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

NCT00107263 | Completed Phase 3

• 2 other identifiers: NCCTG-N03CCCDR0000413877
• Study Type: interventional
• Target: 558
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Breast Cancer; Osteoporosis

Keywords

osteoporosis; stage I breast cancer; stage II breast cancer; stage IIIA breast cancer

Outcome Measures

Primary Outcomes (1)

• 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

  at 12 months

Secondary Outcomes (5)

• BMD (lumbar spine) annually for 5 years after completion of study treatment

  Up to 5 years

• Incidence of osteoporosis

  Up to 5 years

• Loss of bone density

  Up to 5 years

• Incidence of bone fractures

  Up to 5 years

• Time to disease progression

  Up to 5 years

Study Arms (2)

Arm I: letrozole + zoledronate

EXPERIMENTAL

Patients receive oral letrozole once daily. Patients also receive zoledronate IV over 15 minutes once every 6 months. Treatment continues for up to 5 years in the absence of disease progression or unacceptable toxicity.

Drug: letrozole; Drug: zoledronic acid

Arm II: letrozole + zoledronate

EXPERIMENTAL

Patients receive oral letrozole once daily. Patients with radiologic evidence of bone loss after 1 year of letrozole therapy receive zoledronate as in arm I. Treatment continues for up to 5 years in the absence of disease progression or unacceptable toxicity.

Drug: letrozole; Drug: zoledronic acid

Interventions

letrozole DRUG

Arm I: letrozole + zoledronate; Arm II: letrozole + zoledronate

zoledronic acid DRUG

Arm I: letrozole + zoledronate; Arm II: letrozole + zoledronate

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator

Related Publications (2)

• Hines SL, Mincey B, Dentchev T, Sloan JA, Perez EA, Johnson DB, Schaefer PL, Alberts S, Liu H, Kahanic S, Mazurczak MA, Nikcevich DA, Loprinzi CL. Immediate versus delayed zoledronic acid for prevention of bone loss in postmenopausal women with breast cancer starting letrozole after tamoxifen-N03CC. Breast Cancer Res Treat. 2009 Oct;117(3):603-9. doi: 10.1007/s10549-009-0332-2. Epub 2009 Feb 12.

  PMID: 19214743 RESULT

• Adams A, Jakob T, Huth A, Monsef I, Ernst M, Kopp M, Caro-Valenzuela J, Wockel A, Skoetz N. Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD013451. doi: 10.1002/14651858.CD013451.pub2.

  PMID: 38979716 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Osteoporosis

Interventions

Letrozole; Zoledronic Acid

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Imidazoles

Study Officials

• Stephanie Hines, MD

  Mayo Clinic

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2005
• First Posted: April 6, 2005
• Study Start: January 1, 2005
• Primary Completion: March 1, 2007
• Study Completion: August 1, 2012
• Last Updated: December 6, 2016

Record last verified: 2016-12