OsteoporosisPhase 3NCT00332709
Safety/Efficacy of Letrozole Monotherapy or in Combination With Zoledronic Acid as Extended Adjuvant Treatment of Postmenopausal Patients With Primary Breast Cancer
A Phase 3 study testing Letrozole and Zoledronic acid in people with Osteoporosis and Postmenopausal, run by Novartis at 23 sites in Germany.
Trial summary
This was a prospective, randomized, open-label, two arm phase III trial designed to evaluate the efficacy and safety of zoledronic acid in preventing bone loss in postmenopausal women with operable breast cancer who had received 4 to 6 years of adjuvant tamoxifen therapy after resection of the tumor. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Osteoporosis, Postmenopausal
- 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
- 83 participants
- Where
- 23 sitesGermany
- Study dates
- Jan 2006to Aug 2010
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Compliant postmenopausal women with primary operable breast cancer after 4 to 6 years of therapy with tamoxifen (end of tamoxifen therapy within last 6 months)
- Performance status 0-2 (Eastern Cooperative Oncology Group)
- Patients without severe osteoporosis at study entry
- No evidence of relapse at the time of randomization
- Adequate function of bone marrow, kidney, and liver
Who cannot join
- Estrogen- and progesterone-receptor status negative or unknown
- Completion of adjuvant tamoxifen therapy more than 6 months prior to study start
- Inflammatory breast cancer
- Current/active dental problems including infection of the teeth or jawbone, dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw, of exposed bone in the mouth, or of slow healing after dental procedures.
- Recent (within 6 weeks) or planned dental or jaw surgery
- History of diseases with influence on bone metabolism such as Paget's disease and primary overactive parathyroid
Show all 10Show fewer
- Prior or concomitant therapies: chemotherapy within the last 12 months, intravenous or oral bisphosphonates, systemic corticosteroids, anabolic steroids or growth hormones, Tibolone, parathyroid hormone, systemic sodium fluoride or any drugs known to affect the skeleton (such as calcitonin, mithramycin, or gallium nitrate)
- Patients with previous or concomitant cancers (not breast cancer) within the past 5 years EXCEPT adequately treated basal or squamous cell skin cancers or in situ cancer of the cervix. Patients with previous other cancer(s) must have been disease-free for at least 5 years.
- Patients currently receiving oral bisphosphonates must discontinue these at least 3 weeks prior to study start.
- Additional protocol defined inclusion/exclusion criteria may apply.
Trial locations and contacts
23 sites in 1 country.
23 sites in 1 country
Germany23 sites
Novartis Investigative Site
Cologne
Novartis Investigative Site
Deggendorf
Novartis Investigative Site
Frankfurt am Main
Novartis Investigative Site
Freiburg im Breisgau
Novartis Investigative Site
Georgsmarienhütte
Novartis Investigative Site
Göttingen
Novartis Investigative Site
Halle
Novaertis Investigative Site
Hamein
Novartis Investigative Site
Hanover
Novartis Investigative Site
Höxter
Novartis Investigative Site
Ilsede
Novartis Investigative Site
Jena
Novartis Investigative Site
Karlsruhe
Novartis Investigative Site
Leer
Novartis Investigative Site
Lübeck
Novartis Investigative Site
Mannheim
Novartis Investigative Site
Münster
Novartis Investigative Site
Rostock
Novartis Investigative Site
Salzgitter
Novartis Investigative Site
Schwenningen
Novartis Investigative Site
Stendal
Novartis Investigative Site
Völklingen
Novartis Investigative Site
Witten
About this study
Official title: An Open Phase III Trial With Letrozole Alone or in Combination With Zoledronic Acid as Extended Adjuvant Treatment of Postmenopausal Patients With Primary Breast Cancer
This was a prospective, randomized, open-label, two arm phase III trial designed to evaluate the efficacy and safety of zoledronic acid in preventing bone loss in postmenopausal women with operable breast cancer who had received 4 to 6 years of adjuvant tamoxifen therapy after resection of the tumor. Patients were treated with letrozole 2.5 mg orally per day or letrozole 2.5 mg orally per day in combination with zoledronic acid 4 mg/6 months as an infusion.
This trial did not recruit patients in the United States.
