Trial Outcomes & Findings for Safety/Efficacy of Letrozole Monotherapy or in Combination With Zoledronic Acid as Extended Adjuvant Treatment of Postmenopausal Patients With Primary Breast Cancer (NCT NCT00332709)
NCT ID: NCT00332709
Last Updated: 2011-11-16
Results Overview
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.
COMPLETED
PHASE3
83 participants
at 36 months as compared to baseline
2011-11-16
Participant Flow
Total Randomized participants were 83. 2 patients were enrolled but never received study medication. Hence, 81 were included in the safety population.
Participant milestones
| Measure |
Letrozole
Letrozole 2.5 mg/day for 3 years
|
Letrozole + Zoledronic Acid
Letrozole 2.5mg/day for 3 years plus Zoledronic acid 4mg every 6 months
|
|---|---|---|
|
Overall Study
STARTED
|
40
|
41
|
|
Overall Study
COMPLETED
|
24
|
21
|
|
Overall Study
NOT COMPLETED
|
16
|
20
|
Reasons for withdrawal
| Measure |
Letrozole
Letrozole 2.5 mg/day for 3 years
|
Letrozole + Zoledronic Acid
Letrozole 2.5mg/day for 3 years plus Zoledronic acid 4mg every 6 months
|
|---|---|---|
|
Overall Study
Adverse Event
|
11
|
14
|
|
Overall Study
Withdrawal by Subject
|
2
|
3
|
|
Overall Study
Lost to Follow-up
|
2
|
0
|
|
Overall Study
Administrative Problems
|
0
|
3
|
|
Overall Study
Abnormal test procedure result
|
1
|
0
|
Baseline Characteristics
Safety/Efficacy of Letrozole Monotherapy or in Combination With Zoledronic Acid as Extended Adjuvant Treatment of Postmenopausal Patients With Primary Breast Cancer
Baseline characteristics by cohort
| Measure |
Letrozole
n=37 Participants
Letrozole 2.5 mg/day for 3 years
|
Letrozole + Zoledronic Acid
n=39 Participants
Letrozole 2.5mg/day for 3 years plus Zoledronic acid 4mg every 6 months
|
Total
n=76 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
37 Participants
n=93 Participants
|
39 Participants
n=4 Participants
|
76 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age Continuous
|
61.3 years
STANDARD_DEVIATION 7.3 • n=93 Participants
|
58.4 years
STANDARD_DEVIATION 7.3 • n=4 Participants
|
59.8 years
STANDARD_DEVIATION 7.4 • n=27 Participants
|
|
Sex: Female, Male
Female
|
37 Participants
n=93 Participants
|
39 Participants
n=4 Participants
|
76 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: at 36 months as compared to baselinePopulation: (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.
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.
Outcome measures
| Measure |
Letrozole
n=21 Participants
Letrozole 2.5 mg/day for 3 years
|
Letrozole + Zoledronic Acid
n=20 Participants
Letrozole 2.5mg/day for 3 years plus Zoledronic acid 4mg every 6 months
|
|---|---|---|
|
Change in Bone Mineral Density (BMD) From Baseline to Month 36
|
-0.11 Percent
Standard Deviation 0.14
|
0.03 Percent
Standard Deviation 0.08
|
PRIMARY outcome
Timeframe: Baseline, Month 36Population: (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.
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.
Outcome measures
| Measure |
Letrozole
n=21 Participants
Letrozole 2.5 mg/day for 3 years
|
Letrozole + Zoledronic Acid
n=20 Participants
Letrozole 2.5mg/day for 3 years plus Zoledronic acid 4mg every 6 months
|
|---|---|---|
|
Percent Change in Bone Mineral Density (BMD) From Baseline to Month 36
|
-11.34 Percent Change in BMD
Standard Deviation 17.72
|
3.31 Percent Change in BMD
Standard Deviation 8.32
|
PRIMARY outcome
Timeframe: Baseline and Month 36Population: (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.
