Safety and Efficacy of Zoledronic Acid in Patients With Breast Cancer With Metastatic Bone Lesions
Study Details
Study Description
Brief Summary
The objective of this study is to assess the clinical benefit of two different dosing schedules of zoledronic acid in patients with metastatic bone lesions from breast cancer who have already been treated with zoledronic acid for about one year.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Every 3 months Zoledronic acid as a 15-minute (at least) intravenous (i.v.) infusion every three months. The dose of study drug will be the same administered before the study entry, that is 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized patients will receive a maximum of 4 infusions in this group. |
Drug: Zoledronic acid
Zoledronic acid as a 15-minute (at least) intravenous (i.v.) infusion. The dose of study drug will be the same administered before the study entry, that is 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg.
Other Names:
|
| Experimental: Every 4 weeks Zoledronic acid as a 15-minute (at least) intravenous (i.v.) infusion every 4 weeks. The dose of study drug will be the same administered before the study entry, that is 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Patients randomized to this group will receive up to 12 infusions. |
Drug: Zoledronic acid
Zoledronic acid as a 15-minute (at least) intravenous (i.v.) infusion. The dose of study drug will be the same administered before the study entry, that is 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Annual Overall Skeletal Morbidity Rate (SMR) [12 months]
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.
Secondary Outcome Measures
- Percentage of Participants Experiencing Skeletal Related Event(s) (SREs) [12 month]
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.
- Annual Incidence of Any Skeletal Related Events (SREs) [12 months]
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.
- Median Time to First Skeletal Related Event(s) (SRE) [12 month]
Median 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.
- Percentage of Participants Skeletal Related Event (SRE) Free [12 months]
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.
- Composite Bone Pain Score According to the Brief Pain Inventory (BPI) Questionnaire [At Baseline, Month 3, Month 6, Month 9 and Month 12]
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
- Evaluation of Pain According to Verbal Rating Scale (VRS) Based on Median Score Value [At Baseline, Month 3, Month 6, Month 9 and Month 12]
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.
- Use Of Analgesic Medications According to the Analgesic Score Scale [At Baseline, Month 3, Month 6, Month 9 and Month 12]
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 = Minor analgesics (aspirin, NSAID, acetaminophen, propoxyphene, etc.) = Tranquilisers, antidepressants, muscle relaxants, and steroids = Mild narcotics (oxycodone, meperidine, codeine, etc.) = 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
- Assessment of the Eastern Cooperative Oncology Group (ECOG) Performance Score [At Baseline, Month 3, Month 6, Month 9 and Month 12]
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
Eligibility Criteria
Criteria
Inclusion criteria:
-
Female patients ≥ 18 years of age.
-
Written informed consent given.
-
Histologically confirmed Stage IV breast cancer with at least one bone metastasis radiologically confirmed.
-
Previous treatment with zoledronic acid every 3-4 weeks, for 9-12 infusions over no more than 15 months.
-
Eastern Cooperative Oncology Group (ECOG) performance status ≤2 .
-
Life expectancy ≥ 1 year.
Exclusion criteria:
-
More than 3 months since last infusion of Zoledronic Acid (Zometa®).
-
Treatments with other bisphosphonate than Zoledronic Acid (Zometa®) at any time prior to study entry.
-
Serum creatinine > 3 mg/dL (265 μmol/L) or calculated (Cockcroft-Gault formula) creatinine clearance (CLCr) < 30 mL/min CrCl = ({[140-age (years)] x weight(kg)}/ [72 x serum creatinine (mg/dL)])x 0.85
-
Corrected (adjusted for serum albumin) serum calcium < 8 mg/dl (2 mmol/L) or > 12 mg/dL ( 3.0 mmol/L).
-
Current active dental problem including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a recurrent or prior diagnosis of osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures.
-
Recent (within 6 weeks) or planned dental or jaw surgery (e.g. extraction, implants).
-
Pregnant patients (with a positive pregnancy test prior to study entry) or lactating patients. Women of childbearing potential not using effective methods of birth control (e.g. abstinence, oral contraceptives or implants, IUD, vaginal diaphragm or sponge, or condom with spermicide).
-
History of non-compliance to medical regimens or potential unreliable behavior.
-
Known sensitivity to study drug(s) or class of study drug(s).
