Breast CancerPhase 3NCT00107263
Zoledronate in Preventing Bone Loss in Postmenopausal Women Who Are Receiving Letrozole for Stage I, Stage II, or Stage IIIA Breast Cancer
A Phase 3 study testing letrozole and zoledronic acid in people with Breast Cancer and Osteoporosis, run by Alliance for Clinical Trials in Oncology.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer, Osteoporosis
- What is being tested?
- letrozole and zoledronic acid
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 558 participants
- Where
- No sites listed yet
- Study dates
- Jan 2005to Aug 2012
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
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
About this study
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
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.
Read the 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.
- Conditions
- Breast Cancer, Osteoporosis
- Being tested
- letrozole, zoledronic acid
- Keywords
- osteoporosis, stage I breast cancer, stage II breast cancer, stage IIIA breast cancer
- Medical subject headings
- Breast Neoplasms, Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
letrozoleDrug
zoledronic acidDrug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: letrozole; Drug: zoledronic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: at 12 months
Secondary outcomes (5)
BMD (lumbar spine) annually for 5 years after completion of study treatment
Measured: Up to 5 years
Incidence of osteoporosis
Measured: Up to 5 years
Loss of bone density
Measured: Up to 5 years
Incidence of bone fractures
Measured: Up to 5 years
Time to disease progression
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2005 (estimated)
- Study startJan 2005
- Primary completionMar 2007
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Alliance for Clinical Trials in OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 558 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alliance for Clinical Trials in Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Stephanie Hines, MD, Study chair, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00107263
- Sponsor's protocol ID
- NCCTG-N03CC
- Other IDs
- CDR0000413877
- Status last verified
- Dec 2016
- First submitted
- 5 Apr 2005
- Last updated
- 6 Dec 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 19214743Adams 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.
PubMed 38979716
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00107263
- Acronym / sponsor ID
- NCCTG-N03CC
- Conditions
- Breast Cancer, Osteoporosis
- Keywords
- osteoporosis, stage I breast cancer, stage II breast cancer, stage IIIA breast cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 558 participants (actual)
- Lead sponsor
- Alliance for Clinical Trials in OncologyUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jan 2005
- Primary completion
- Mar 2007 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 6 Apr 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I: letrozole + zoledronate | Experimental | Drug: letrozole, Drug: zoledronic acidPatients 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. |
| Arm II: letrozole + zoledronate | Experimental | Drug: letrozole, Drug: zoledronic acidPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| letrozole | Drug | Arm I: letrozole + zoledronate, Arm II: letrozole + zoledronate |
| zoledronic acid | Drug | Arm I: letrozole + zoledronate, Arm II: letrozole + zoledronate |
Primary outcome
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
Time frame: at 12 months
5 secondary outcomes
BMD (lumbar spine) annually for 5 years after completion of study treatment
Time frame: Up to 5 years
Incidence of osteoporosis
Time frame: Up to 5 years
Loss of bone density
Time frame: Up to 5 years
Incidence of bone fractures
Time frame: Up to 5 years
Time to disease progression
Time frame: Up to 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2016.
- Results publication: PubMed 19214743Hines 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.
- Derived from this study: PubMed 38979716Adams 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.
Related trials for Breast Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephanie Hines, MD study chair
Mayo Clinic
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing letrozole and zoledronic acid in people with Breast Cancer and Osteoporosis, run by Alliance for Clinical Trials in Oncology.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: at 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00107263, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2016.