Breast CancerPhase 3CTIBLNCT00712985
Single Dosing of Zoledronic Acid in Cancer Therapy Induced Bone Loss (CTIBL)
A Phase 3 study testing Zometa in people with Breast Cancer, run by Milton S. Hershey Medical Center at 1 site in United States.
Trial summary
The purpose of this research is to establish if a once a year dose of Zoledronic Acid is sufficient to suppress and maintain urine and serum bone density markers (NTx) and serum CTx within normal range at 12 months post-dosing in postmenopausal early breast cancer patients receiving additional treatment with… Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Zometa
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2005to Mar 2011
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Postmenopausal women with Stage I, II or IIIa breast cancer being treated with a non-steroidal Aromatase Inhibitor (AI) .Negative bone scan (no bone metastases).
- Calculated creatinine clearance > 40 ml/min
- Documented T score of less than or equal to -1.5 on Dual Energy X-ray Absorptiionmetry (DXA) scan at the lumbar spine or femoral neck within 3 months prior to screening.
- Urine NTx > 50 nano moles(nM)based on second morning void.
- Signed informed consent.
- Ambulatory patients at least 18 years of age.
- Eastern Cooperative Oncology Group (ECOG)0-2.
- Ability to comply with trial requirements.
Who cannot join
- Bone Metastases.
- Any woman of child bearing potential.
- Patients with fractures occurring within three months prior to randomization. - Greater than a 2+ protein on urine dipstick without evidence of contamination or bacteriuria (may be repeated one time, at least a day apart).
- Calculated creatinine clearance less than 30 mL/min at screening.
- Serum calcium > 2.75 mmol/L (11.0 mg/dL) or < 2.00 mmol/L (8.0 mg/dL).
- Liver Function tests (LFT)> 2.0 x upper limit of normal (ULN).
Show all 23Show fewer
- Serum alkaline phosphatase > 1.5 x ULN. History of hypersensitivity to bisphosphonates.
- Evidence of vitamin D deficiency (serum 25-(OH) D of less than 15 ng/ml).
- History of uveitis or iritis, except when secondary to trauma, and must have resolved > 2 years prior to entry.
- A history of invasive malignancy of any organ system, treated or untreated, within the past 12 months prior to screening; excluding, basal cell or squamous cell carcinoma of the skin, colonic polyps with non-invasive malignancy which have been removed, Ductal Carcinoma in-situ (DCIS) that has been surgically removed, and Carcinoma in-situ (CIS) of the uterine cervix that has been surgically removed.
- Previous major solid organ transplant recipient or on a transplant waiting list.
- Treatment with any investigational drug within 30 days prior to randomization.
- History of hyperparathyroidism, hypoparathyroidism, Osteogenesis imperfecta, Paget's disease or any metabolic bone disease other than osteoporosis.
- Any medical condition which would interfere with the action of the study drug or limit life expectancy to less than 6 months.
- Any medical or psychiatric condition which, in the opinion of the investigator, would preclude the participant from adhering to the protocol or completing the trial.
- Prior treatment with IV bisphosphonates within the last 2 years.
- Previous use of oral bisphosphonates within the past 2 years (unless used for less than 8 weeks*). *NOTE: If used less than 8 weeks, the washout period is 6 months.
- Treatment with raloxifene, calcitonin, tibolone or hormone replacement therapy. The washout period for these medications is 6 months prior to randomization.
- Any treatment with strontium ranelate, samarium, sodium fluoride or parathyroid hormone.
- Use of systemic high dose corticosteroids at an average dose of > 7.5 mg per day of oral prednisone or equivalent for a period of three months or more prior to screening.
- Known hypersensitivity to zoledronic acid or other bisphosphonates.
- Current active dental problems including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
About this study
The purpose of this research is to establish if a once a year dose of Zoledronic Acid is sufficient to suppress and maintain urine and serum bone density markers (NTx) and serum CTx within normal range at 12 months post-dosing in postmenopausal early breast cancer patients receiving additional treatment with non-steroidal aromatase inhibitors.
Read the detailed description
Bone metastases are frequently one of the first signs of disseminated disease in cancer patients. Skeletal complications due to metastatic disease include (severe) bone pain, spinal cord compromise, pathological fractures, and hypercalcemia.