-
Patients with severe medical condition(s) that in the view of the investigator prohibits participation in the study
-
Use of any other investigational agent in the last 30 days.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Forlì | Italy |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CZOL446EIT14
Study Results
Participant Flow
| Recruitment Details | Total enrollment was 430; five participants were screened but not treated. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Zoledronic Acid Every 3 Months | Zoledronic Acid Every 4 Weeks |
|---|---|---|
| Arm/Group Description | 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 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. |
| Period Title: Overall Study | ||
| STARTED | 209 | 216 |
| COMPLETED | 149 | 142 |
| NOT COMPLETED | 60 | 74 |
Baseline Characteristics
| Arm/Group Title | Zoledronic Acid Every 3 Months | Zoledronic Acid Every 4 Weeks | Total |
|---|---|---|---|
| Arm/Group Description | 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 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 of all reporting groups |
| Overall Participants | 209 | 216 | 425 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
60.4
(11.9)
|
59.8
(11.8)
|
60.1
(11.9)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
209
100%
|
216
100%
|
425
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Annual Overall Skeletal Morbidity Rate (SMR) |
|---|---|
| Description | 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. |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population will include all randomized patients. |
| Arm/Group Title | Zoledronic Acid Every 3 Months | Zoledronic Acid Every 4 Weeks |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 209 | 216 |
| Mean (Standard Deviation) [Number of Skeletal Events per Year] |
0.26
(0.81)
|
0.22
(0.57)
|
| Title | Percentage of Participants Experiencing Skeletal Related Event(s) (SREs) |
|---|---|
| Description | 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. |
| Time Frame | 12 month |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population will include all randomized patients. |
| Arm/Group Title | Zoledronic Acid Every 3 Months | Zoledronic Acid Every 4 Weeks |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 209 | 216 |
| Patient with any SRE |
14.83
7.1%
|
15.28
7.1%
|
| Vertebral pathological fracture |
1.44
0.7%
|
1.85
0.9%
|
| Non vertebral pathological fracture |
3.35
1.6%
|
2.31
1.1%
|
| Spinal cord compression |
0.96
0.5%
|
0.46
0.2%
|
| Radiation to bone |
10.53
5%
|
11.11
5.1%
|
| Surgery to bone |
0.96
0.5%
|
0.46
0.2%
|
| Hypercalcemia of malignancy |
0.48
0.2%
|
1.85
0.9%
|
| Title | Annual Incidence of Any Skeletal Related Events (SREs) |
|---|---|
| Description | 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. |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population will include all randomized patients. |
| Arm/Group Title | Zoledronic Acid Every 3 Months | Zoledronic Acid Every 4 Weeks |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 209 | 216 |
| Vertebral pathological fracture rate |
0.02
(0.19)
|
0.02
(0.15)
|
| Non-vertebral pathological fracture rate |
0.08
(0.58)
|
0.03
(0.20)
|
| Spinal cord compression rate |
0.01
(0.10)
|
0.00
(0.07)
|
| Radiation to bone rate |
0.17
(0.67)
|
0.14
(0.43)
|
| Surgery to bone rate |
0.02
(0.21)
|
0.00
(0.07)
|
| Hypercalcemia of malignancy rate |
0.01
(0.08)
|
0.02
(0.16)
|
| Title | Median Time to First Skeletal Related Event(s) (SRE) |
|---|---|
| Description | Median 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. |
| Time Frame | 12 month |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Zoledronic Acid Every 3 Months | Zoledronic Acid Every 4 Weeks |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 209 | 216 |
| Number [Day] |
NA
|
NA
|
| Title | Percentage of Participants Skeletal Related Event (SRE) Free |
|---|---|
| Description | 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. |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population will include all randomized patients. |
| Arm/Group Title | Zoledronic Acid Every 3 Months | Zoledronic Acid Every 4 Weeks |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 209 | 216 |
| At Month 1 |
99
47.4%
|
98
45.4%
|
