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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00436917
First received: February 15, 2007
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

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 Intervention
Breast Cancer
Osteoporosis
Drug: zoledronic acid
Procedure: Letrozole as adjuvant therapy

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Average Intra-patient Change in Total Lumbar Spine (L1 to L4) Bone Mineral Density (BMD) [ Time Frame: Baseline and 1 year ] [ Designated as safety issue: No ]
    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:
  • Total Lumbar Spine BMD as Measured by DXA at Baseline and at 24, 36, 48, and 60 > Months [ Time Frame: 5 yr ] [ Designated as safety issue: No ]
  • Femoral Neck BMD as Measured by DXA at Baseline and at 12, 24, 36, 48, and 60 Months [ Time Frame: 5 yr ] [ Designated as safety issue: No ]
  • Frequency and Severity of Toxicity as Assessed by NCI CTCAE v3.0 [ Time Frame: 5 yr ] [ Designated as safety issue: No ]
  • Time to Disease Progression [ Time Frame: 5 yr ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: April 2006
Estimated Study Completion Date: December 2014
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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®

Detailed Description:

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00436917

Locations
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
Investigators
Study Chair: Stephanie Hines, MD Mayo Clinic in Florida
Principal Investigator: Charles L. Loprinzi, MD Mayo Clinic
  More Information

Additional Information:
Publications:
Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT00436917     History of Changes
Other Study ID Numbers: MC05C8, P30CA015083, MC05C8, 2330-05
Study First Received: February 15, 2007
Results First Received: July 19, 2011
Last Updated: July 14, 2014
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Breast Neoplasms
Bone Diseases, Metabolic
Osteoporosis
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Bone Diseases
Musculoskeletal Diseases
Letrozole
Aromatase Inhibitors
Zoledronic acid
Diphosphonates
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Bone Density Conservation Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 29, 2014