction, implants)
  • Concurrent short-term corticosteroid therapy allowed
  • No concurrent sodium fluoride, parathyroid hormone, or tibolone
  • No other concurrent investigational drug or device

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00436917

United States, Florida
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Study Chair: Stephanie Hines, MD Mayo Clinic
Principal Investigator: Charles L. Loprinzi, MD Mayo Clinic

Publications of Results:
Responsible Party: Mayo Clinic Identifier: NCT00436917     History of Changes
Other Study ID Numbers: MC05C8
P30CA015083 ( U.S. NIH Grant/Contract )
MC05C8 ( Other Identifier: Mayo Clinic Cancer Center )
2330-05 ( Other Identifier: Mayo Clinic IRB )
First Posted: February 19, 2007    Key Record Dates
Results First Posted: August 12, 2011
Last Update Posted: April 18, 2017
Last Verified: April 2016

Keywords provided by Mayo Clinic:
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Bone Diseases, Metabolic
Neoplasms by Site
Breast Diseases
Skin Diseases
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases
Zoledronic acid
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Bone Density Conservation Agents