Breast Cancer
Conditions
Keywords
breast cancer, letrozole, zoledronic acid, adjuvant, postmenopausal
Brief summary
Post-menopausal breast cancer patients will receive letrozole 2.5 mg daily for the treatment of breast cancer and will be randomized to a treatment group to receive either upfront zoledronic acid 4 mg IV 15-minute infusion every 6 months or delayed start zoledronic acid 4 mg IV 15-minute infusion every 6 months. Delayed start zoledronic acid will be initiated when either the Bone Mineral Density T-score is below -2 Standard Deviations at either the lumbar spine or hip or any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the month 36 scheduled visit. Letrozole 2.5 mg will be given daily for 5 years.
Interventions
DRUGZoledronic acid
Zoledronic acid 4 mg Intravenous (IV)15 minute infusion every 6 months.
DRUGLetrozole
Letrozole tablets 2.5 mg/day/taken orally for 5 years.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Stage I-IIIa breast cancer * Postmenopausal * Recent surgery for breast cancer
Exclusion criteria
* Metastatic disease * Invasive bilateral disease * Clinical or radiological evidence of existing fracture in spine or hip Other protocol-defined inclusion /
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Lumbar Spine (L2-L4) BMD After 12 Months of Letrozole Therapy | From Baseline - 12 months | Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = \[(BMD at Visit - BMD at Baseline) / BMD at Baseline\] \* 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Lumbar Spine (L2-L4) BMD at 2 Years, 3 Years, 4 Years and 5 Years | From Baseline to Year 2, Year 3, Year 4, Year 5 | Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = \[(BMD at Visit - BMD at Baseline) / BMD at Baseline\] \* 100. |
| Percent Change in Lumbar Spine (L1-L4) BMD at Year 1, Year 2, Year 3, Year 4 and Year 5 | From Baseline to Year 1, Year 2, Year 3, Year 4, Year 5 | Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = \[(BMD at Visit - BMD at Baseline) / BMD at Baseline\] \* 100. |
| Percent Change in Total Hip BMD at Year 1, Year 2, Year 3, Year 4 and Year 5 | From baseline to Year 1, Year 2, Year 3, Year 4, Year 5 | Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = \[(BMD at Visit - BMD at Baseline) / BMD at Baseline\] \* 100. |
| Percentage of Participants With Radiological (Vertebra) Fractures Which Were Not Present at Baseline But Were Present at Year 3 | Year 3 | Radiological Fracture at 36 months which was not present at baseline = (new fracture/number participant analyzed)\*100. Evaluation of radiological fractures were based on central lab X-ray data. A subject with multiple fractures at the same time or multiple fractures with the same grade is counted only once for that treatment. |
Countries
Argentina, Belgium, France, Italy, Netherlands, Saudi Arabia, South Africa, South Korea, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Upfront Zoledronic Acid Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1. | 263 |
| Delayed Zoledronic Acid Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score \<= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1. | 264 |
| Total | 527 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal Test Procedure Results | 9 | 3 |
| Overall Study | Administrative Problems | 4 | 3 |
| Overall Study | Adverse Event | 44 | 41 |
| Overall Study | Death | 2 | 1 |
| Overall Study | Lack of Efficacy | 19 | 14 |
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Protocol Violation | 3 | 7 |
| Overall Study | Withdrawal by Subject | 9 | 6 |
Baseline characteristics
| Characteristic | Upfront Zoledronic Acid | Delayed Zoledronic Acid | Total |
|---|---|---|---|
| Age Continuous | 58.2 years STANDARD_DEVIATION 8.19 | 58.4 years STANDARD_DEVIATION 7.73 | 58.29 years STANDARD_DEVIATION 7.96 |
| Sex: Female, Male Female | 263 Participants | 264 Participants | 527 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 225 / 254 | 240 / 269 |
| serious Total, serious adverse events | 47 / 254 | 56 / 269 |
Outcome results
Primary
Percent Change in Lumbar Spine (L2-L4) BMD After 12 Months of Letrozole Therapy
Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = \[(BMD at Visit - BMD at Baseline) / BMD at Baseline\] \* 100.
Time frame: From Baseline - 12 months
Population: For the analysis of safety, the safety population for treatment arms were defined by the actual treatment received, rather than the treatment arm assigned by randomization. Participants with observations at baseline and 12 months were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Upfront Zoledronic Acid | Percent Change in Lumbar Spine (L2-L4) BMD After 12 Months of Letrozole Therapy | 2.680 Percent Change | Standard Deviation 2.8451 |
| Delayed Zoledronic Acid | Percent Change in Lumbar Spine (L2-L4) BMD After 12 Months of Letrozole Therapy | -3.314 Percent Change | Standard Deviation 3.9632 |
Secondary
Percentage of Participants With Radiological (Vertebra) Fractures Which Were Not Present at Baseline But Were Present at Year 3
Radiological Fracture at 36 months which was not present at baseline = (new fracture/number participant analyzed)\*100. Evaluation of radiological fractures were based on central lab X-ray data. A subject with multiple fractures at the same time or multiple fractures with the same grade is counted only once for that treatment.