Zoledronic acid is a member of a class of compounds known as bisphosphonates. Bisphosphonates are effective inhibitors of osteoclastic bone resorption and have demonstrated therapeutic efficacy in the treatments of hypercalcemia of malignancy, lytic bone disease associated with multiple myeloma, and mixed lytic and blastic bone metastases associated with breast cancer. The precise mechanism by which bisphosphonates inhibit osteoclast function is not fully understood, but may include a direct toxic effect on mature osteoclasts, an inhibition of osteoclast production from precursor cells, and an impairment of osteoclast chemotaxis to sites of active bone resorption. Osteoclasts are specialized bone cells which erode mineralized bone by secreting acids and lysosomal enzymes. In normal bone remodeling, osteoclastic bone resorption is coupled to and is in equilibrium with osteoblastic bone formation. The lytic bone destruction associated with malignant bone metastases develops because tumor cells synthesize and release soluble factors that stimulate osteoclasts to resorb bone. The osteoclastic activating factors released by tumor cells include parathyroid hormone-related peptide (PTHrP), growth factors, and cytokines. The malignant activation of osteoclasts results in a disruption of normal bone remodeling wherein the equilibrium between bone resorption and bone formation is shifted toward increased bone resorption. This relative increase in osteoclastic bone resorption results in a net loss of bone. Thus, the predominant role of the osteoclast in the pathogenesis of bone destruction and the inhibitory effects of bisphosphonates on osteoclast function have formed the rationale for the use of bisphosphonates in the treatment of osteolytic bone metastases. The common role, regardless of tumor type, of the osteoclast as the mediator of bone destruction in metastatic skeletal disease is indicated by the inhibitory effects of bisphosphonates on tumor-induced osteolysis in animal models utilizing various malignant cell lines and the effectiveness of bisphosphonates in the therapy of tumor-induced hypercalcemia arising from any type of cancer. Moreover, recent studies have specifically shown that therapy with the bisphosphonate pamidronate (Aredia) combined with antineoplastic therapy significantly reduces the proportion of patients having skeletal complications due to the lytic bone disease associated with multiple myeloma and breast cancer compared to antineoplastic therapy alone.
- Conditions
- Breast Cancer
- Being tested
- Zometa
- Keywords
- Breast cancer, aromatase inhibitors
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZometaDrug
Also called Zoledronic Acid
Zometa (Zoledronic Acid) 5 mg IV over 15 minutes in a one time dose
| Study group | Role | What they receive |
|---|---|---|
| Zometa (Zoledronic Acid) X 1 dose | Experimental | Zometa (Zoledronic Acid) 5 mg IV X 1 dose Receives: Drug: Zometa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Urine and Serum NTx and Serum CTx Within Normal Range at 12 Months
17 women with early breast cancer receiving adjuvant Aromatase Inhibitor (AI) therapy were treated with a single 5 mg IV dose of zoledronic acid. Urine and serum NTx and serum CTx were measured at baseline and month 12.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2008 (estimated)
- Study startSep 2005
- Primary completionMar 2011
- Study completionMar 2011
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.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Milton S. Hershey Medical CenterThe 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
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Principal investigator, Allan Lipton, Milton S. Hershey Medical Center
- Investigators
- Allan Lipton, MD, Principal investigator, Milton S. Hershey Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00712985
- Sponsor's protocol ID
- CZOL446H US113
- Acronym
- CTIBL
- Status last verified
- Mar 2014
- First submitted
- 9 Jul 2008
- Last updated
- 24 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Baum M, Budzar AU, Cuzick J, Forbes J, Houghton JH, Klijn JG, Sahmoud T; ATAC Trialists' Group. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet. 2002 Jun 22;359(9324):2131-9. doi: 10.1016/s0140-6736(02)09088-8.
PubMed 12090977Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Therasse P, Palmer MJ, Pater JL. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med. 2003 Nov 6;349(19):1793-802. doi: 10.1056/NEJMoa032312. Epub 2003 Oct 9.
