Trial Outcomes & Findings for Safety and Efficacy of Zoledronic Acid in Patients With Breast Cancer With Metastatic Bone Lesions (NCT NCT00375427)
NCT ID: NCT00375427
Last Updated: 2012-04-11
Results Overview
The SMR was computed by summing all Skeletal Related Event(s) (SREs)which occurred during the observation period and dividing it by the ratio "days of observation period / 365.25", for each participant. SRE was defined as: pathologic bone fracture, spinal cord compression, surgery to bone both curative and prophylactic, radiation therapy to bone, or hypercalcemia of malignancy. SMR (years) = 365.25 x SMR(days) where SMR (days) = total number of SREs / total SRE risk period (days). Risk period for SMR was computed as the days from randomization date to the date of last visit.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
430 participants
Primary outcome timeframe
12 months
Results posted on
2012-04-11
Participant Flow
Total enrollment was 430; five participants were screened but not treated.
Participant milestones
| Measure |
Zoledronic Acid Every 3 Months
Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group.
|
Zoledronic Acid Every 4 Weeks
Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions.
|
|---|---|---|
|
Overall Study
STARTED
|
209
|
216
|
|
Overall Study
COMPLETED
|
149
|
142
|
|
Overall Study
NOT COMPLETED
|
60
|
74
|
Reasons for withdrawal
| Measure |
Zoledronic Acid Every 3 Months
Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group.
|
Zoledronic Acid Every 4 Weeks
Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions.
|
|---|---|---|
|
Overall Study
Adverse Event
|
21
|
27
|
|
Overall Study
Abnormal test procedure result(s)
|
0
|
1
|
|
Overall Study
Abnormal laboratory value(s)
|
1
|
2
|
|
Overall Study
Unsatisfactory therapeutic effect
|
4
|
4
|
|
Overall Study
Patient no longer requires study drug
|
3
|
7
|
|
Overall Study
Protocol Violation
|
10
|
8
|
|
Overall Study
Withdrawal by Subject
|
9
|
13
|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
|
Overall Study
Administrative reasons
|
0
|
1
|
|
Overall Study
Death
|
11
|
10
|
Baseline Characteristics
Safety and Efficacy of Zoledronic Acid in Patients With Breast Cancer With Metastatic Bone Lesions
Baseline characteristics by cohort
| Measure |
Zoledronic Acid Every 3 Months
n=209 Participants
Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group.
|
Zoledronic Acid Every 4 Weeks
n=216 Participants
Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions.
|
Total
n=425 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
60.4 years
STANDARD_DEVIATION 11.9 • n=5 Participants
|
59.8 years
STANDARD_DEVIATION 11.8 • n=7 Participants
|
60.1 years
STANDARD_DEVIATION 11.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
209 Participants
n=5 Participants
|
216 Participants
n=7 Participants
|
425 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 monthsPopulation: Intent-to-treat (ITT) population will include all randomized patients.
The SMR was computed by summing all Skeletal Related Event(s) (SREs)which occurred during the observation period and dividing it by the ratio "days of observation period / 365.25", for each participant. SRE was defined as: pathologic bone fracture, spinal cord compression, surgery to bone both curative and prophylactic, radiation therapy to bone, or hypercalcemia of malignancy. SMR (years) = 365.25 x SMR(days) where SMR (days) = total number of SREs / total SRE risk period (days). Risk period for SMR was computed as the days from randomization date to the date of last visit.
Outcome measures
| Measure |
Zoledronic Acid Every 3 Months
n=209 Participants
Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group.
|
Zoledronic Acid Every 4 Weeks
n=216 Participants
Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions.
|
|---|---|---|
|
Annual Overall Skeletal Morbidity Rate (SMR)
|
0.26 Number of Skeletal Events per Year
Standard Deviation 0.81
|
0.22 Number of Skeletal Events per Year
Standard Deviation 0.57
|
SECONDARY outcome
Timeframe: 12 monthPopulation: Intent-to-treat (ITT) population will include all randomized patients.
