Primary Hormone Receptor Negative Breast Cancer in Premenopausal WomenPhase 4NCT00333229

A Study of Zoledronic Acid in the Prevention of Cancer Therapy-induced Bone Loss

A Phase 4 study testing Zoledronic Acid in people with Primary Hormone Receptor Negative Breast Cancer in Premenopausal Women, run by Novartis Pharmaceuticals at 1 site in Germany.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Breast cancer and osteoporosis are two of the most frequent diseases in women. Estrogen may be associated with bone loss and the risk of breast cancer because of its potent effects on the mitotic activity of breast epithelium and on bone turnover. Read more about this study

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Primary Hormone Receptor Negative Breast Cancer in Premenopausal Women
What is being tested?: Zoledronic Acid
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 11 participants
Where: 1 siteGermany
Study dates: Mar 2006to Dec 2013
Phase: Phase 4
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 with histologically confirmed incident invasive breast cancer (T1-4) with no evidence of regional lymph node metastasis (N0) or distant metastasis (M0) and after complete primary tumor resection and axillary lymph node dissection less than 90 days before start of study drug treatment.
Hormone receptor status is negative
Patient is premenopausal (spontaneous and regular menses with premenopausal estradiol levels (>10ng/dL)
Patient receives adjuvant standard chemotherapy with approved cytotoxic chemotherapeutic drugs (e.g. AC 4-6 cycles) (prior neoadjuvant CT is allowed)
Bone density at study entry > -2.5 T-Score

Who cannot join

Prior treatment with bisphosphonates and estrogens or treatments for osteoporosis in addition to calcium and vitamin D
Severe physical or psychological concomitant diseases and other known concurrent, severe medical disorder jeopardizing the life of the patient in the immediate future (e.g., myocardial infarction in previous six months, angina pectoris despite treatment, uncontrolled severe arterial hypertension, progressive cardiac or respiratory failure)
Known hypersensitivity to bisphosphonates
Abnormal renal function
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 and recent (within 6 weeks) or planned dental or jaw surgery (e.g. extraction, implants)

Trial locations and contacts

1 site in 1 country.

Germany1 site

Novartis Investigative Site
Marburg, 35043

Other trials in Germany

About this study

Official title: Influence of Zoledronic Acid on Bone Mineral Density and Bone Ultrasonometry in Premenopausal Women With Hormone Receptor Negative Breast Cancer and Adjuvant Chemotherapeutic Treatment

This study is will assess the safety and efficacy of Zoledronic acid 4 mg, given every 3 months over 24 months, in improving bone mineral density in premenopausal women with hormone receptor negative breast cancer and adjuvant chemotherapeutic treatment compared to placebo.

This study is not recruiting patients in the United States.

Conditions: Primary Hormone Receptor Negative Breast Cancer in Premenopausal Women
Being tested: Zoledronic Acid, Placebo
Keywords: Breast Cancer, premenopausal, Bone Mineral density, Cancer therapy induced bone loss, zoledronic acid
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
4 mg zoledronic acid in 5 mL concentrate solution. Plastic vials.
PlaceboDrug
Matching Placebo

Study groups in NCT00333229
Study group	Role	What they receive
Zoledronic Acid	Experimental	Patients randomized into the Zometa arm received a total of 8 study drug infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months. Receives: Drug: Zoledronic Acid
Placebo	Placebo comparator	Patients randomized into the Placebo Arm received a total of 8 placebo infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Bone Mineral Density (BMD) Measured by DXA at Lumbar Spine (L2-L4) Between Baseline and 24 Months.
Measured: 24 months

Secondary outcomes (4)

Bone Mineral Density (BMD) Measured by QUS at os Calcis and Phalanges After 24 Months
Measured: 2 years
Course of Biochemical Markers of Bone Turn Over (FSH, Estradiol (E2), Osteocalcin, PINP, Procollagene-I-peptid, Deoxypyridinoline in Serum)
Measured: 2 years
Pathologic Fractures During 24 Month
Measured: 2 years
Development of Metastases as Assessed by X-ray, CT, or MRI During 24 Months and During 60 Months
Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2006Dec 2013

First posted2 Jun 2006 (estimated)
Study startMar 2006
Primary completionDec 2013
Study completionDec 2013

Why it stopped: Due to rare patient population, planned number of patients could not be recruited in a reasonable timeframe. Recruitment was stopped prematurely.