Time frame: Year 3
Population: For the analysis of safety, the safety population for treatment arms were defined by the actual treatment received, rather than the treatment arm assigned by randomization. Participants with observations at Year 3 were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Upfront Zoledronic Acid | Percentage of Participants With Radiological (Vertebra) Fractures Which Were Not Present at Baseline But Were Present at Year 3 | 2.8 Percentage of Participants |
| Delayed Zoledronic Acid | Percentage of Participants With Radiological (Vertebra) Fractures Which Were Not Present at Baseline But Were Present at Year 3 | 3.3 Percentage of Participants |
Secondary
Percent Change in Lumbar Spine (L1-L4) BMD at Year 1, Year 2, Year 3, Year 4 and Year 5
Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = \[(BMD at Visit - BMD at Baseline) / BMD at Baseline\] \* 100.
Time frame: From Baseline to Year 1, Year 2, Year 3, Year 4, Year 5
Population: For the analysis of safety, the safety population for treatment arms were defined by the actual treatment received, rather than the treatment arm assigned by randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Upfront Zoledronic Acid | Percent Change in Lumbar Spine (L1-L4) BMD at Year 1, Year 2, Year 3, Year 4 and Year 5 | Year 2 (n=122, 142) | 3.994 Percent Change | Standard Deviation 3.6344 |
| Upfront Zoledronic Acid | Percent Change in Lumbar Spine (L1-L4) BMD at Year 1, Year 2, Year 3, Year 4 and Year 5 | Year 4 (n=104, 122) | 5.051 Percent Change | Standard Deviation 4.9739 |
| Upfront Zoledronic Acid | Percent Change in Lumbar Spine (L1-L4) BMD at Year 1, Year 2, Year 3, Year 4 and Year 5 | Year 3 (n=199, 133) | 4.523 Percent Change | Standard Deviation 4.5197 |
| Upfront Zoledronic Acid | Percent Change in Lumbar Spine (L1-L4) BMD at Year 1, Year 2, Year 3, Year 4 and Year 5 | Year 5 (n=86, 102) | 5.476 Percent Change | Standard Deviation 5.0395 |
| Upfront Zoledronic Acid | Percent Change in Lumbar Spine (L1-L4) BMD at Year 1, Year 2, Year 3, Year 4 and Year 5 | Year 1 (n=123, 156) | 2.330 Percent Change | Standard Deviation 2.7465 |
| Delayed Zoledronic Acid | Percent Change in Lumbar Spine (L1-L4) BMD at Year 1, Year 2, Year 3, Year 4 and Year 5 | Year 5 (n=86, 102) | -4.692 Percent Change | Standard Deviation 6.0242 |
| Delayed Zoledronic Acid | Percent Change in Lumbar Spine (L1-L4) BMD at Year 1, Year 2, Year 3, Year 4 and Year 5 | Year 1 (n=123, 156) | -3.532 Percent Change | Standard Deviation 3.783 |
| Delayed Zoledronic Acid | Percent Change in Lumbar Spine (L1-L4) BMD at Year 1, Year 2, Year 3, Year 4 and Year 5 | Year 2 (n=122, 142) | -3.934 Percent Change | Standard Deviation 4.7162 |
| Delayed Zoledronic Acid | Percent Change in Lumbar Spine (L1-L4) BMD at Year 1, Year 2, Year 3, Year 4 and Year 5 | Year 3 (n=199, 133) | -4.292 Percent Change | Standard Deviation 5.2317 |
| Delayed Zoledronic Acid | Percent Change in Lumbar Spine (L1-L4) BMD at Year 1, Year 2, Year 3, Year 4 and Year 5 | Year 4 (n=104, 122) | -4.713 Percent Change | Standard Deviation 5.4101 |
Secondary
Percent Change in Lumbar Spine (L2-L4) BMD at 2 Years, 3 Years, 4 Years and 5 Years
Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = \[(BMD at Visit - BMD at Baseline) / BMD at Baseline\] \* 100.
