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

Mayo Clinic

Status: Completed

Conditions: Osteoporosis; Breast Cancer

Treatments: Drug: zoledronic acid; Procedure: Letrozole as adjuvant therapy

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00436917

P30CA015083 (U.S. NIH Grant/Contract)

2330-05 (Other Identifier)

MC05C8 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 patients

Sex: Female

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Supportive Care

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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60 participants in 1 patient group

zoledronic acid

Experimental group

Description:

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.

Treatment:

Procedure: Letrozole as adjuvant therapy

Drug: zoledronic acid