| At Month 2 |
98
46.9%
|
98
45.4%
|
| At Month 3 |
96
45.9%
|
97
44.9%
|
| At Month 4 |
94
45%
|
95
44%
|
| At Month 5 |
94
45%
|
93
43.1%
|
| At Month 6 |
93
44.5%
|
92
42.6%
|
| At Month 7 |
88
42.1%
|
90
41.7%
|
| At Month 8 |
86
41.1%
|
88
40.7%
|
| At Month 9 |
85
40.7%
|
85
39.4%
|
| At Month 10 |
84
40.2%
|
83
38.4%
|
| At Month 11 |
83
39.7%
|
83
38.4%
|
| At Month 12 |
78
37.3%
|
82
38%
|
| Title | Composite Bone Pain Score According to the Brief Pain Inventory (BPI) Questionnaire |
|---|---|
| Description | 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 |
| Time Frame | At Baseline, Month 3, Month 6, Month 9 and Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population will include all randomized patients. All ITT patients with BPI questionnaire filled up at baseline were included. |
| Arm/Group Title | Zoledronic Acid Every 3 Months | Zoledronic Acid Every 4 Weeks |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 186 | 185 |
| Baseline (N= 186, 185) |
2.0
(1.8)
|
2.1
(1.9)
|
| Month 3 (N= 156, 163) |
2.3
(2.0)
|
2.2
(1.9)
|
| Month 6 (N= 143, 160) |
2.3
(2.2)
|
1.9
(1.8)
|
| Month 9 (N= 131, 130) |
2.3
(2.2)
|
2.1
(2.0)
|
| Month 12 (N= 135, 124) |
2.4
(2.3)
|
2.1
(2.0)
|
| Title | Evaluation of Pain According to Verbal Rating Scale (VRS) Based on Median Score Value |
|---|---|
| Description | 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. |
| Time Frame | At Baseline, Month 3, Month 6, Month 9 and Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population will include all randomized patients. |
| Arm/Group Title | Zoledronic Acid Every 3 Months | Zoledronic Acid Every 4 Weeks |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 209 | 216 |
| At Rest: Baseline |
1
|
1
|
| At Rest: Month 3 |
2
|
2
|
| At Rest: Month 6 |
2
|
1
|
| At Rest: Month 9 |
1
|
1
|
| At Rest: Month 12 |
2
|
1
|
| At Movement : Baseline |
2
|
2
|
| At Movement : Month 3 |
2
|
2
|
| At Movement : Month 6 |
2
|
2
|
| At Movement : Month 9 |
2
|
2
|
| At Movement : Month 12 |
2.5
|
2
|
| Title | Use Of Analgesic Medications According to the Analgesic Score Scale |
|---|---|
| Description | 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 = Minor analgesics (aspirin, NSAID, acetaminophen, propoxyphene, etc.) = Tranquilisers, antidepressants, muscle relaxants, and steroids = Mild narcotics (oxycodone, meperidine, codeine, etc.) = 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 |
| Time Frame | At Baseline, Month 3, Month 6, Month 9 and Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population will include all randomized patients. |
| Arm/Group Title | Zoledronic Acid Every 3 Months | Zoledronic Acid Every 4 Weeks |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 209 | 216 |
| Baseline |
0
|
0
|
| Month 3 |
0
|
0
|
| Month 6 |
0
|
0
|
| Month 9 |
0
|
0
|
| Month 12 |
0
|
0
|
| Title | Assessment of the Eastern Cooperative Oncology Group (ECOG) Performance Score |
|---|---|
| Description | 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 |
| Time Frame | At Baseline, Month 3, Month 6, Month 9 and Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population will include all randomized patients. |
| Arm/Group Title | Zoledronic Acid Every 3 Months | Zoledronic Acid Every 4 Weeks |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 209 | 216 |
| Baseline |
0
|
0
|
| Month 3 |
0
|
0
|
| Month 6 |
0
|
0
|
| Month 9 |
0
|
0
|
| Month 12 |
0
|
0
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Zoledronic Acid Every 3 Months | Zoledronic Acid Every 4 Weeks | ||
| Arm/Group Description | 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 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 | ||
All Cause Mortality |
||||
| Zoledronic Acid Every 3 Months | Zoledronic Acid Every 4 Weeks | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Zoledronic Acid Every 3 Months | Zoledronic Acid Every 4 Weeks | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 21/209 (10%) | 29/216 (13.4%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 0/209 (0%) | 2/216 (0.9%) | ||
| Febrile neutropenia | 0/209 (0%) | 2/216 (0.9%) | ||
| Thrombocytopenia | 0/209 (0%) | 2/216 (0.9%) | ||
| Cardiac disorders | ||||
| Acute myocardial infarction | 0/209 (0%) | 1/216 (0.5%) | ||
| Cardiac failure | 0/209 (0%) | 1/216 (0.5%) | ||