- Conditions
- Osteoporosis, Postmenopausal
- Being tested
- Letrozole, Zoledronic acid
- Keywords
- Breast cancer, postmenopausal, bone mineral density, Zoledronic acid, Letrozole, extended adjuvant treatment., Postmenopausal women with primary hormone receptor positive breast cancer
- Medical subject headings
- Osteoporosis, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LetrozoleDrug
2.5 mg/day for 3 years
Zoledronic acidDrug
4 mg every 6 months
| Study group | Role | What they receive |
|---|---|---|
| Letrozole | Experimental | Letrozole orally 2.5 mg/day for 3 years Receives: Drug: Letrozole |
| Letrozole + Zoledronic Acid | Experimental | Letrozole orally 2.5mg/day for 3 years; Zoledronic acid 4mg every 6 months by infusion Receives: Drug: Letrozole; Drug: Zoledronic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Bone Mineral Density (BMD) From Baseline to Month 36
Change in bone mineral density (BMD) measured by dual X-ray absorptiometry (DXA) in lumbar spine (L1-L4). Change calculated by (Month 36 BMD-Baseline BMD)/Baseline BMD*100.
Measured: at 36 months as compared to baseline
Percent Change in Bone Mineral Density (BMD) From Baseline to Month 36
Bone Mineral Density is measured by dual energy x-ray absorptiometry (DXA) scan.
ANCOVA model was used in the analysis where: Variable = Baseline, Center, Treatment BMD = (Month 36 BMD-Baseline BMD)/Baseline BMD*100.
Measured: Baseline, Month 36
Change in T-score From Baseline to Month 36
BMD measured by DXA (dual energy x-ray absorptiometry) at lumbar spine, L1-L4. The T-Score is a comparison of a patient's BMD to that of a healthy 30 year of the same sex and ethnicity. The criteria of the World Health Organization are Normal is a T-Score of 1.0 or higher. Osteopenia is defined as between - 1.0 and -2.5. Osteoporosis is defined as -2.5 or lower, meaning a bone density that is two and half standard deviations below the mean of a 30 year old man/woman.
Measured: Baseline and Month 36
Change in Z Score From Baseline to Month 36
Bone Mineral Density is measured by dual energy x-ray absorptiometry (DXA). The Z-Score is the number of standard deviations a patient's BMD differs from the average BMD of their age, sex and ethnicity. A Z-score of less than minus -1.5 raises concern of factors other than aging as contributing to osteoporosis.
Measured: Baseline, month 36
Secondary outcomes (5)
Change in Bone Mineral Density From Baseline to 12 Months
Change in bone mineral density (BMD) measured by dual X-ray absorptiometry (DXA) in lumbar spine (L1-L4). Change calculated by (Month 36 BMD-Baseline BMD)/Baseline BMD*100.
Measured: Baseline, 12 months
Number of Participants With Any Kind of Fractures, by Visit.
Number of participants with fractures of any type since the last visit
Measured: Baseline, Month 6, 12, 18, 24 , 30 and 36
Median Disease Free Survival (DFS)
Disease Free Survival is measured in days and represents the number of days participants were progression free. Progression free survival is defined as the time from randomization to the date of the first documented progression or recurrence of disease or death from any cause. Median disease free survival is the time when 50% of the patients had a recurrence.
Measured: 36 months
Change in T-Score From Baseline to Month 12
BMD measured by DXA (dual energy x-ray absorptiometry) at lumbar spine, L1-L4. The T-Score is a comparison of a patient's BMD to that of a healthy 30 year of the same sex and ethnicity. The criteria of the World Health Organization are Normal is a T-Score of 1.0 or higher. Osteopenia is defined as between - 1.0 and -2.5. Osteoporosis is defined as -2.5 or lower, meaning a bone density that is two and half standard deviations below the mean of a 30 year old man/woman.
Measured: Baseline, Month 12
Change in Z-Score From Baseline to Month 12
(DXA). The Z-Score is the number of standard deviations a patient's BMD differs from the average BMD of their age, sex and ethnicity. A Z-score of less than minus -1.5 raises concern of factors other than aging as contributing to osteoporosis
Measured: Baseline, Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2006 (estimated)
- Study startJan 2006
- Primary completionAug 2010
- Study completionAug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for OsteoporosisStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 83 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00332709
- Sponsor's protocol ID
- CFEM345DDE09
- Status last verified
- Oct 2011
- First submitted
- 31 May 2006
- Last updated
- 16 Nov 2011
- Results posted
- Yes, on ClinicalTrials.gov
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 38979716
Study at a glance
From the registry record, last updated by the sponsor on 16 Nov 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Phase III Trial With Letrozole Alone or in Combination With Zoledronic Acid as Extended Adjuvant Treatment of Postmenopausal Patients With Primary Breast Cancer
- ClinicalTrials.gov ID
- NCT00332709
- Acronym / sponsor ID
- CFEM345DDE09
- Conditions
- Osteoporosis, Postmenopausal
- Keywords
- Breast cancer, postmenopausal, bone mineral density, Zoledronic acid, Letrozole, extended adjuvant treatment., Postmenopausal women with primary hormone receptor positive breast cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 83 participants (actual)
- Lead sponsor
- NovartisIndustry (pharma, biotech, devices)
- Study start
- Jan 2006
- Primary completion
- Aug 2010 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 2 Jun 2006 (estimated)
- Results
- Posted 16 Nov 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a prospective, randomized, open-label, two arm phase III trial designed to evaluate the efficacy and safety of zoledronic acid in preventing bone loss in postmenopausal women with operable breast cancer who had received 4 to 6 years of adjuvant tamoxifen therapy after resection of the tumor. Patients were treated with letrozole 2.5 mg orally per day or letrozole 2.5 mg orally per day in combination with zoledronic acid 4 mg/6 months as an infusion.
