Breast CancerPhase 3NCT00376740
Effectiveness of Zoledronic Acid in the Prevention of Osteoporosis in Early Breast Cancer Patients Receiving Letrozole
A Phase 3 study testing zoledronic acid in people with Breast Cancer, run by Soroka University Medical Center at 2 sites in Israel.
Trial summary
The purpose of this study is to determine whether zoledronic acid given intravenously every 6 months can prevent reduction in bone mineral density in women with early stage breast cancer receiving adjuvant therapy with the aromatase inhibitor drug letrozole, after having received adjuvant tamoxifen. Read more about this study
- Who is it for?
- Ages 18 to 82 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- zoledronic acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 2 sitesIsrael
- Study dates
- Sep 2005to Nov 2010
- 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 to 82 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Postmenopausal women with histologically documented early (non-metastatic) breast cancer
- Previous treatment with tamoxifen for at least 2.5 years and not more than 3.5 years
- Assigned to receive letrozole treatment
- Karnofsky performance status ≥ 70
- Life expectancy ≥ 16 weeks
- Signed informed consent after full explanation of study by participating clinician and prio to any study specific procedures
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- Adjuvant or neoadjuvant chemotherapy is allowed
- No clinical and/or radiologic evidence of distant metastases
- No prior treatment with an aromatase inhibitor
- Able to comply with treatment and scheduled follow-up visits
- Age between 18 and 82 years
Who cannot join
- Pregnant or lactating women or women with child bearing potential
- Patients with other malignancies except except adequately treated basal cell carcinoma of the skin or in-situ cervix carcinoma
- Active infection or other serious underlying medical condition which would impair the ability of the patient to receive protocol treatment
- Clinical and/or radiological evidence of distant metastases.
- Evidence of pathological fracture
- Prior treatment with an aromatase inhibitor
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- Prior administration of any intravenous bisphosphonate during the last year.
- Oral bisphosphonate must be discontinued within 4 weeks of enrollment
- Administration of long-term systemic corticosteroids within the last 12 months (short term steroid treatment is allowed.)
- Prior use of parathyroid hormone treatment for more than 1 week
- Use of any drug known to affect the skeleton (calcitonin, mithramycin, gallium nitrate) within two weeks prior to enrollment
- Abnormal renal function: creatinine clearance must be above 30 ml/min (calculated by Cockroft formula)
- Evidence of metabolic bone disease( Paget's, osteogenesis imperfecta, hyperparathyroidism within the 12 months prior to enrollment)
- Baseline lumbar spine and or total hip Bone Mineral Density T score below -2
- Known hypersensitivity to zoledronic acid
- Psychological, familial, sociologic, or geographic conditions which do not permit medical follow-up and compliance with the study protocol
- White blood cell ≤ 3.0 x 10exp9 /L or granulocytes ≤ 1.5 x 10exp9/L or platelets ≤100 x 10exp9
- Total bilirubin> 1.5 x upper normal limit, SGOT and SGPT > 2.5 x upper normal limit
- Unable to undergo DXA bone density scanning (spine deformity, severe scoliosis, lumbar sacral spine surgery)
Trial locations and contacts
2 sites in 1 country.
Israel2 sites
Soroka University Medical Center
Beersheba
Tel Aviv Sourasky Medical Center
Tel Aviv
About this study
Official title: Phase 3 Study of the Effect of Zoledronic Acid in the Prevention of Osteoporosis in Early Breast Cancer Patients Receiving the Aromatase Inhibitor, Letrozole, in the Adjuvant Setting
The purpose of this study is to determine whether zoledronic acid given intravenously every 6 months can prevent reduction in bone mineral density in women with early stage breast cancer receiving adjuvant therapy with the aromatase inhibitor drug letrozole, after having received adjuvant tamoxifen.