PubMed 14551341Coombes RC, Hall E, Gibson LJ, Paridaens R, Jassem J, Delozier T, Jones SE, Alvarez I, Bertelli G, Ortmann O, Coates AS, Bajetta E, Dodwell D, Coleman RE, Fallowfield LJ, Mickiewicz E, Andersen J, Lonning PE, Cocconi G, Stewart A, Stuart N, Snowdon CF, Carpentieri M, Massimini G, Bliss JM, van de Velde C; Intergroup Exemestane Study. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004 Mar 11;350(11):1081-92. doi: 10.1056/NEJMoa040331.
PubMed 15014181BIG 1-98 Collaborative Group. Letrozole versus tamoxifen as adjuvant endocrine therapy for postmenopausal women with receptor-positive breast cancer. BIG 1-98: a prospective randomized double-blind phase III study. Breast. 2005;14:Suppl 1:S3. Abstract.
Walsh PC. Intravenous zoledronic acid in postmenopausal women with low bone mineral density. J Urol. 2002 Oct;168(4 Pt 1):1643. No abstract available.
PubMed 12356057Smith MR, Eastham J, Gleason DM, Shasha D, Tchekmedyian S, Zinner N. Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer. J Urol. 2003 Jun;169(6):2008-12. doi: 10.1097/01.ju.0000063820.94994.95.
PubMed 12771706
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Dosing of Zoledronic Acid in Cancer Therapy Induced Bone Loss (CTIBL)
- ClinicalTrials.gov ID
- NCT00712985
- Acronym / sponsor ID
- CTIBL / CZOL446H US113
- Conditions
- Breast Cancer
- Keywords
- Breast cancer, aromatase inhibitors
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Sep 2005
- Primary completion
- Mar 2011 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 11 Jul 2008 (estimated)
- Results
- Posted 24 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research is to establish if a once a year dose of Zoledronic Acid is sufficient to suppress and maintain urine and serum bone density markers (NTx) and serum CTx within normal range at 12 months post-dosing in postmenopausal early breast cancer patients receiving additional treatment with non-steroidal aromatase inhibitors.
Detailed description
Bone metastases are frequently one of the first signs of disseminated disease in cancer patients. Skeletal complications due to metastatic disease include (severe) bone pain, spinal cord compromise, pathological fractures, and hypercalcemia.
Zoledronic acid is a member of a class of compounds known as bisphosphonates. Bisphosphonates are effective inhibitors of osteoclastic bone resorption and have demonstrated therapeutic efficacy in the treatments of hypercalcemia of malignancy, lytic bone disease associated with multiple myeloma, and mixed lytic and blastic bone metastases associated with breast cancer. The precise mechanism by which bisphosphonates inhibit osteoclast function is not fully understood, but may include a direct toxic effect on mature osteoclasts, an inhibition of osteoclast production from precursor cells, and an impairment of osteoclast chemotaxis to sites of active bone resorption. Osteoclasts are specialized bone cells which erode mineralized bone by secreting acids and lysosomal enzymes. In normal bone remodeling, osteoclastic bone resorption is coupled to and is in equilibrium with osteoblastic bone formation. The lytic bone destruction associated with malignant bone metastases develops because tumor cells synthesize and release soluble factors that stimulate osteoclasts to resorb bone. The osteoclastic activating factors released by tumor cells include parathyroid hormone-related peptide (PTHrP), growth factors, and cytokines. The malignant activation of osteoclasts results in a disruption of normal bone remodeling wherein the equilibrium between bone resorption and bone formation is shifted toward increased bone resorption. This relative increase in osteoclastic bone resorption results in a net loss of bone. Thus, the predominant role of the osteoclast in the pathogenesis of bone destruction and the inhibitory effects of bisphosphonates on osteoclast function have formed the rationale for the use of bisphosphonates in the treatment of osteolytic bone metastases. The common role, regardless of tumor type, of the osteoclast as the mediator of bone destruction in metastatic skeletal disease is indicated by the inhibitory effects of bisphosphonates on tumor-induced osteolysis in animal models utilizing various malignant cell lines and the effectiveness of bisphosphonates in the therapy of tumor-induced hypercalcemia arising from any type of cancer. Moreover, recent studies have specifically shown that therapy with the bisphosphonate pamidronate (Aredia) combined with antineoplastic therapy significantly reduces the proportion of patients having skeletal complications due to the lytic bone disease associated with multiple myeloma and breast cancer compared to antineoplastic therapy alone.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Zometa (Zoledronic Acid) X 1 dose | Experimental | Drug: ZometaZometa (Zoledronic Acid) 5 mg IV X 1 dose |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Postmenopausal women with Stage I, II or IIIa breast cancer being treated with a non-steroidal Aromatase Inhibitor (AI) .Negative bone scan (no bone metastases).