This trial did not recruit patients in the United States.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Letrozole | Experimental | Drug: LetrozoleLetrozole orally 2.5 mg/day for 3 years |
| Letrozole + Zoledronic Acid | Experimental | Drug: Letrozole, Drug: Zoledronic acidLetrozole orally 2.5mg/day for 3 years; Zoledronic acid 4mg every 6 months by infusion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Compliant postmenopausal women with primary operable breast cancer after 4 to 6 years of therapy with tamoxifen (end of tamoxifen therapy within last 6 months)
- Performance status 0-2 (Eastern Cooperative Oncology Group)
- Patients without severe osteoporosis at study entry
- No evidence of relapse at the time of randomization
- Adequate function of bone marrow, kidney, and liver
Key exclusion criteria (10 listed)
- Estrogen- and progesterone-receptor status negative or unknown
- Completion of adjuvant tamoxifen therapy more than 6 months prior to study start
- Inflammatory breast cancer
- Current/active dental problems including infection of the teeth or jawbone, dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw, of exposed bone in the mouth, or of slow healing after dental procedures.
- Recent (within 6 weeks) or planned dental or jaw surgery
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 |
|---|---|---|
| Letrozole2.5 mg/day for 3 years | Drug | Letrozole, Letrozole + Zoledronic Acid |
| Zoledronic acid4 mg every 6 months | Drug | Letrozole + Zoledronic Acid |
Primary outcome
Change in Bone Mineral Density (BMD) From Baseline to Month 36
Time frame: at 36 months as compared to baseline
Change in bone mineral density (BMD) measured by dual X-ray absorptiometry (DXA) in lumbar spine (L1-L4). Change calculated by (Month 36 BMD-Baseline BMD)/Baseline BMD*100.
Percent Change in Bone Mineral Density (BMD) From Baseline to Month 36
Time frame: Baseline, Month 36
Bone Mineral Density is measured by dual energy x-ray absorptiometry (DXA) scan. ANCOVA model was used in the analysis where: Variable = Baseline, Center, Treatment BMD = (Month 36 BMD-Baseline BMD)/Baseline BMD*100.
Change in T-score From Baseline to Month 36
Time frame: Baseline and Month 36
BMD measured by DXA (dual energy x-ray absorptiometry) at lumbar spine, L1-L4. The T-Score is a comparison of a patient's BMD to that of a healthy 30 year of the same sex and ethnicity. The criteria of the World Health Organization are Normal is a T-Score of 1.0 or higher. Osteopenia is defined as between - 1.0 and -2.5. Osteoporosis is defined as -2.5 or lower, meaning a bone density that is two and half standard deviations below the mean of a 30 year old man/woman.
Change in Z Score From Baseline to Month 36
Time frame: Baseline, month 36
Bone Mineral Density is measured by dual energy x-ray absorptiometry (DXA). The Z-Score is the number of standard deviations a patient's BMD differs from the average BMD of their age, sex and ethnicity. A Z-score of less than minus -1.5 raises concern of factors other than aging as contributing to osteoporosis.
5 secondary outcomes
Change in Bone Mineral Density From Baseline to 12 Months
Time frame: Baseline, 12 months
Number of Participants With Any Kind of Fractures, by Visit.
Time frame: Baseline, Month 6, 12, 18, 24 , 30 and 36
Median Disease Free Survival (DFS)
Time frame: 36 months
Change in T-Score From Baseline to Month 12
Time frame: Baseline, Month 12
Change in Z-Score From Baseline to Month 12
Time frame: Baseline, Month 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
23 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 Letrozole and Zoledronic acid in people with Osteoporosis and Postmenopausal, run by Novartis at 23 sites in Germany.
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 5 inclusion and 10 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 16 Nov 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in Germany. 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?
Yes. Results are posted in the registry (first posted 16 Nov 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Bone Mineral Density (BMD) From Baseline to Month 36 (time frame: at 36 months as compared to baseline). 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 NCT00332709, which also lists 1 linked publication.
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 16 Nov 2011.