Skeletal Related Events (SREs) are defined as a: * pathologic bone fracture such as non-vertebral and vertebral compression fractures * spinal cord compression identified by positive diagnosis documented by X-ray evidence * surgery to bone both curative and prophylactic * radiation therapy to bone including palliative, therapeutic or prophylactic * hypercalcemia of malignancy, defined as a corrected serum calcium \> 12 mg/dl (3.00 mmol/l) or a lower level of hypercalcemia which is symptomatic and which requires active treatment other than rehydration.
Outcome measures
| Measure |
Zoledronic Acid Every 3 Months
n=209 Participants
Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group.
|
Zoledronic Acid Every 4 Weeks
n=216 Participants
Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions.
|
|---|---|---|
|
Percentage of Participants Experiencing Skeletal Related Event(s) (SREs)
Vertebral pathological fracture
|
1.44 Percentage of Participants
|
1.85 Percentage of Participants
|
|
Percentage of Participants Experiencing Skeletal Related Event(s) (SREs)
Non vertebral pathological fracture
|
3.35 Percentage of Participants
|
2.31 Percentage of Participants
|
|
Percentage of Participants Experiencing Skeletal Related Event(s) (SREs)
Radiation to bone
|
10.53 Percentage of Participants
|
11.11 Percentage of Participants
|
|
Percentage of Participants Experiencing Skeletal Related Event(s) (SREs)
Surgery to bone
|
0.96 Percentage of Participants
|
0.46 Percentage of Participants
|
|
Percentage of Participants Experiencing Skeletal Related Event(s) (SREs)
Patient with any SRE
|
14.83 Percentage of Participants
|
15.28 Percentage of Participants
|
|
Percentage of Participants Experiencing Skeletal Related Event(s) (SREs)
Spinal cord compression
|
0.96 Percentage of Participants
|
0.46 Percentage of Participants
|
|
Percentage of Participants Experiencing Skeletal Related Event(s) (SREs)
Hypercalcemia of malignancy
|
0.48 Percentage of Participants
|
1.85 Percentage of Participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Intent-to-treat (ITT) population will include all randomized patients.
Skeletal Related Events (SREs) are defined as a: * pathologic bone fracture such as non-vertebral and vertebral * spinal cord compression identified by X-rays evidence * surgery to bone both curative and prophylactic * radiation therapy to bone including palliative, therapeutic or prophylactic * hypercalcemia of malignancy, defined as a corrected serum calcium \> 12 mg/dl (3.00 mmol/l) or a lower level of hypercalcemia which is symptomatic and which requires active treatment other than rehydration. Annual incidence for each SRE was computed in the same way as annual overall SMR.
Outcome measures
| Measure |
Zoledronic Acid Every 3 Months
n=209 Participants
Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group.
|
Zoledronic Acid Every 4 Weeks
n=216 Participants
Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions.
|
|---|---|---|
|
Annual Incidence of Any Skeletal Related Events (SREs)
Vertebral pathological fracture rate
|
0.02 Number of SRE per Year
Standard Deviation 0.19
|
0.02 Number of SRE per Year
Standard Deviation 0.15
|
|
Annual Incidence of Any Skeletal Related Events (SREs)
Non-vertebral pathological fracture rate
|
0.08 Number of SRE per Year
Standard Deviation 0.58
|
0.03 Number of SRE per Year
Standard Deviation 0.20
|
|
Annual Incidence of Any Skeletal Related Events (SREs)
Spinal cord compression rate
|
0.01 Number of SRE per Year
Standard Deviation 0.10
|
0.00 Number of SRE per Year
Standard Deviation 0.07
|
|
Annual Incidence of Any Skeletal Related Events (SREs)
Radiation to bone rate
|
0.17 Number of SRE per Year
Standard Deviation 0.67
|
0.14 Number of SRE per Year
Standard Deviation 0.43
|
|
Annual Incidence of Any Skeletal Related Events (SREs)
Surgery to bone rate
|
0.02 Number of SRE per Year
Standard Deviation 0.21
|
0.00 Number of SRE per Year
Standard Deviation 0.07
|
|
Annual Incidence of Any Skeletal Related Events (SREs)
Hypercalcemia of malignancy rate
|
0.01 Number of SRE per Year
Standard Deviation 0.08
|
0.02 Number of SRE per Year
Standard Deviation 0.16
|
SECONDARY outcome
Timeframe: 12 monthMedian Time to first skeletal related event (SRE) is defined as the time from randomization to the date of first occurrence of any SRE which includes at least one of the following: radiation therapy to bone, pathologic bone fracture, spinal cord compression, surgery to bone, and hypercalcemia of malignancy (HCM). Due to the few numbers of SRE, Kaplan-Meier estimate never reaches a failure probability \>=25%; so median time, 25th and 75th percentiles are not determined.For this reason only the estimated percentage of patient SRE free are reported at each time point.