Read the detailed description
Letrozole is an aromatase inhibitor used in the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women.It has more recently been approved for use in many countries as adjuvant therapy for early breast cancer; and is often used in an adjuvant regimen following 2-3 years of tamoxifen treatment or as an extended adjuvant therapy after up to 5 years of tamoxifen. Letrozole inhibits the conversion of androgens to estrogens in vitro and in vivo. Plasma levels of estradiol and related estrogen compounds in postmenopausal patients receiving letrozole are suppressed up to 95% from baseline and are often undetectable.The estrogen deprivation in women receiving letrozole may cause increased bone resorption and bone loss.Studies comparing tamoxifen and aromatase inhibitors, in adjuvant therapy have shown an increase fracture rate, and decreased bone mineral density in patients receiving aromatase inhibitors. Zoledronic acid is an intravenously administered bisphosphonate that inhibits osteoclastic bone resorption. Intravenous bisphosphonates are effective in reducing the rate of skeletal complications, including fractures, in patients with metastatic breast cancer and other tumors when given every few weeks. Small clinical trials have given some evidence that osteoporosis can be effectively treated by one or two doses of intravenous zoledronic acid per year. This study will determine the effect of giving zoledronic acid every 6 months on the bone mineral density of patients receiving letrozole as adjuvant therapy for early breast cancer after having received adjuvant tamoxifen for at least 2.5 years. Patients will be randomized to receive zoledronic acid either at the start of letrozole therapy or when bone mineral density T score drops below - 2 standard deviation or at the occurrence of a non-trauma related fracture.
- Conditions
- Breast Cancer
- Being tested
- zoledronic acid
- Keywords
- breast cancer, postmenopausal, letrozole, zoledronic acid, adjuvant,bone mineral density
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
zoledronic acidDrug
Also called Zomera, zolendronate
Zoledronic acid 4 mg IV every 6 months up to 2.5 years after the start of letrozole treatment.
| Study group | Role | What they receive |
|---|---|---|
| Immediate zoledronic acid | Experimental | Patients on this arm will receive zoledronic acid every 6 months during 2.5 years of letrozole therapy starting within 3 months of the start of letrozole therapy. (5 doses of zoledronic acid) Receives: Drug: zoledronic acid |
| Delayed zoledronic acid | Active comparator | Patients on this arm will receive zoledronic acid during the 2.5 years of letrozole treatment only after the T-score on bone mineral density testing falls below minus 2.0. Receives: Drug: zoledronic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
bone mineral density
bone events
renal function
liver function
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2006 (estimated)
- Study startSep 2005
- Primary completionNov 2010
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.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Soroka University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Tel-Aviv Sourasky Medical Center
- Responsible party
- Principal investigator, David B. Geffen, Soroka University Medical Center
- Investigators
- Tamar Safra, M.D., Study chair, Tel-Aviv Sourasky Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00376740
- Sponsor's protocol ID
- sor440006ctil
- Status last verified
- Aug 2011
- First submitted
- 14 Sep 2006
- Last updated
- 23 Aug 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 38979716Safra T, Bernstein-Molho R, Greenberg J, Pelles-Avraham S, Stephansky I, Sarid D, Inbar MJ, Stemmer SM, Geffen DB. The protective effect of zoledronic acid on bone loss in postmenopausal women with early breast cancer treated with sequential tamoxifen and letrozole: a prospective, randomized, phase II trial. Oncology. 2011;81(5-6):298-305. doi: 10.1159/000334456. Epub 2011 Dec 8.
PubMed 22156381
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 3 Study of the Effect of Zoledronic Acid in the Prevention of Osteoporosis in Early Breast Cancer Patients Receiving the Aromatase Inhibitor, Letrozole, in the Adjuvant Setting
- ClinicalTrials.gov ID
- NCT00376740
- Acronym / sponsor ID
- sor440006ctil
- Conditions
- Breast Cancer
- Keywords
- breast cancer, postmenopausal, letrozole, zoledronic acid, adjuvant,bone mineral density
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Soroka University Medical CenterUniversity, hospital or other
- Collaborators
- Tel-Aviv Sourasky Medical Center
- Study start
- Sep 2005
- Primary completion
- Nov 2010 (actual)
- First posted
- 15 Sep 2006 (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.
The purpose of this study is to determine whether zoledronic acid given intravenously every 6 months can prevent reduction in bone mineral density in women with early stage breast cancer receiving adjuvant therapy with the aromatase inhibitor drug letrozole, after having received adjuvant tamoxifen.
