Zoledronate in Preventing Bone Loss in Postmenopausal Women Who Are Receiving Letrozole for Stage I, Stage II, or Stage IIIA Breast Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2006 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00107263
First received: April 5, 2005
Last updated: June 16, 2010
Last verified: March 2006
  Purpose

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. Zoledronate may prevent bone loss in patients who are receiving letrozole. It is not yet known which schedule of zoledronate is more effective in preventing bone loss in patients with breast cancer.

PURPOSE: This randomized phase III trial is studying two different schedules of zoledronate to compare how well they work in preventing bone loss in postmenopausal women who are receiving letrozole for stage I, stage II, or stage IIIA breast cancer.


Condition Intervention Phase
Breast Cancer
Osteoporosis
Drug: letrozole
Drug: zoledronic acid
Procedure: adjuvant therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: A Randomized, Controlled, Open-Label Trial of Empiric Prophylactic vs. Delayed Use of Zoledronic Acid for Prevention of Bone Loss in Postmenopausal Women With Breast Cancer Initiating Therapy With Letrozole After Tamoxifen

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Average intra-patient change in total lumbar spine (L1-L4) bone mineral density (BMD) as measured by dual energy x-ray absorptiometry at baseline and 1 year after completion of study treatment

Secondary Outcome Measures:
  • BMD (lumbar spine) annually for 5 years after completion of study treatment
  • Incidence of osteoporosis
  • Loss of bone density
  • Hip (femoral neck) BMD
  • Incidence of bone fractures
  • Toxicity
  • Time to disease progression
  • N-telopeptide and bone-specific alkaline phosphatase at 3, 6, and 12 months

Study Start Date: January 2005
Detailed Description:

OBJECTIVES:

  • Compare the effectiveness of zoledronate vs standard care in reducing bone loss during the first 12 months of study treatment in postmenopausal women with stage I-IIIA breast cancer initiating letrozole after prior treatment with tamoxifen.
  • Compare the effect of immediate vs delayed zoledronate, annually at 2-5 years post-baseline, in reducing bone loss in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to duration of prior tamoxifen therapy (≤ 2 years vs > 2 years); time since tamoxifen therapy was discontinued (< 1 vs ≥ 1 year); prior adjuvant chemotherapy (yes vs no); and baseline total lumbar spine or femoral neck bone mineral density (BMD) T-score (> -1 standard deviation [SD] vs between -1 to -2 SD). Patients are randomized to 1 of 2 treatment arms.

  • Arm I (immediate therapy): Patients receive oral letrozole once daily. Patients also receive zoledronate IV over 15 minutes once every 6 months.
  • Arm II (delayed therapy): Patients receive oral letrozole as in arm I. Patients with radiologic evidence of bone loss after 1 year of letrozole therapy receive zoledronate as in arm I.

In both arms, treatment continues for up to 5 years in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 550 patients (275 per treatment arm) will be accrued for this study within 28 months.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Diagnosis of breast cancer

    • Stage I, II, or IIIA disease
  • Completed ≤ 6 years of adjuvant tamoxifen therapy
  • Total baseline lumbar spine or femoral neck bone mineral density T-score below -2.0 standard deviation (e.g., a patient with a T-score of -2.1 in ineligible; a patient with a T-score of -1.9 is eligible)
  • No clinical or radiological evidence of recurrent or metastatic disease
  • Hormone receptor status:

    • Estrogen receptor- and/or progesterone receptor-positive

PATIENT CHARACTERISTICS:

Age

  • Postmenopausal

Sex

  • Female

Menopausal status

  • Postmenopausal, defined by 1 of the following:

    • Over 55 years of age with cessation of menses
    • 55 years of age and under with spontaneous cessation of menses for > 1 year
    • 55 years of age and under with spontaneous cessation of menses for ≤ 1 year, but amenorrheic (e.g., spontaneous or secondary to hysterectomy) with postmenopausal estradiol levels (< 5 ng/dL)
    • Undergone bilateral oophorectomy