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.
Outcome measures
| Measure |
Letrozole
n=20 Participants
Letrozole 2.5 mg/day for 3 years
|
Letrozole + Zoledronic Acid
n=21 Participants
Letrozole 2.5mg/day for 3 years plus Zoledronic acid 4mg every 6 months
|
|---|---|---|
|
Change in T-score From Baseline to Month 36
|
-0.90 T-Score
Standard Deviation 1.03
|
0.46 T-Score
Standard Deviation 0.27
|
PRIMARY outcome
Timeframe: Baseline, month 36Population: (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.
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.
Outcome measures
| Measure |
Letrozole
n=22 Participants
Letrozole 2.5 mg/day for 3 years
|
Letrozole + Zoledronic Acid
n=20 Participants
Letrozole 2.5mg/day for 3 years plus Zoledronic acid 4mg every 6 months
|
|---|---|---|
|
Change in Z Score From Baseline to Month 36
|
-0.31 Z-Score
Standard Deviation 0.35
|
0.25 Z-Score
Standard Deviation 0.34
|
SECONDARY outcome
Timeframe: Baseline, 12 monthsPopulation: (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.
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.
Outcome measures
| Measure |
Letrozole
n=23 Participants
Letrozole 2.5 mg/day for 3 years
|
Letrozole + Zoledronic Acid
n=23 Participants
Letrozole 2.5mg/day for 3 years plus Zoledronic acid 4mg every 6 months
|
|---|---|---|
|
Change in Bone Mineral Density From Baseline to 12 Months
|
-0.04 g/cm^2
Standard Deviation 0.04
|
0.02 g/cm^2
Standard Deviation 0.05
|
SECONDARY outcome
Timeframe: Baseline, Month 6, 12, 18, 24 , 30 and 36Population: (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.
Number of participants with fractures of any type since the last visit
Outcome measures
| Measure |
Letrozole
n=21 Participants
Letrozole 2.5 mg/day for 3 years
|
Letrozole + Zoledronic Acid
n=20 Participants
Letrozole 2.5mg/day for 3 years plus Zoledronic acid 4mg every 6 months
|
|---|---|---|
|
Number of Participants With Any Kind of Fractures, by Visit.
Baseline
|
0 Participants
|
0 Participants
|
|
Number of Participants With Any Kind of Fractures, by Visit.
Month 6
|
0 Participants
|
0 Participants
|
|
Number of Participants With Any Kind of Fractures, by Visit.
Month 12
|
0 Participants
|
0 Participants
|
|
Number of Participants With Any Kind of Fractures, by Visit.
Month 18
|
0 Participants
|
0 Participants
|
|
Number of Participants With Any Kind of Fractures, by Visit.
Month 24
|
0 Participants
|
0 Participants
|
|
Number of Participants With Any Kind of Fractures, by Visit.
Month 30
|
0 Participants
|
0 Participants
|
|
Number of Participants With Any Kind of Fractures, by Visit.
Month 36
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 36 monthsPopulation: (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.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Month 12Population: (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.
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.
