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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Letrozole | Experimental | Letrozole orally 2.5 mg/day for 3 years |
|
| Letrozole + Zoledronic Acid | Experimental | Letrozole orally 2.5mg/day for 3 years; Zoledronic acid 4mg every 6 months by infusion |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Letrozole | Drug | 2.5 mg/day for 3 years |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. | 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. | Baseline, month 36 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline, 12 months |
| Number of Participants With Any Kind of Fractures, by Visit. |
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Inclusion Criteria:
Exclusion Criteria:
Additional protocol defined inclusion/exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Cologne | Germany | ||||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38979716 | Derived | 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. |
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Total Randomized participants were 83. 2 patients were enrolled but never received study medication. Hence, 81 were included in the safety population.
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| ID | Title | Description |
|---|---|---|
| FG000 | Letrozole | Letrozole 2.5 mg/day for 3 years |
| FG001 | Letrozole + Zoledronic Acid | Letrozole 2.5mg/day for 3 years plus Zoledronic acid 4mg every 6 months |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Zoledronic acid |
| Drug |
4 mg every 6 months |
|
Number of participants with fractures of any type since the last visit |
| 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. | 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. | 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 | Baseline, Month 12 |
| Deggendorf |
| Germany |
| Novartis Investigative Site | Frankfurt am Main | Germany |
| Novartis Investigative Site | Freiburg im Breisgau | Germany |
| Novartis Investigative Site | Georgsmarienhütte | Germany |
| Novartis Investigative Site | Göttingen | Germany |
| Novartis Investigative Site | Halle | Germany |
| Novaertis Investigative Site | Hamein | Germany |
| Novartis Investigative Site | Hanover | Germany |
| Novartis Investigative Site | Höxter | Germany |
| Novartis Investigative Site | Ilsede | Germany |
| Novartis Investigative Site | Jena | Germany |
| Novartis Investigative Site | Karlsruhe | Germany |
| Novartis Investigative Site | Leer | Germany |
| Novartis Investigative Site | Lübeck | Germany |
| Novartis Investigative Site | Mannheim | Germany |
| Novartis Investigative Site | Münster | Germany |
| Novartis Investigative Site | Rostock | Germany |
| Novartis Investigative Site | Salzgitter | Germany |
| Novartis Investigative Site | Schwenningen | Germany |
| Novartis Investigative Site | Stendal | Germany |
| Novartis Investigative Site | Völklingen | Germany |
| Novartis Investigative Site | Witten | Germany |
| COMPLETED |
|
| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Letrozole | Letrozole 2.5 mg/day for 3 years |
| BG001 | Letrozole + Zoledronic Acid | Letrozole 2.5mg/day for 3 years plus Zoledronic acid 4mg every 6 months |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Demographic data is provided for the Intent to Treat population. | Count of Participants | Participants |
| |||||||||||||||||
| Age Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | (ITT) The study population will consist of post menopausal breast cancer patients who have completed 4 to 6 years of adjuvant Tamoxifen therapy after therapy. Participants with observations at both baseline and endpoint were included in the analysis. | Posted | Mean | Standard Deviation | Percent | at 36 months as compared to baseline |
|
|
| ||||||||||||||||||||||||||||
| Secondary | 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. | (ITT) The study population will consist of post menopausal breast cancer patients who have completed 4 to 6 years of adjuvant Tamoxifen therapy after therapy. Participants with observations at both baseline and endpoint were included in the analysis. | Posted | Mean | Standard Deviation | g/cm^2 | Baseline, 12 months |
|
| |||||||||||||||||||||||||||||
| Secondary | Number of Participants With Any Kind of Fractures, by Visit. | Number of participants with fractures of any type since the last visit | (ITT) The study population will consist of post menopausal breast cancer patients who have completed 4 to 6 years of adjuvant Tamoxifen therapy after therapy. Participants with observations from baseline to month 36 were included in this analysis. | Posted | Number | Participants | Baseline, Month 6, 12, 18, 24 , 30 and 36 |