- Calculated creatinine clearance > 40 ml/min
- Documented T score of less than or equal to -1.5 on Dual Energy X-ray Absorptiionmetry (DXA) scan at the lumbar spine or femoral neck within 3 months prior to screening.
- Urine NTx > 50 nano moles(nM)based on second morning void.
- Signed informed consent.
Key exclusion criteria (23 listed)
- Bone Metastases.
- Any woman of child bearing potential.
- Patients with fractures occurring within three months prior to randomization. - Greater than a 2+ protein on urine dipstick without evidence of contamination or bacteriuria (may be repeated one time, at least a day apart).
- Calculated creatinine clearance less than 30 mL/min at screening.
- Serum calcium > 2.75 mmol/L (11.0 mg/dL) or < 2.00 mmol/L (8.0 mg/dL).
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 |
|---|---|---|
| ZometaAlso: Zoledronic AcidZometa (Zoledronic Acid) 5 mg IV over 15 minutes in a one time dose | Drug | Zometa (Zoledronic Acid) X 1 dose |
Primary outcome
Number of Participants With Urine and Serum NTx and Serum CTx Within Normal Range at 12 Months
Time frame: One year
17 women with early breast cancer receiving adjuvant Aromatase Inhibitor (AI) therapy were treated with a single 5 mg IV dose of zoledronic acid. Urine and serum NTx and serum CTx were measured at baseline and month 12.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12090977Baum M, Budzar AU, Cuzick J, Forbes J, Houghton JH, Klijn JG, Sahmoud T; ATAC Trialists' Group. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet. 2002 Jun 22;359(9324):2131-9. doi: 10.1016/s0140-6736(02)09088-8.
- Background: PubMed 14551341Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Therasse P, Palmer MJ, Pater JL. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med. 2003 Nov 6;349(19):1793-802. doi: 10.1056/NEJMoa032312. Epub 2003 Oct 9.
- Background: PubMed 15014181Coombes RC, Hall E, Gibson LJ, Paridaens R, Jassem J, Delozier T, Jones SE, Alvarez I, Bertelli G, Ortmann O, Coates AS, Bajetta E, Dodwell D, Coleman RE, Fallowfield LJ, Mickiewicz E, Andersen J, Lonning PE, Cocconi G, Stewart A, Stuart N, Snowdon CF, Carpentieri M, Massimini G, Bliss JM, van de Velde C; Intergroup Exemestane Study. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004 Mar 11;350(11):1081-92. doi: 10.1056/NEJMoa040331.
- BackgroundBIG 1-98 Collaborative Group. Letrozole versus tamoxifen as adjuvant endocrine therapy for postmenopausal women with receptor-positive breast cancer. BIG 1-98: a prospective randomized double-blind phase III study. Breast. 2005;14:Suppl 1:S3. Abstract.
- Background: PubMed 12356057Walsh PC. Intravenous zoledronic acid in postmenopausal women with low bone mineral density. J Urol. 2002 Oct;168(4 Pt 1):1643. No abstract available.
- Background: PubMed 12771706Smith MR, Eastham J, Gleason DM, Shasha D, Tchekmedyian S, Zinner N. Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer. J Urol. 2003 Jun;169(6):2008-12. doi: 10.1097/01.ju.0000063820.94994.95.
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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.
Allan Lipton, MD principal investigator
Milton S. Hershey Medical Center
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 Zometa in people with Breast Cancer, run by Milton S. Hershey Medical Center at 1 site in United States.
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 8 inclusion and 23 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 24 Apr 2014. 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 United States. 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 24 Apr 2014). 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?
Number of Participants With Urine and Serum NTx and Serum CTx Within Normal Range at 12 Months (time frame: One year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00712985, which also lists 6 linked publications.
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 24 Apr 2014.