Outcome measures
| Measure |
Zoledronic Acid Every 3 Months
n=209 Participants
Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group.
|
Zoledronic Acid Every 4 Weeks
n=216 Participants
Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions.
|
|---|---|---|
|
Median Time to First Skeletal Related Event(s) (SRE)
|
NA Day
NA=Not evaluable. Due to the low incidence of SRE, K-M estimates never reach a failure probability ≥25%; so median time, 25th and 75th percentiles aren't determined. Time can't be estimated because of insufficient SRE to reach the quartiles
|
NA Day
NA=Not evaluable. Due to the low incidence of SRE, K-M estimates never reach a failure probability ≥25%; so median time, 25th and 75th percentiles aren't determined. Time can't be estimated because of insufficient SRE to reach the quartiles
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Intent-to-treat (ITT) population will include all randomized patients.
Percentage of participants SRE free is defined as the Kaplan-Meier estimate of participants free of any Skeletal Related Events(SRE) at each time point. Skeletal Related Events (SREs) are: * pathologic bone fracture; non-vertebral and vertebral * spinal cord compression identified by X-rays * surgery to bone both curative and prophylactic * radiation therapy to bone (palliative, therapeutic or prophylactic) * hypercalcemia of malignancy, defined as a corrected serum calcium \> 12 mg/dl (3.00 mmol/l) or a lower level which is symptomatic and requires treatment other than rehydration.
Outcome measures
| Measure |
Zoledronic Acid Every 3 Months
n=209 Participants
Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group.
|
Zoledronic Acid Every 4 Weeks
n=216 Participants
Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions.
|
|---|---|---|
|
Percentage of Participants Skeletal Related Event (SRE) Free
At Month 1
|
99 Percentage of participants
Interval 96.0 to 100.0
|
98 Percentage of participants
Interval 95.0 to 99.0
|
|
Percentage of Participants Skeletal Related Event (SRE) Free
At Month 3
|
96 Percentage of participants
Interval 92.0 to 98.0
|
97 Percentage of participants
Interval 93.0 to 98.0
|
|
Percentage of Participants Skeletal Related Event (SRE) Free
At Month 4
|
94 Percentage of participants
Interval 90.0 to 97.0
|
95 Percentage of participants
Interval 91.0 to 97.0
|
|
Percentage of Participants Skeletal Related Event (SRE) Free
At Month 5
|
94 Percentage of participants
Interval 89.0 to 96.0
|
93 Percentage of participants
Interval 89.0 to 96.0
|
|
Percentage of Participants Skeletal Related Event (SRE) Free
At Month 7
|
88 Percentage of participants
Interval 83.0 to 92.0
|
90 Percentage of participants
Interval 85.0 to 93.0
|
|
Percentage of Participants Skeletal Related Event (SRE) Free
At Month 8
|
86 Percentage of participants
Interval 80.0 to 90.0
|
88 Percentage of participants
Interval 83.0 to 92.0
|
|
Percentage of Participants Skeletal Related Event (SRE) Free
At Month 9
|
85 Percentage of participants
Interval 79.0 to 90.0
|
85 Percentage of participants
Interval 79.0 to 89.0
|
|
Percentage of Participants Skeletal Related Event (SRE) Free
At Month 12
|
78 Percentage of participants
Interval 63.0 to 87.0
|
82 Percentage of participants
Interval 75.0 to 87.0
|
|
Percentage of Participants Skeletal Related Event (SRE) Free
At Month 2
|
98 Percentage of participants
Interval 94.0 to 99.0
|
98 Percentage of participants
Interval 94.0 to 99.0
|
|
Percentage of Participants Skeletal Related Event (SRE) Free
At Month 6
|
93 Percentage of participants
Interval 89.0 to 96.0
|
92 Percentage of participants
Interval 87.0 to 95.0
|
|
Percentage of Participants Skeletal Related Event (SRE) Free
At Month 10
|
84 Percentage of participants
Interval 78.0 to 89.0
|
83 Percentage of participants
Interval 77.0 to 88.0
|
|
Percentage of Participants Skeletal Related Event (SRE) Free
At Month 11
|
83 Percentage of participants
Interval 77.0 to 88.0
|
83 Percentage of participants
Interval 77.0 to 88.0
|
SECONDARY outcome
Timeframe: At Baseline, Month 3, Month 6, Month 9 and Month 12Population: Intent-to-treat (ITT) population will include all randomized patients. All ITT patients with BPI questionnaire filled up at baseline were included.