Outcome measures
| Measure |
Letrozole
n=23 Participants
Letrozole 2.5 mg/day for 3 years
|
Letrozole + Zoledronic Acid
n=24 Participants
Letrozole 2.5mg/day for 3 years plus Zoledronic acid 4mg every 6 months
|
|---|---|---|
|
Change in T-Score From Baseline to Month 12
|
-0.31 T-Score
Standard Deviation 0.35
|
0.25 T-Score
Standard Deviation 0.34
|
SECONDARY outcome
Timeframe: Baseline, Month 12Population: (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
(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
Outcome measures
| Measure |
Letrozole
n=23 Participants
Letrozole 2.5 mg/day for 3 years
|
Letrozole + Zoledronic Acid
n=22 Participants
Letrozole 2.5mg/day for 3 years plus Zoledronic acid 4mg every 6 months
|
|---|---|---|
|
Change in Z-Score From Baseline to Month 12
|
-0.26 Z-Score
Standard Deviation 0.35
|
0.37 Z-Score
Standard Deviation 0.38
|
Adverse Events
Letrozole
Letrozole + Zolendronic Acid
Serious adverse events
| Measure |
Letrozole
n=40 participants at risk
Letrozole orally 2.5 mg/day for 3 years
|
Letrozole + Zolendronic Acid
n=41 participants at risk
Letrozole 2.5mg/day for 3 years plus Zoledronic acid 4mg every 6 months
|
|---|---|---|
|
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION
|
0.00%
0/40
|
2.4%
1/41
|
|
Cardiac disorders
ANGINA PECTORIS
|
0.00%
0/40
|
2.4%
1/41
|
|
Cardiac disorders
ANGINA UNSTABLE
|
0.00%
0/40
|
2.4%
1/41
|
|
Cardiac disorders
CORONARY ARTERY STENOSIS
|
0.00%
0/40
|
2.4%
1/41
|
|
Cardiac disorders
SUPRAVENTRICULAR TACHYCARDIA
|
0.00%
0/40
|
2.4%
1/41
|
|
Ear and labyrinth disorders
VERTIGO POSITIONAL
|
2.5%
1/40
|
0.00%
0/41
|
|
General disorders
CONCOMITANT DISEASE PROGRESSION
|
2.5%
1/40
|
0.00%
0/41
|
|
Hepatobiliary disorders
CHOLECYSTITIS
|
2.5%
1/40
|
0.00%
0/41
|
|
Infections and infestations
DIVERTICULITIS
|
0.00%
0/40
|
2.4%
1/41
|
|
Injury, poisoning and procedural complications
CONTUSION
|
0.00%
0/40
|
2.4%
1/41
|
|
Injury, poisoning and procedural complications
FALL
|
2.5%
1/40
|
0.00%
0/41
|
|
Injury, poisoning and procedural complications
LOWER LIMB FRACTURE
|
2.5%
1/40
|
0.00%
0/41
|
|
Injury, poisoning and procedural complications
ROAD TRAFFIC ACCIDENT
|
0.00%
0/40
|
2.4%
1/41
|
|
Injury, poisoning and procedural complications
VASCULAR PSEUDOANEURYSM
|
0.00%
0/40
|
2.4%
1/41
|
|
Investigations
OXYGEN SATURATION DECREASED
|
0.00%
0/40
|
2.4%
1/41
|
|
Musculoskeletal and connective tissue disorders
AXILLARY MASS
|
2.5%
1/40
|
0.00%
0/41
|
|
Musculoskeletal and connective tissue disorders
COMPARTMENT SYNDROME
|
0.00%
0/40
|
2.4%
1/41
|
|
Musculoskeletal and connective tissue disorders
OSTEOARTHRITIS
|
2.5%
1/40
|
2.4%
1/41
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTASES TO BONE
|
2.5%
1/40
|
0.00%
0/41
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTASES TO LIVER
|
2.5%
1/40
|
0.00%
0/41
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTASES TO LUNG
|
2.5%
1/40
|
0.00%
0/41
|
|
Reproductive system and breast disorders
VAGINAL HAEMORRHAGE
|
0.00%
0/40
|
2.4%
1/41
|
Other adverse events
| Measure |
Letrozole
n=40 participants at risk
Letrozole orally 2.5 mg/day for 3 years