Time frame: From Baseline to Year 2, Year 3, Year 4, Year 5
Population: Analysis of safety:safety population for treatment arms were defined by the actual treatment received, rather than the treatment arm assigned by randomization. n in each category indicates participants with data at baseline and each corresponding timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Upfront Zoledronic Acid | Percent Change in Lumbar Spine (L2-L4) BMD at 2 Years, 3 Years, 4 Years and 5 Years | Year 2 (n=122,142) | 4.136 Percent Change | Standard Deviation 3.8182 |
| Upfront Zoledronic Acid | Percent Change in Lumbar Spine (L2-L4) BMD at 2 Years, 3 Years, 4 Years and 5 Years | Year 3 (n=119,133) | 4.777 Percent Change | Standard Deviation 4.8959 |
| Upfront Zoledronic Acid | Percent Change in Lumbar Spine (L2-L4) BMD at 2 Years, 3 Years, 4 Years and 5 Years | Year 4 (n=104, 122) | 5.462 Percent Change | Standard Deviation 5.2922 |
| Upfront Zoledronic Acid | Percent Change in Lumbar Spine (L2-L4) BMD at 2 Years, 3 Years, 4 Years and 5 Years | Year 5 (n=86, 102) | 6.013 Percent Change | Standard Deviation 5.4366 |
| Delayed Zoledronic Acid | Percent Change in Lumbar Spine (L2-L4) BMD at 2 Years, 3 Years, 4 Years and 5 Years | Year 5 (n=86, 102) | -4.572 Percent Change | Standard Deviation 6.1617 |
| Delayed Zoledronic Acid | Percent Change in Lumbar Spine (L2-L4) BMD at 2 Years, 3 Years, 4 Years and 5 Years | Year 2 (n=122,142) | -3.924 Percent Change | Standard Deviation 4.7442 |
| Delayed Zoledronic Acid | Percent Change in Lumbar Spine (L2-L4) BMD at 2 Years, 3 Years, 4 Years and 5 Years | Year 4 (n=104, 122) | -4.746 Percent Change | Standard Deviation 5.6588 |
| Delayed Zoledronic Acid | Percent Change in Lumbar Spine (L2-L4) BMD at 2 Years, 3 Years, 4 Years and 5 Years | Year 3 (n=119,133) | -4.297 Percent Change | Standard Deviation 5.3583 |
Secondary
Percent Change in Total Hip BMD at Year 1, Year 2, Year 3, Year 4 and Year 5
Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = \[(BMD at Visit - BMD at Baseline) / BMD at Baseline\] \* 100.
Time frame: From baseline to Year 1, Year 2, Year 3, Year 4, Year 5
Population: For the analysis of safety, the safety population for treatment arms were defined by the actual treatment received, rather than the treatment arm assigned by randomization. During different time points, participants with observations at that time point were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Upfront Zoledronic Acid | Percent Change in Total Hip BMD at Year 1, Year 2, Year 3, Year 4 and Year 5 | Year 2 (n=169, 168) | 2.119 Percent Change | Standard Deviation 2.9435 |
| Upfront Zoledronic Acid | Percent Change in Total Hip BMD at Year 1, Year 2, Year 3, Year 4 and Year 5 | Year 4 (n=145, 152) | 2.439 Percent Change | Standard Deviation 3.5236 |
| Upfront Zoledronic Acid | Percent Change in Total Hip BMD at Year 1, Year 2, Year 3, Year 4 and Year 5 | Year 1 (n=173, 187) | 1.637 Percent Change | Standard Deviation 2.4371 |
| Upfront Zoledronic Acid | Percent Change in Total Hip BMD at Year 1, Year 2, Year 3, Year 4 and Year 5 | Year 5 (n=119, 121) | 2.788 Percent Change | Standard Deviation 3.8386 |
| Upfront Zoledronic Acid | Percent Change in Total Hip BMD at Year 1, Year 2, Year 3, Year 4 and Year 5 | Year 3 (n=163, 162) | 1.991 Percent Change | Standard Deviation 3.4207 |
| Delayed Zoledronic Acid | Percent Change in Total Hip BMD at Year 1, Year 2, Year 3, Year 4 and Year 5 | Year 5 (n=119, 121) | -4.012 Percent Change | Standard Deviation 5.1321 |
| Delayed Zoledronic Acid | Percent Change in Total Hip BMD at Year 1, Year 2, Year 3, Year 4 and Year 5 | Year 2 (n=169, 168) | -2.628 Percent Change | Standard Deviation 3.5659 |
| Delayed Zoledronic Acid | Percent Change in Total Hip BMD at Year 1, Year 2, Year 3, Year 4 and Year 5 | Year 3 (n=163, 162) | -3.011 Percent Change | Standard Deviation 4.7684 |
| Delayed Zoledronic Acid | Percent Change in Total Hip BMD at Year 1, Year 2, Year 3, Year 4 and Year 5 | Year 4 (n=145, 152) | -3.074 Percent Change | Standard Deviation 5.4515 |
| Delayed Zoledronic Acid | Percent Change in Total Hip BMD at Year 1, Year 2, Year 3, Year 4 and Year 5 | Year 1 (n=173, 187) | -1.644 Percent Change | Standard Deviation 2.9994 |