Bone pain was assessed by means of a pain score obtained using the Brief Pain Inventory (BPI) questionnaire. The BPI can produce three pain scores: worst pain, a composite pain score, and a pain interference score. The composite pain score, which is the average of questions 3, 4, 5 and 6 of the questionnaire was used in this study. Pain was rated on a scale of 0 (no pain) to 10 (pain as bad as you can imagine). The outcome is given as the median score for participants at baseline, and 3, 6, 9 and 12 months of treatment
Outcome measures
| Measure |
Zoledronic Acid Every 3 Months
n=186 Participants
Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group.
|
Zoledronic Acid Every 4 Weeks
n=185 Participants
Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions.
|
|---|---|---|
|
Composite Bone Pain Score According to the Brief Pain Inventory (BPI) Questionnaire
Baseline (N= 186, 185)
|
2.0 score on a scale
Standard Deviation 1.8
|
2.1 score on a scale
Standard Deviation 1.9
|
|
Composite Bone Pain Score According to the Brief Pain Inventory (BPI) Questionnaire
Month 3 (N= 156, 163)
|
2.3 score on a scale
Standard Deviation 2.0
|
2.2 score on a scale
Standard Deviation 1.9
|
|
Composite Bone Pain Score According to the Brief Pain Inventory (BPI) Questionnaire
Month 9 (N= 131, 130)
|
2.3 score on a scale
Standard Deviation 2.2
|
2.1 score on a scale
Standard Deviation 2.0
|
|
Composite Bone Pain Score According to the Brief Pain Inventory (BPI) Questionnaire
Month 12 (N= 135, 124)
|
2.4 score on a scale
Standard Deviation 2.3
|
2.1 score on a scale
Standard Deviation 2.0
|
|
Composite Bone Pain Score According to the Brief Pain Inventory (BPI) Questionnaire
Month 6 (N= 143, 160)
|
2.3 score on a scale
Standard Deviation 2.2
|
1.9 score on a scale
Standard Deviation 1.8
|
SECONDARY outcome
Timeframe: At Baseline, Month 3, Month 6, Month 9 and Month 12Population: Intent-to-treat (ITT) population will include all randomized patients.
Pain intensity at rest and on movement is rated by the patient by means of a validated 6-point Verbal Rating Scale (VRS) and refers to the pain which occurred during the last week before the assessment. Median score value is the median of all the observed scores (none=0, very mild=1, mild=2, moderate=3, severe=5 and very severe=6) at each time point.
Outcome measures
| Measure |
Zoledronic Acid Every 3 Months
n=209 Participants
Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group.
|
Zoledronic Acid Every 4 Weeks
n=216 Participants
Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions.