|
Letrozole + Zolendronic Acid
n=41 participants at risk
Letrozole 2.5mg/day for 3 years plus Zoledronic acid 4mg every 6 months
|
|---|---|---|
|
Ear and labyrinth disorders
VERTIGO
|
5.0%
2/40
|
4.9%
2/41
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
0.00%
0/40
|
9.8%
4/41
|
|
Gastrointestinal disorders
CONSTIPATION
|
7.5%
3/40
|
0.00%
0/41
|
|
Gastrointestinal disorders
DIARRHOEA
|
5.0%
2/40
|
7.3%
3/41
|
|
Gastrointestinal disorders
DRY MOUTH
|
7.5%
3/40
|
7.3%
3/41
|
|
Gastrointestinal disorders
DYSPEPSIA
|
5.0%
2/40
|
2.4%
1/41
|
|
Gastrointestinal disorders
NAUSEA
|
0.00%
0/40
|
17.1%
7/41
|
|
General disorders
CHILLS
|
2.5%
1/40
|
17.1%
7/41
|
|
General disorders
FATIGUE
|
5.0%
2/40
|
29.3%
12/41
|
|
General disorders
INFLUENZA LIKE ILLNESS
|
0.00%
0/40
|
7.3%
3/41
|
|
General disorders
OEDEMA PERIPHERAL
|
10.0%
4/40
|
7.3%
3/41
|
|
General disorders
PYREXIA
|
0.00%
0/40
|
22.0%
9/41
|
|
Hepatobiliary disorders
HEPATIC CYST
|
7.5%
3/40
|
0.00%
0/41
|
|
Infections and infestations
CYSTITIS
|
5.0%
2/40
|
0.00%
0/41
|
|
Infections and infestations
NASOPHARYNGITIS
|
7.5%
3/40
|
9.8%
4/41
|
|
Metabolism and nutrition disorders
DECREASED APPETITE
|
0.00%
0/40
|
7.3%
3/41
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
27.5%
11/40
|
34.1%
14/41
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
5.0%
2/40
|
12.2%
5/41
|
|
Musculoskeletal and connective tissue disorders
BONE PAIN
|
30.0%
12/40
|
34.1%
14/41
|
|
Musculoskeletal and connective tissue disorders
MUSCLE SPASMS
|
5.0%
2/40
|
0.00%
0/41
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
|
0.00%
0/40
|
14.6%
6/41
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
5.0%
2/40
|
4.9%
2/41
|
|
Musculoskeletal and connective tissue disorders
NECK PAIN
|
0.00%
0/40
|
12.2%
5/41
|
|
Musculoskeletal and connective tissue disorders
OSTEOARTHRITIS
|
5.0%
2/40
|
2.4%
1/41
|
|
Musculoskeletal and connective tissue disorders
OSTEOPENIA
|
12.5%
5/40
|
0.00%
0/41
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
12.5%
5/40
|
24.4%
10/41
|
|
Musculoskeletal and connective tissue disorders
SPINAL OSTEOARTHRITIS
|
5.0%
2/40
|
0.00%
0/41
|
|
Nervous system disorders
HEADACHE
|
12.5%
5/40
|
22.0%
9/41
|
|
Nervous system disorders
MIGRAINE
|
5.0%
2/40
|
2.4%
1/41
|
|
Psychiatric disorders
DEPRESSION
|
5.0%
2/40
|
2.4%
1/41
|
|
Psychiatric disorders
SLEEP DISORDER
|
5.0%
2/40
|
7.3%
3/41
|
|
Reproductive system and breast disorders
ATROPHIC VULVOVAGINITIS
|
7.5%
3/40
|
0.00%
0/41
|
|
Reproductive system and breast disorders
VAGINAL DISCHARGE
|
5.0%
2/40
|
0.00%
0/41
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
5.0%
2/40
|
7.3%
3/41
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
0.00%
0/40
|
9.8%
4/41
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
15.0%
6/40
|
14.6%
6/41
|
|
Skin and subcutaneous tissue disorders
HYPERHIDROSIS
|
2.5%
1/40
|
7.3%
3/41
|
|
Vascular disorders
HOT FLUSH
|
22.5%
9/40
|
22.0%
9/41
|
|
Vascular disorders
LYMPHOEDEMA
|
5.0%
2/40
|
4.9%
2/41
|
Additional Information
Study Director
Novartis Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER