Breast Cancer With Bone MetastasisPhase 3NCT00375427
Safety and Efficacy of Zoledronic Acid in Patients With Breast Cancer With Metastatic Bone Lesions
A Phase 3 study testing Zoledronic acid in people with Breast Cancer With Bone Metastasis, run by Novartis Pharmaceuticals at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer With Bone Metastasis
- What is being tested?
- Zoledronic acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 430 participants
- Where
- 1 siteItaly
- Study dates
- Feb 2006to Feb 2010
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Prospective, Randomized, Multi-center Comparative 2-arm Trial of Efficacy and Safety of Zoledronic Acid (Every 3-months vs. Every 4 Weeks) Beyond Approximately 1 Year of Treatment With Zoledronic Acid in Patients With Bone Lesions From Breast Cancer
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.
- Conditions
- Breast Cancer With Bone Metastasis
- Being tested
- Zoledronic acid
- Keywords
- Breast cancer, Zoledronic acid, Skeletal related events (SRE)
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zoledronic acidDrug
Also called ZOL446, Zometa®
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.
| Study group | Role | What they receive |
|---|---|---|
| Every 3 months | Experimental | 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. Receives: Drug: Zoledronic acid |
| Every 4 weeks | Experimental | 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. Receives: Drug: Zoledronic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Annual Overall Skeletal Morbidity Rate (SMR)
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.
Measured: 12 months
Secondary outcomes (8)
Percentage of Participants Experiencing Skeletal Related Event(s) (SREs)
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.
Measured: 12 month
Annual Incidence of Any Skeletal Related Events (SREs)
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.
Measured: 12 months
Median Time to First Skeletal Related Event(s) (SRE)
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.
Measured: 12 month
Percentage of Participants Skeletal Related Event (SRE) Free
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.
Measured: 12 months
Composite Bone Pain Score According to the Brief Pain Inventory (BPI) Questionnaire
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
Measured: At Baseline, Month 3, Month 6, Month 9 and Month 12
Evaluation of Pain According to Verbal Rating Scale (VRS) Based on Median Score Value
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.
Measured: At Baseline, Month 3, Month 6, Month 9 and Month 12
Use Of Analgesic Medications According to the Analgesic Score Scale
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
Measured: At Baseline, Month 3, Month 6, Month 9 and Month 12
Assessment of the Eastern Cooperative Oncology Group (ECOG) Performance Score
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
Measured: At Baseline, Month 3, Month 6, Month 9 and Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2006 (estimated)
- Study startFeb 2006
- Primary completionFeb 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast Cancer With Bone MetastasisStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 430 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00375427
- Sponsor's protocol ID
- CZOL446EIT14
- Status last verified
- Jul 2011
- First submitted
- 12 Sep 2006
- Last updated
- 11 Apr 2012
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized, Multi-center Comparative 2-arm Trial of Efficacy and Safety of Zoledronic Acid (Every 3-months vs. Every 4 Weeks) Beyond Approximately 1 Year of Treatment With Zoledronic Acid in Patients With Bone Lesions From Breast Cancer
- ClinicalTrials.gov ID
- NCT00375427
- Acronym / sponsor ID
- CZOL446EIT14
- Conditions
- Breast Cancer With Bone Metastasis
- Keywords
- Breast cancer, Zoledronic acid, Skeletal related events (SRE)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 430 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Feb 2006
- Primary completion
- Feb 2010 (actual)
- First posted
- 13 Sep 2006 (estimated)
- Results
- Posted 4 Aug 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Every 3 months | Experimental | Drug: Zoledronic acidZoledronic 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. |
| Every 4 weeks | Experimental | Drug: Zoledronic acidZoledronic 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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 .
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zoledronic acidAlso: ZOL446, Zometa®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. | Drug | Every 3 months, Every 4 weeks |
Primary outcome
Annual Overall Skeletal Morbidity Rate (SMR)
Time frame: 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.
8 secondary outcomes
Percentage of Participants Experiencing Skeletal Related Event(s) (SREs)
Time frame: 12 month
Annual Incidence of Any Skeletal Related Events (SREs)
Time frame: 12 months
Median Time to First Skeletal Related Event(s) (SRE)
Time frame: 12 month
Percentage of Participants Skeletal Related Event (SRE) Free
Time frame: 12 months
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
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
Use Of Analgesic Medications According to the Analgesic Score Scale
Time frame: At Baseline, Month 3, Month 6, Month 9 and Month 12
Assessment of the Eastern Cooperative Oncology Group (ECOG) Performance Score
Time frame: At Baseline, Month 3, Month 6, Month 9 and Month 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Zoledronic acid in people with Breast Cancer With Bone Metastasis, run by Novartis Pharmaceuticals at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Aug 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Annual Overall Skeletal Morbidity Rate (SMR) (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2012.