|
|---|---|---|
|
Evaluation of Pain According to Verbal Rating Scale (VRS) Based on Median Score Value
At Rest: Month 6
|
2 score on a scale
Interval 1.0 to 5.0
|
1 score on a scale
Interval 1.0 to 6.0
|
|
Evaluation of Pain According to Verbal Rating Scale (VRS) Based on Median Score Value
At Rest: Month 9
|
1 score on a scale
Interval 1.0 to 5.0
|
1 score on a scale
Interval 1.0 to 5.0
|
|
Evaluation of Pain According to Verbal Rating Scale (VRS) Based on Median Score Value
At Rest: Month 12
|
2 score on a scale
Interval 1.0 to 6.0
|
1 score on a scale
Interval 1.0 to 6.0
|
|
Evaluation of Pain According to Verbal Rating Scale (VRS) Based on Median Score Value
At Movement : Baseline
|
2 score on a scale
Interval 1.0 to 5.0
|
2 score on a scale
Interval 1.0 to 6.0
|
|
Evaluation of Pain According to Verbal Rating Scale (VRS) Based on Median Score Value
At Movement : Month 3
|
2 score on a scale
Interval 1.0 to 6.0
|
2 score on a scale
Interval 1.0 to 6.0
|
|
Evaluation of Pain According to Verbal Rating Scale (VRS) Based on Median Score Value
At Movement : Month 6
|
2 score on a scale
Interval 1.0 to 6.0
|
2 score on a scale
Interval 1.0 to 6.0
|
|
Evaluation of Pain According to Verbal Rating Scale (VRS) Based on Median Score Value
At Movement : Month 9
|
2 score on a scale
Interval 1.0 to 6.0
|
2 score on a scale
Interval 1.0 to 6.0
|
|
Evaluation of Pain According to Verbal Rating Scale (VRS) Based on Median Score Value
At Movement : Month 12
|
2.5 score on a scale
Interval 1.0 to 6.0
|
2 score on a scale
Interval 1.0 to 6.0
|
|
Evaluation of Pain According to Verbal Rating Scale (VRS) Based on Median Score Value
At Rest: Baseline
|
1 score on a scale
Interval 1.0 to 5.0
|
1 score on a scale
Interval 1.0 to 6.0
|
|
Evaluation of Pain According to Verbal Rating Scale (VRS) Based on Median Score Value
At Rest: Month 3
|
2 score on a scale
Interval 1.0 to 6.0
|
2 score on a scale
Interval 1.0 to 5.0
|
SECONDARY outcome
Timeframe: At Baseline, Month 3, Month 6, Month 9 and Month 12Population: Intent-to-treat (ITT) population will include all randomized patients.
The analgesic score used for this study is modified from the Radiation Therapy Oncology Group (RTOG) analgesic score scale. The scale represents type of medication administered from 0 to 4 where: 0 = None 1. = Minor analgesics (aspirin, NSAID, acetaminophen, propoxyphene, etc.) 2. = Tranquilisers, antidepressants, muscle relaxants, and steroids 3. = Mild narcotics (oxycodone, meperidine, codeine, etc.) 4. = Strong narcotics (morphine, hydromorphone, etc.) The outcome is given a the median score for the participants at Baseline and 3, 6, 9 and 12 months of treatment
Outcome measures
| Measure |
Zoledronic Acid Every 3 Months
n=209 Participants
Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group.
|
Zoledronic Acid Every 4 Weeks
n=216 Participants
Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions.
|
|---|---|---|
|
Use Of Analgesic Medications According to the Analgesic Score Scale
Month 9
|
0 score on a scale
Interval 0.0 to 4.0
|
0 score on a scale
Interval 0.0 to 4.0
|
|
Use Of Analgesic Medications According to the Analgesic Score Scale
Month 12
|
0 score on a scale
Interval 0.0 to 4.0
|
0 score on a scale
Interval 0.0 to 4.0
|
|
Use Of Analgesic Medications According to the Analgesic Score Scale
Baseline
|
0 score on a scale
Interval 0.0 to 4.0
|
0 score on a scale
Interval 0.0 to 4.0
|
|
Use Of Analgesic Medications According to the Analgesic Score Scale
Month 3
|
0 score on a scale
Interval 0.0 to 4.0
|
0 score on a scale
Interval 0.0 to 4.0
|
|
Use Of Analgesic Medications According to the Analgesic Score Scale
Month 6
|
0 score on a scale
Interval 0.0 to 4.0
|
0 score on a scale
Interval 0.0 to 4.0
|
SECONDARY outcome
Timeframe: At Baseline, Month 3, Month 6, Month 9 and Month 12Population: Intent-to-treat (ITT) population will include all randomized patients.