Detailed description
Letrozole is an aromatase inhibitor used in the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women.It has more recently been approved for use in many countries as adjuvant therapy for early breast cancer; and is often used in an adjuvant regimen following 2-3 years of tamoxifen treatment or as an extended adjuvant therapy after up to 5 years of tamoxifen. Letrozole inhibits the conversion of androgens to estrogens in vitro and in vivo. Plasma levels of estradiol and related estrogen compounds in postmenopausal patients receiving letrozole are suppressed up to 95% from baseline and are often undetectable.The estrogen deprivation in women receiving letrozole may cause increased bone resorption and bone loss.Studies comparing tamoxifen and aromatase inhibitors, in adjuvant therapy have shown an increase fracture rate, and decreased bone mineral density in patients receiving aromatase inhibitors. Zoledronic acid is an intravenously administered bisphosphonate that inhibits osteoclastic bone resorption. Intravenous bisphosphonates are effective in reducing the rate of skeletal complications, including fractures, in patients with metastatic breast cancer and other tumors when given every few weeks. Small clinical trials have given some evidence that osteoporosis can be effectively treated by one or two doses of intravenous zoledronic acid per year. This study will determine the effect of giving zoledronic acid every 6 months on the bone mineral density of patients receiving letrozole as adjuvant therapy for early breast cancer after having received adjuvant tamoxifen for at least 2.5 years. Patients will be randomized to receive zoledronic acid either at the start of letrozole therapy or when bone mineral density T score drops below - 2 standard deviation or at the occurrence of a non-trauma related fracture.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Immediate zoledronic acid | Experimental | Drug: zoledronic acidPatients on this arm will receive zoledronic acid every 6 months during 2.5 years of letrozole therapy starting within 3 months of the start of letrozole therapy. (5 doses of zoledronic acid) |
| Delayed zoledronic acid | Active comparator | Drug: zoledronic acidPatients on this arm will receive zoledronic acid during the 2.5 years of letrozole treatment only after the T-score on bone mineral density testing falls below minus 2.0. |
Who may qualify
- Ages
- 18 to 82 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Postmenopausal women with histologically documented early (non-metastatic) breast cancer
- Previous treatment with tamoxifen for at least 2.5 years and not more than 3.5 years
- Assigned to receive letrozole treatment
- Karnofsky performance status ≥ 70
- Life expectancy ≥ 16 weeks
Key exclusion criteria (19 listed)
- Pregnant or lactating women or women with child bearing potential
- Patients with other malignancies except except adequately treated basal cell carcinoma of the skin or in-situ cervix carcinoma
- Active infection or other serious underlying medical condition which would impair the ability of the patient to receive protocol treatment
- Clinical and/or radiological evidence of distant metastases.
- Evidence of pathological fracture
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 |
|---|---|---|
| zoledronic acidAlso: Zomera, zolendronateZoledronic acid 4 mg IV every 6 months up to 2.5 years after the start of letrozole treatment. | Drug | Delayed zoledronic acid, Immediate zoledronic acid |
Primary outcome
bone mineral density
bone events
renal function
liver function
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 23 Aug 2011.
- 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.
- Derived from this study: PubMed 22156381Safra T, Bernstein-Molho R, Greenberg J, Pelles-Avraham S, Stephansky I, Sarid D, Inbar MJ, Stemmer SM, Geffen DB. The protective effect of zoledronic acid on bone loss in postmenopausal women with early breast cancer treated with sequential tamoxifen and letrozole: a prospective, randomized, phase II trial. Oncology. 2011;81(5-6):298-305. doi: 10.1159/000334456. Epub 2011 Dec 8.
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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.
Tamar Safra, M.D. study chair
Tel-Aviv Sourasky Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing zoledronic acid in people with Breast Cancer, run by Soroka University Medical Center at 2 sites in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 19 exclusion criteria. 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 23 Aug 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
bone mineral density. The study lists 4 primary outcomes in all. 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 NCT00376740, 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 23 Aug 2011.