|
| ||||||||||||||||||||||||||||||
| Secondary | 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. | (ITT) The study population will consist of post menopausal breast cancer patients who have completed 4 to 6 years of adjuvant Tamoxifen therapy after therapy. The median disease free survival was not observed because patients in the combination therapy did not have any recurrences. | Posted | Median | 95% Confidence Interval | Months | 36 months |
|
| |||||||||||||||||||||||||||||
| Primary | 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. | (ITT) The study population will consist of post menopausal breast cancer patients who have completed 4 to 6 years of adjuvant Tamoxifen therapy after therapy. Participants with observations at both baseline and endpoint were included in the analysis. | Posted | Mean | Standard Deviation | Percent Change in BMD | Baseline, Month 36 |
|
| |||||||||||||||||||||||||||||
| Primary | 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. | (ITT) The study population will consist of post menopausal breast cancer patients who have completed 4 to 6 years of adjuvant Tamoxifen therapy after therapy.Participants with observations at both baseline and endpoint were included in the analysis. | Posted | Mean | Standard Deviation | T-Score | Baseline and Month 36 |
|
| |||||||||||||||||||||||||||||
| Primary | 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. | (ITT) The study population will consist of post menopausal breast cancer patients who have completed 4 to 6 years of adjuvant Tamoxifen therapy after therapy. Participants with observations at both baseline and endpoint were included in the analysis. | Posted | Mean | Standard Deviation | Z-Score | Baseline, month 36 |
|
| |||||||||||||||||||||||||||||
| Secondary | 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. | (ITT) The study population will consist of post menopausal breast cancer patients who have completed 4 to 6 years of adjuvant Tamoxifen therapy after therapy. Participants with observations at both baseline and endpoint were included in this analysis. | Posted | Mean | Standard Deviation | T-Score | Baseline, Month 12 |
|
| |||||||||||||||||||||||||||||
| Secondary | 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 | (ITT) The study population will consist of post menopausal breast cancer patients who have completed 4 to 6 years of adjuvant Tamoxifen therapy after therapy. Participants with observations at both baseline and endpoint were included in this analysis | Posted | Mean | Standard Deviation | Z-Score | Baseline, Month 12 |
|
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Letrozole | Letrozole orally 2.5 mg/day for 3 years | 6 | 40 | 35 | 40 | ||
| EG001 | Letrozole + Zolendronic Acid | Letrozole 2.5mg/day for 3 years plus Zoledronic acid 4mg every 6 months | 7 | 41 | 35 | 41 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ACUTE MYOCARDIAL INFARCTION | Cardiac disorders | MedDRA 10.X | Systematic Assessment |
| |
| ANGINA PECTORIS | Cardiac disorders | MedDRA 10.X | Systematic Assessment |
| |
| ANGINA UNSTABLE | Cardiac disorders | MedDRA 10.X | Systematic Assessment |
| |
| CORONARY ARTERY STENOSIS | Cardiac disorders | MedDRA 10.X | Systematic Assessment |
| |
| SUPRAVENTRICULAR TACHYCARDIA | Cardiac disorders | MedDRA 10.X | Systematic Assessment |
| |
| VERTIGO POSITIONAL | Ear and labyrinth disorders | MedDRA 10.X | Systematic Assessment |
| |
| CONCOMITANT DISEASE PROGRESSION | General disorders | MedDRA 10.X | Systematic Assessment |
| |
| CHOLECYSTITIS | Hepatobiliary disorders | MedDRA 10.X | Systematic Assessment |
| |
| DIVERTICULITIS | Infections and infestations | MedDRA 10.X | Systematic Assessment |
| |
| CONTUSION | Injury, poisoning and procedural complications | MedDRA 10.X | Systematic Assessment |
| |
| FALL | Injury, poisoning and procedural complications | MedDRA 10.X | Systematic Assessment |
| |
| LOWER LIMB FRACTURE | Injury, poisoning and procedural complications | MedDRA 10.X | Systematic Assessment |
| |
| ROAD TRAFFIC ACCIDENT | Injury, poisoning and procedural complications | MedDRA 10.X | Systematic Assessment |
| |
| VASCULAR PSEUDOANEURYSM | Injury, poisoning and procedural complications | MedDRA 10.X | Systematic Assessment |
| |
| OXYGEN SATURATION DECREASED | Investigations | MedDRA 10.X | Systematic Assessment |
| |
| AXILLARY MASS | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
| |
| COMPARTMENT SYNDROME | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