ECOG Performance Score has 4 grades. 0 = Fully active, able to carry out all pre-disease activities; 1 = Restricted in strenuous activity but ambulatory and able to carry out work of light or sedentary nature; 2 = Ambulatory and capable of all self-care but unable to carry out work activities. Active about 50% of waking hours; 3 = Capable of limited self-care, confined to bed/chair more than 50% of waking hours; 4 = Completely disabled; cannot carry on self-care. Totally confined to bed/chair. Outcome is given as median score for participants at Baseline and 3, 6 , 9 and 12 months of treatment
Outcome measures
| Measure |
Zoledronic Acid Every 3 Months
n=209 Participants
Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group.
|
Zoledronic Acid Every 4 Weeks
n=216 Participants
Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions.
|
|---|---|---|
|
Assessment of the Eastern Cooperative Oncology Group (ECOG) Performance Score
Month 3
|
0 score on a scale
Interval 0.0 to 3.0
|
0 score on a scale
Interval 0.0 to 3.0
|
|
Assessment of the Eastern Cooperative Oncology Group (ECOG) Performance Score
Baseline
|
0 score on a scale
Interval 0.0 to 2.0
|
0 score on a scale
Interval 0.0 to 2.0
|
|
Assessment of the Eastern Cooperative Oncology Group (ECOG) Performance Score
Month 6
|
0 score on a scale
Interval 0.0 to 2.0
|
0 score on a scale
Interval 0.0 to 2.0
|
|
Assessment of the Eastern Cooperative Oncology Group (ECOG) Performance Score
Month 9
|
0 score on a scale
Interval 0.0 to 2.0
|
0 score on a scale
Interval 0.0 to 2.0
|
|
Assessment of the Eastern Cooperative Oncology Group (ECOG) Performance Score
Month 12
|
0 score on a scale
Interval 0.0 to 4.0
|
0 score on a scale
Interval 0.0 to 4.0
|
Adverse Events
Zoledronic Acid Every 3 Months
Serious events: 21 serious events
Other events: 133 other events
Deaths: 0 deaths
Zoledronic Acid Every 4 Weeks
Serious events: 29 serious events
Other events: 161 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Zoledronic Acid Every 3 Months
n=209 participants at risk
Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group.
|
Zoledronic Acid Every 4 Weeks
n=216 participants at risk
Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/209
|
0.93%
2/216
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/209
|
0.93%
2/216
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/209
|
0.93%
2/216
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/209
|
0.46%
1/216
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/209
|
0.46%
1/216
|
|
Eye disorders
Diplopia
|
0.00%
0/209
|
0.46%
1/216
|
|
Gastrointestinal disorders
Gastric haemorrhage
|
0.00%
0/209
|
0.46%
1/216
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/209
|
0.46%
1/216
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/209
|
0.93%
2/216
|
|
Gastrointestinal disorders
Vomiting
|
0.48%
1/209
|
0.93%
2/216
|
|
General disorders
Mucosal inflammation
|
0.00%
0/209
|
0.46%
1/216
|
|
General disorders
Pain
|
0.48%
1/209
|
0.00%
0/216
|
|
Hepatobiliary disorders
Jaundice
|
0.00%
0/209
|
0.46%
1/216
|
|
Infections and infestations
Acute sinusitis
|
0.48%
1/209
|
0.00%
0/216
|
|
Infections and infestations
Pneumonia
|
0.00%
0/209
|
0.46%
1/216
|
|
Infections and infestations
Sepsis
|
0.00%
0/209
|
0.46%
1/216
|
|
Infections and infestations
Skin infection
|
0.00%
0/209
|
0.46%
1/216
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.96%
2/209
|
0.46%
1/216
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/209
|
0.46%
1/216
|
|
Metabolism and nutrition disorders
Cachexia
|
0.48%
1/209
|
0.46%
1/216
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/209
|
0.46%
1/216
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.48%
1/209
|
0.93%
2/216
|
|