| Eye disorders | ||||
| Diplopia | 0/209 (0%) | 1/216 (0.5%) | ||
| Gastrointestinal disorders | ||||
| Gastric haemorrhage | 0/209 (0%) | 1/216 (0.5%) | ||
| Nausea | 0/209 (0%) | 1/216 (0.5%) | ||
| Oral pain | 0/209 (0%) | 2/216 (0.9%) | ||
| Vomiting | 1/209 (0.5%) | 2/216 (0.9%) | ||
| General disorders | ||||
| Mucosal inflammation | 0/209 (0%) | 1/216 (0.5%) | ||
| Pain | 1/209 (0.5%) | 0/216 (0%) | ||
| Hepatobiliary disorders | ||||
| Jaundice | 0/209 (0%) | 1/216 (0.5%) | ||
| Infections and infestations | ||||
| Acute sinusitis | 1/209 (0.5%) | 0/216 (0%) | ||
| Pneumonia | 0/209 (0%) | 1/216 (0.5%) | ||
| Sepsis | 0/209 (0%) | 1/216 (0.5%) | ||
| Skin infection | 0/209 (0%) | 1/216 (0.5%) | ||
| Injury, poisoning and procedural complications | ||||
| Femur fracture | 2/209 (1%) | 1/216 (0.5%) | ||
| Humerus fracture | 0/209 (0%) | 1/216 (0.5%) | ||
| Metabolism and nutrition disorders | ||||
| Cachexia | 1/209 (0.5%) | 1/216 (0.5%) | ||
| Hypercalcaemia | 0/209 (0%) | 1/216 (0.5%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Bone pain | 1/209 (0.5%) | 2/216 (0.9%) | ||
| Jaw disorder | 0/209 (0%) | 1/216 (0.5%) | ||
| Musculoskeletal chest pain | 1/209 (0.5%) | 0/216 (0%) | ||
| Osteitis | 0/209 (0%) | 1/216 (0.5%) | ||
| Osteonecrosis | 4/209 (1.9%) | 3/216 (1.4%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Malignant neoplasm progression | 2/209 (1%) | 1/216 (0.5%) | ||
| Metastases to central nervous system | 1/209 (0.5%) | 0/216 (0%) | ||
| Nervous system disorders | ||||
| Cranial nerve paralysis | 0/209 (0%) | 1/216 (0.5%) | ||
| Epilepsy | 1/209 (0.5%) | 0/216 (0%) | ||
| Ischaemic cerebral infarction | 0/209 (0%) | 1/216 (0.5%) | ||
| Paraparesis | 0/209 (0%) | 1/216 (0.5%) | ||
| Psychiatric disorders | ||||
| Depression | 1/209 (0.5%) | 0/216 (0%) | ||
| Sopor | 0/209 (0%) | 1/216 (0.5%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 2/209 (1%) | 2/216 (0.9%) | ||
| Dyspnoea exertional | 0/209 (0%) | 1/216 (0.5%) | ||
| Haemoptysis | 0/209 (0%) | 1/216 (0.5%) | ||
| Pleural effusion | 0/209 (0%) | 1/216 (0.5%) | ||
| Pulmonary embolism | 1/209 (0.5%) | 0/216 (0%) | ||
| Surgical and medical procedures | ||||
| Breast operation | 1/209 (0.5%) | 0/216 (0%) | ||
| Laparoscopic surgery | 0/209 (0%) | 1/216 (0.5%) | ||
| Vascular disorders | ||||
| Deep vein thrombosis | 1/209 (0.5%) | 1/216 (0.5%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Zoledronic Acid Every 3 Months | Zoledronic Acid Every 4 Weeks | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 133/209 (63.6%) | 161/216 (74.5%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 13/209 (6.2%) | 21/216 (9.7%) | ||
| Neutropenia | 11/209 (5.3%) | 18/216 (8.3%) | ||
| Ear and labyrinth disorders | ||||
| Vertigo | 2/209 (1%) | 11/216 (5.1%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 12/209 (5.7%) | 15/216 (6.9%) | ||
| Abdominal pain upper | 16/209 (7.7%) | 20/216 (9.3%) | ||
| Constipation | 12/209 (5.7%) | 15/216 (6.9%) | ||
| Diarrhoea | 12/209 (5.7%) | 17/216 (7.9%) | ||
| Nausea | 24/209 (11.5%) | 32/216 (14.8%) | ||
| Vomiting | 13/209 (6.2%) | 21/216 (9.7%) | ||
| General disorders | ||||
| Asthenia | 18/209 (8.6%) | 33/216 (15.3%) | ||
| Fatigue | 10/209 (4.8%) | 12/216 (5.6%) | ||
| Pain | 10/209 (4.8%) | 15/216 (6.9%) | ||
| Pyrexia | 22/209 (10.5%) | 28/216 (13%) | ||
| Investigations | ||||
| Gamma-glutamyltransferase increased | 8/209 (3.8%) | 12/216 (5.6%) | ||
| Metabolism and nutrition disorders | ||||
| Anorexia | 5/209 (2.4%) | 12/216 (5.6%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 9/209 (4.3%) | 13/216 (6%) | ||
| Back pain | 7/209 (3.3%) | 13/216 (6%) | ||
| Bone pain | 56/209 (26.8%) | 64/216 (29.6%) | ||
| Pain in extremity | 8/209 (3.8%) | 12/216 (5.6%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Malignant neoplasm progression | 67/209 (32.1%) | 68/216 (31.5%) | ||
| Nervous system disorders | ||||
| Headache | 14/209 (6.7%) | 15/216 (6.9%) | ||
| Paraesthesia | 11/209 (5.3%) | 8/216 (3.7%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 14/209 (6.7%) | 12/216 (5.6%) | ||
| Dyspnoea | 9/209 (4.3%) | 13/216 (6%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash | 3/209 (1.4%) | 12/216 (5.6%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
- CZOL446EIT14