| |
| OSTEOARTHRITIS | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
| |
| METASTASES TO BONE | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 10.X | Systematic Assessment |
| |
| METASTASES TO LIVER | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 10.X | Systematic Assessment |
| |
| METASTASES TO LUNG | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 10.X | Systematic Assessment |
| |
| VAGINAL HAEMORRHAGE | Reproductive system and breast disorders | MedDRA 10.X | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| VERTIGO | Ear and labyrinth disorders | MedDRA 10.X | Systematic Assessment |
| |
| ABDOMINAL PAIN UPPER | Gastrointestinal disorders | MedDRA 10.X | Systematic Assessment |
| |
| CONSTIPATION | Gastrointestinal disorders | MedDRA 10.X | Systematic Assessment |
| |
| DIARRHOEA | Gastrointestinal disorders | MedDRA 10.X | Systematic Assessment |
| |
| DRY MOUTH | Gastrointestinal disorders | MedDRA 10.X | Systematic Assessment |
| |
| DYSPEPSIA | Gastrointestinal disorders | MedDRA 10.X | Systematic Assessment |
| |
| NAUSEA | Gastrointestinal disorders | MedDRA 10.X | Systematic Assessment |
| |
| CHILLS | General disorders | MedDRA 10.X | Systematic Assessment |
| |
| FATIGUE | General disorders | MedDRA 10.X | Systematic Assessment |
| |
| INFLUENZA LIKE ILLNESS | General disorders | MedDRA 10.X | Systematic Assessment |
| |
| OEDEMA PERIPHERAL | General disorders | MedDRA 10.X | Systematic Assessment |
| |
| PYREXIA | General disorders | MedDRA 10.X | Systematic Assessment |
| |
| HEPATIC CYST | Hepatobiliary disorders | MedDRA 10.X | Systematic Assessment |
| |
| CYSTITIS | Infections and infestations | MedDRA 10.X | Systematic Assessment |
| |
| NASOPHARYNGITIS | Infections and infestations | MedDRA 10.X | Systematic Assessment |
| |
| DECREASED APPETITE | Metabolism and nutrition disorders | MedDRA 10.X | Systematic Assessment |
| |
| ARTHRALGIA | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
| |
| BACK PAIN | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
| |
| BONE PAIN | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
| |
| MUSCLE SPASMS | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
| |
| MUSCULOSKELETAL PAIN | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
| |
| MYALGIA | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
| |
| NECK PAIN | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
| |
| OSTEOARTHRITIS | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
| |
| OSTEOPENIA | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
| |
| PAIN IN EXTREMITY | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
| |
| SPINAL OSTEOARTHRITIS | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
| |
| HEADACHE | Nervous system disorders | MedDRA 10.X | Systematic Assessment |
| |
| MIGRAINE | Nervous system disorders | MedDRA 10.X | Systematic Assessment |
| |
| DEPRESSION | Psychiatric disorders | MedDRA 10.X | Systematic Assessment |
| |
| SLEEP DISORDER | Psychiatric disorders | MedDRA 10.X | Systematic Assessment |
| |
| ATROPHIC VULVOVAGINITIS | Reproductive system and breast disorders | MedDRA 10.X | Systematic Assessment |
| |
| VAGINAL DISCHARGE | Reproductive system and breast disorders | MedDRA 10.X | Systematic Assessment |
| |
| COUGH | Respiratory, thoracic and mediastinal disorders | MedDRA 10.X | Systematic Assessment |
| |
| DYSPNOEA | Respiratory, thoracic and mediastinal disorders | MedDRA 10.X | Systematic Assessment |
| |
| ALOPECIA | Skin and subcutaneous tissue disorders | MedDRA 10.X | Systematic Assessment |
| |
| HYPERHIDROSIS | Skin and subcutaneous tissue disorders | MedDRA 10.X | Systematic Assessment |
| |
| HOT FLUSH | Vascular disorders | MedDRA 10.X | Systematic Assessment |
| |
| LYMPHOEDEMA | Vascular disorders | MedDRA 10.X | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial; or disclosure of the trial results in their entirety.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 |
| ID | Term |
|---|---|
| D010024 | Osteoporosis |
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D001851 | Bone Diseases, Metabolic |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077289 | Letrozole |
| D000077211 | Zoledronic Acid |
| ID | Term |
|---|---|
| D009570 | Nitriles |
| D009930 | Organic Chemicals |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D004164 | Diphosphonates |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D007093 | Imidazoles |
Not provided
Not provided
| >=65 years |
|
| Male |
|
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|
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|
|
|