Musculoskeletal and connective tissue disorders
Jaw disorder
|
0.00%
0/209
|
0.46%
1/216
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.48%
1/209
|
0.00%
0/216
|
|
Musculoskeletal and connective tissue disorders
Osteitis
|
0.00%
0/209
|
0.46%
1/216
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
1.9%
4/209
|
1.4%
3/216
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
0.96%
2/209
|
0.46%
1/216
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
0.48%
1/209
|
0.00%
0/216
|
|
Nervous system disorders
Cranial nerve paralysis
|
0.00%
0/209
|
0.46%
1/216
|
|
Nervous system disorders
Epilepsy
|
0.48%
1/209
|
0.00%
0/216
|
|
Nervous system disorders
Ischaemic cerebral infarction
|
0.00%
0/209
|
0.46%
1/216
|
|
Nervous system disorders
Paraparesis
|
0.00%
0/209
|
0.46%
1/216
|
|
Psychiatric disorders
Depression
|
0.48%
1/209
|
0.00%
0/216
|
|
Psychiatric disorders
Sopor
|
0.00%
0/209
|
0.46%
1/216
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.96%
2/209
|
0.93%
2/216
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.00%
0/209
|
0.46%
1/216
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/209
|
0.46%
1/216
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/209
|
0.46%
1/216
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.48%
1/209
|
0.00%
0/216
|
|
Surgical and medical procedures
Breast operation
|
0.48%
1/209
|
0.00%
0/216
|
|
Surgical and medical procedures
Laparoscopic surgery
|
0.00%
0/209
|
0.46%
1/216
|
|
Vascular disorders
Deep vein thrombosis
|
0.48%
1/209
|
0.46%
1/216
|
Other adverse events
| Measure |
Zoledronic Acid Every 3 Months
n=209 participants at risk
Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group.
|
Zoledronic Acid Every 4 Weeks
n=216 participants at risk
Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
6.2%
13/209
|
9.7%
21/216
|
|
Blood and lymphatic system disorders
Neutropenia
|
5.3%
11/209
|
8.3%
18/216
|
|
Ear and labyrinth disorders
Vertigo
|
0.96%
2/209
|
5.1%
11/216
|
|
Gastrointestinal disorders
Abdominal pain
|
5.7%
12/209
|
6.9%
15/216
|
|
Gastrointestinal disorders
Abdominal pain upper
|
7.7%
16/209
|
9.3%
20/216
|
|
Gastrointestinal disorders
Constipation
|
5.7%
12/209
|
6.9%
15/216
|
|
Gastrointestinal disorders
Diarrhoea
|
5.7%
12/209
|
7.9%
17/216
|
|
Gastrointestinal disorders
Nausea
|
11.5%
24/209
|
14.8%
32/216
|
|
Gastrointestinal disorders
Vomiting
|
6.2%
13/209
|
9.7%
21/216
|
|
General disorders
Asthenia
|
8.6%
18/209
|
15.3%
33/216
|
|
General disorders
Fatigue
|
4.8%
10/209
|
5.6%
12/216
|
|
General disorders
Pain
|
4.8%
10/209
|
6.9%
15/216
|
|
General disorders
Pyrexia
|
10.5%
22/209
|
13.0%
28/216
|
|
Investigations
Gamma-glutamyltransferase increased
|
3.8%
8/209
|
5.6%
12/216
|
|
Metabolism and nutrition disorders
Anorexia
|
2.4%
5/209
|
5.6%
12/216
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
4.3%
9/209
|
6.0%
13/216
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.3%
7/209
|
6.0%
13/216
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
26.8%
56/209
|
29.6%
64/216
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
3.8%
8/209
|
5.6%
12/216
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
32.1%
67/209
|
31.5%
68/216
|
|
Nervous system disorders
Headache
|
6.7%
14/209
|
6.9%
15/216
|
|
Nervous system disorders
Paraesthesia
|
5.3%
11/209
|
3.7%
8/216
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.7%
14/209
|
5.6%
12/216
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
4.3%
9/209
|
6.0%
13/216
|
|
Skin and subcutaneous tissue disorders
Rash
|
1.4%
3/209
|
5.6%
12/216
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
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.
- Publication restrictions are in place
Restriction type: OTHER