Performance status

  • ECOG 0-2

Life expectancy

  • At least 5 years

Hematopoietic

  • WBC ≥ 3,000/mm^3
  • Platelet count ≥ 100,000/mm^3

Hepatic

  • Alkaline phosphatase ≤ 3 times upper limit of normal (ULN)
  • AST ≤ 3 times ULN

Renal

  • Creatinine < 2.0 mg/dL
  • No hypercalcemia (i.e., calcium > 1 mg/dL above ULN within the past 6 months)
  • No hypocalcemia (i.e., calcium > 0.5 mg/dL below lower limit of normal within the past 6 months)

Other

  • No uncontrolled infection
  • No uncontrolled diabetes mellitus
  • No uncontrolled thyroid dysfunction
  • No disease affecting bone metabolism (e.g., hyperparathyroidism, hypercortisolism, Paget's disease, or osteogenesis imperfecta)
  • No malabsorption syndrome
  • No uncontrolled seizure disorder associated with falls
  • No known hypersensitivity to zoledronate or other bisphosphonates, letrozole, calcium, or cholecalciferol (vitamin D)
  • No mental illness that would preclude giving informed consent
  • 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 non-malignant systemic disease
  • No clinical or radiologic evidence of existing fracture in the lumbar spine and/or total hip
  • No history of fracture with low intensity or not associated with trauma
  • No contraindication to spinal dual energy x-ray absorptiometry (DEXA) due to any of the following:

    • History of surgery at the lumbosacral spine, with or without implantable devices
    • Scoliosis with a Cobb angle > 15° at the lumbar spine
    • Immobility, hyperostosis, or sclerotic changes at the lumbar spine
    • Evidence of sufficient sclerotic abdominal aorta that would interfere with DEXA scan
    • Any disease of the spine that would preclude proper acquisition of a lumbar spine DEXA
  • Considered reliable

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No concurrent chemotherapy

Endocrine therapy

  • See Disease Characteristics
  • Prior parathyroid hormone allowed provided it was not administered for > 1 week
  • More than 6 months since prior anabolic steroids or growth hormone
  • More than 12 months since prior endocrine therapy (including estrogen) except for the following:

    • Tamoxifen
    • Insulin
    • Oral hypoglycemics
    • Thyroid hormone
    • Steroid inhalers
  • More than 12 months since prior systemic corticosteroids except short-term corticosteroids to prevent or treat chemotherapy-induced nausea and vomiting or acute respiratory illness

    • Concurrent short-term corticosteroids allowed
  • No other concurrent hormonal therapy
  • No concurrent parathyroid hormone

Radiotherapy

  • Not specified

Surgery

  • Not specified

Other

  • Prior systemic sodium fluoride allowed provided it was not administered for > 3 months within the past 2 years
  • More than 3 weeks since prior oral bisphosphonates
  • More than 2 weeks since prior and no concurrent drugs known to affect the skeleton (e.g., calcitonin, mithramycin, or gallium nitrate)
  • More than 30 days since prior systemic investigational drugs and/or devices
  • More than 7 days since prior topical investigational drugs
  • No prior IV bisphosphonates
  • No prior aromatase inhibitor therapy
  • No concurrent calcitonin, sodium fluoride, or Tibolone
  • No other concurrent anticancer therapy
  • No other concurrent bisphosphonates
  • No other concurrent investigational drugs or devices
  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: NCT00107263

Sponsors and Collaborators
North Central Cancer Treatment Group
Investigators
Study Chair: Stephanie Hines, MD Mayo Clinic
Investigator: Edith A. Perez, MD Mayo Clinic
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00107263     History of Changes
Other Study ID Numbers: CDR0000413877, NCCTG-N03CC
Study First Received: April 5, 2005
Last Updated: June 16, 2010
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
osteoporosis
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer

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

ClinicalTrials.gov processed this record on August 28, 2014