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 (1)Papers the sponsor has linked to this study.
Other trials for Primary Hormone Receptor Negative Breast Cancer in Premenopausal WomenStudies 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 4
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 11 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00333229
Sponsor's protocol ID: CZOL446GDE13
Other IDs: 2004-002831-14, 2004
Status last verified: Nov 2014
First submitted: 31 May 2006
Last updated: 25 Nov 2014
Results posted: Yes, on ClinicalTrials.gov

Publications

Adams A, Jakob T, Huth A, Monsef I, Ernst M, Kopp M, Caro-Valenzuela J, Wockel A, Skoetz N. Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD013451. doi: 10.1002/14651858.CD013451.pub2.
PubMed 38979716

Study at a glance

From the registry record, last updated by the sponsor on 25 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Influence of Zoledronic Acid on Bone Mineral Density and Bone Ultrasonometry in Premenopausal Women With Hormone Receptor Negative Breast Cancer and Adjuvant Chemotherapeutic Treatment
ClinicalTrials.gov ID: NCT00333229
Acronym / sponsor ID: CZOL446GDE13
Conditions: Primary Hormone Receptor Negative Breast Cancer in Premenopausal Women
Keywords: Breast Cancer, premenopausal, Bone Mineral density, Cancer therapy induced bone loss, zoledronic acid
Phase: Phase 4
Study type: Interventional
Recruitment status: TerminatedReason stopped: Due to rare patient population, planned number of patients could not be recruited in a reasonable timeframe. Recruitment was stopped prematurely.
Enrolment: 11 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Mar 2006
Primary completion: Dec 2013 (actual)
Study completion: Dec 2013 (actual)
First posted: 2 Jun 2006 (estimated)
Results: Posted 25 Nov 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study is not recruiting patients in the United States.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Zoledronic Acid	Experimental	Drug: Zoledronic AcidPatients randomized into the Zometa arm received a total of 8 study drug infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months.
Placebo	Placebo comparator	Drug: PlaceboPatients randomized into the Placebo Arm received a total of 8 placebo infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months.

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Female patients with histologically confirmed incident invasive breast cancer (T1-4) with no evidence of regional lymph node metastasis (N0) or distant metastasis (M0) and after complete primary tumor resection and axillary lymph node dissection less than 90 days before start of study drug treatment.
Hormone receptor status is negative
Patient is premenopausal (spontaneous and regular menses with premenopausal estradiol levels (>10ng/dL)
Patient receives adjuvant standard chemotherapy with approved cytotoxic chemotherapeutic drugs (e.g. AC 4-6 cycles) (prior neoadjuvant CT is allowed)
Bone density at study entry > -2.5 T-Score

Key exclusion criteria (5 listed)

Prior treatment with bisphosphonates and estrogens or treatments for osteoporosis in addition to calcium and vitamin D
Severe physical or psychological concomitant diseases and other known concurrent, severe medical disorder jeopardizing the life of the patient in the immediate future (e.g., myocardial infarction in previous six months, angina pectoris despite treatment, uncontrolled severe arterial hypertension, progressive cardiac or respiratory failure)
Known hypersensitivity to bisphosphonates
Abnormal renal function
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 and recent (within 6 weeks) or planned dental or jaw surgery (e.g. extraction, implants)

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 Acid4 mg zoledronic acid in 5 mL concentrate solution. Plastic vials.	Drug	Zoledronic Acid
PlaceboMatching Placebo	Drug	Placebo

Primary outcome

Change in Bone Mineral Density (BMD) Measured by DXA at Lumbar Spine (L2-L4) Between Baseline and 24 Months.
Time frame: 24 months

4 secondary outcomes

Bone Mineral Density (BMD) Measured by QUS at os Calcis and Phalanges After 24 Months
Time frame: 2 years
Course of Biochemical Markers of Bone Turn Over (FSH, Estradiol (E2), Osteocalcin, PINP, Procollagene-I-peptid, Deoxypyridinoline in Serum)
Time frame: 2 years
Pathologic Fractures During 24 Month
Time frame: 2 years
Development of Metastases as Assessed by X-ray, CT, or MRI During 24 Months and During 60 Months
Time frame: 2 years

Results and safety

Results posted to the registry on 25 Nov 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Zoledronic Acid	6	6
Placebo	5	4

Primary outcome: Change in Bone Mineral Density (BMD) Measured by DXA at Lumbar Spine (L2-L4) Between Baseline and 24 Months.

Time frame: 24 months

Population analysed: Analysis was not completed as study was not adequately powered due to premature study termination.

4 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	1 of 5 (20%)	5 of 5 (100%)	Not reported
Zoledronic Acid	1 of 6 (16.7%)	6 of 6 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 38979716Adams A, Jakob T, Huth A, Monsef I, Ernst M, Kopp M, Caro-Valenzuela J, Wockel A, Skoetz N. Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD013451. doi: 10.1002/14651858.CD013451.pub2.
Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.Link provided by the sponsor.

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

Novartis Pharmaceuticals study director

Novartis Pharmeceuticals

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Zoledronic Acid in people with Primary Hormone Receptor Negative Breast Cancer in Premenopausal Women, run by Novartis Pharmaceuticals at 1 site in Germany.

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 5 inclusion and 5 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: stopped early, as of the sponsor's last update on 25 Nov 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 Germany. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 25 Nov 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?

Change in Bone Mineral Density (BMD) Measured by DXA at Lumbar Spine (L2-L4) Between Baseline and 24 Months. (time frame: 24 months). 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 NCT00333229, which also lists 1 linked publication.

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 25 Nov 2014.