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Safety and Efficacy of Zoledronic Acid in Patients With Breast Cancer With Metastatic Bone Lesions

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00375427
First received: September 12, 2006
Last updated: April 9, 2012
Last verified: July 2011
History of Changes
Results First Received: February 28, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Breast Cancer With Bone Metastasis
Intervention: Drug: Zoledronic acid

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Total enrollment was 430; five participants were screened but not treated.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
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.

Participant Flow:   Overall Study
    Zoledronic Acid Every 3 Months     Zoledronic Acid Every 4 Weeks  
STARTED     209 [1]   216  
COMPLETED     149     142  
NOT COMPLETED     60     74  
Adverse Event                 21                 27  
Abnormal test procedure result(s)                 0                 1  
Abnormal laboratory value(s)                 1                 2  
Unsatisfactory therapeutic effect                 4                 4  
Patient no longer requires study drug                 3                 7  
Protocol Violation                 10                 8  
Withdrawal by Subject                 9                 13  
Lost to Follow-up                 1                 1  
Administrative reasons                 0                 1  
Death                 11                 10  
[1] Total enrollment was 430 but five patients were screened but not treated.



  Baseline Characteristics
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Reporting Groups
  Description
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.
Total Total of all reporting groups

Baseline Measures
    Zoledronic Acid Every 3 Months     Zoledronic Acid Every 4 Weeks     Total  
Number of Participants  
[units: participants]
 		  209     216     425  
Age  
[units: years]
Mean ± Standard Deviation 		  60.4  ± 11.9     59.8  ± 11.8     60.1  ± 11.9  
Gender  
[units: participants]
 		     
Female     209     216     425  
Male     0     0     0  



  Outcome Measures
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1.  Primary:   Annual Overall Skeletal Morbidity Rate (SMR)   [ Time Frame: 12 months ]
  Show Outcome Measure 1

2.  Secondary:   Percentage of Participants Experiencing Skeletal Related Event(s) (SREs)   [ Time Frame: 12 month ]
  Show Outcome Measure 2

3.  Secondary:   Annual Incidence of Any Skeletal Related Events (SREs)   [ Time Frame: 12 months ]
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4.  Secondary:   Median Time to First Skeletal Related Event(s) (SRE)   [ Time Frame: 12 month ]
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5.  Secondary:   Percentage of Participants Skeletal Related Event (SRE) Free   [ Time Frame: 12 months ]
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6.  Secondary:   Composite Bone Pain Score According to the Brief Pain Inventory (BPI) Questionnaire   [ Time Frame: At Baseline, Month 3, Month 6, Month 9 and Month 12 ]
  Show Outcome Measure 6

7.  Secondary:   Evaluation of Pain According to Verbal Rating Scale (VRS) Based on Median Score Value   [ Time Frame: At Baseline, Month 3, Month 6, Month 9 and Month 12 ]
  Show Outcome Measure 7

8.  Secondary:   Use Of Analgesic Medications According to the Analgesic Score Scale   [ Time Frame: At Baseline, Month 3, Month 6, Month 9 and Month 12 ]
  Show Outcome Measure 8

9.  Secondary:   Assessment of the Eastern Cooperative Oncology Group (ECOG) Performance Score   [ Time Frame: At Baseline, Month 3, Month 6, Month 9 and Month 12 ]
  Show Outcome Measure 9


  Serious Adverse Events
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  Other Adverse Events
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Time Frame No text entered.
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

Reporting Groups
  Description
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

Other Adverse Events
    Zoledronic Acid Every 3 Months     Zoledronic Acid Every 4 Weeks  
Total, other (not including serious) adverse events      
# participants affected / at risk     133/209     161/216  
Blood and lymphatic system disorders      
Anaemia † 1    
# participants affected / at risk     13/209 (6.22%)     21/216 (9.72%)  
Neutropenia † 1    
# participants affected / at risk     11/209 (5.26%)     18/216 (8.33%)  
Ear and labyrinth disorders      
Vertigo † 1    
# participants affected / at risk     2/209 (0.96%)     11/216 (5.09%)  
Gastrointestinal disorders      
Abdominal pain † 1    
# participants affected / at risk     12/209 (5.74%)     15/216 (6.94%)  
Abdominal pain upper † 1    
# participants affected / at risk     16/209 (7.66%)     20/216 (9.26%)  
Constipation † 1    
# participants affected / at risk     12/209 (5.74%)     15/216 (6.94%)  
Diarrhoea † 1    
# participants affected / at risk     12/209 (5.74%)     17/216 (7.87%)  
Nausea † 1    
# participants affected / at risk     24/209 (11.48%)     32/216 (14.81%)  
Vomiting † 1    
# participants affected / at risk     13/209 (6.22%)     21/216 (9.72%)  
General disorders      
Asthenia † 1    
# participants affected / at risk     18/209 (8.61%)     33/216 (15.28%)  
Fatigue † 1    
# participants affected / at risk     10/209 (4.78%)     12/216 (5.56%)  
Pain † 1    
# participants affected / at risk     10/209 (4.78%)     15/216 (6.94%)  
Pyrexia † 1    
# participants affected / at risk     22/209 (10.53%)     28/216 (12.96%)  
Investigations      
Gamma-glutamyltransferase increased † 1    
# participants affected / at risk     8/209 (3.83%)     12/216 (5.56%)  
Metabolism and nutrition disorders      
Anorexia † 1    
# participants affected / at risk     5/209 (2.39%)     12/216 (5.56%)  
Musculoskeletal and connective tissue disorders      
Arthralgia † 1    
# participants affected / at risk     9/209 (4.31%)     13/216 (6.02%)  
Back pain † 1    
# participants affected / at risk     7/209 (3.35%)     13/216 (6.02%)  
Bone pain † 1    
# participants affected / at risk     56/209 (26.79%)     64/216 (29.63%)  
Pain in extremity † 1    
# participants affected / at risk     8/209 (3.83%)     12/216 (5.56%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Malignant neoplasm progression † 1    
# participants affected / at risk     67/209 (32.06%)     68/216 (31.48%)  
Nervous system disorders      
Headache † 1    
# participants affected / at risk     14/209 (6.70%)     15/216 (6.94%)  
Paraesthesia † 1    
# participants affected / at risk     11/209 (5.26%)     8/216 (3.70%)  
Respiratory, thoracic and mediastinal disorders      
Cough † 1    
# participants affected / at risk     14/209 (6.70%)     12/216 (5.56%)  
Dyspnoea † 1    
# participants affected / at risk     9/209 (4.31%)     13/216 (6.02%)  
Skin and subcutaneous tissue disorders      
Rash † 1    
# participants affected / at risk     3/209 (1.44%)     12/216 (5.56%)  
† Events were collected by systematic assessment
1 Term from vocabulary, MedDRA



  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300


No publications provided


Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00375427     History of Changes
Other Study ID Numbers: CZOL446EIT14
Study First Received: September 12, 2006
Results First Received: February 28, 2011
Last Updated: April 9, 2012
Health Authority: Italy: Ethics Committee