Breast NeoplasmsPhase 4FEMZONENCT00375752

Efficacy and Safety of Letrozole vs. Letrozole Plus Zoledronic Acid as Endocrine Therapy Before Surgery in Postmenopausal Patients With Breast Cancer

A Phase 4 study testing Letrozole and Zolendronic Acid in people with Breast Neoplasms, run by Novartis Pharmaceuticals at 27 sites 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

This study will evaluate the safety/efficacy of zoledronic acid when given by intravenous infusion every 4 weeks in addition to letrozole as endocrine therapy in postmenopausal patients with hormone responsive breast cancer Read more about this study

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Breast Neoplasms
What is being tested?: Letrozole and Zolendronic Acid
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 168 participants
Where: 27 sitesGermany
Study dates: 1 Jun 2006to 16 Dec 2010
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

Postmenopausal women with primary invasive breast cancer, histologically confirmed by core needle biopsy, whose tumors are estrogen (ER) and / or progesterone (PgR) positive
Clinical Stage T1c (Size ≥ 1.5 cm), T2, T3, T4a, b, c, N0 or N1, M0 (TNM Classification). According to the modified RECIST criteria, tumors of size ≥ 1.5 cm are considered measurable by mammography and can be determined as target lesions).
Tumor measurable by mammography, sonography and clinical examination.
Adequate bone marrow, renal and hepatic function
Good health status (ECOG Performance status of 0, 1 or 2)

Who cannot join

Prior treatment with letrozole or bisphosphonates. Prior and concomitant anti-breast-cancer treatments such as chemotherapy, immunotherapy / biological response modifiers (BRM's), endocrine therapy other than letrozole (including steroids), and radiotherapy. Patients who have received hormone replacement therapy (HRT) will NOT be excluded, provided that HRT is discontinued at least 2 weeks prior to entry into the study.
Patients with unstable angina, or uncontrolled cardiac disease (e.g. Class III and IV New York Heart Association's Functional Classification, see Appendix 9) or uncontrolled endocrine disorders.
Evidence of inflammatory breast cancer or distant metastasis.
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).
History of diseases with influence on bone metabolism, such as Paget's disease, Osteogenesis Imperfecta, and primary or secondary hyperthyroidism within the 12 months prior to study entry
Other protocol-defined inclusion/exclusion criteria may apply

Trial locations and contacts

27 sites in 1 country.

City, postcode or hospital

27 sites in 1 country

Germany27 sites

Novartis Investigative Site
Amberg, 92224
Novartis Investigative Site
Berlin, 10365
Novartis Investigative Site
Böblingen, 71032
Novartis Investigative Site
Celle, 29223
Novartis Investigative Site
Cologne, 50924
Novartis Investigative Site
Ebersberg, 85560
Novartis Investigative Site
Erlangen, 91052
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Essen, 45276
Novartis Investigative Site
Esslingen am Neckar, 73730
Novartis Investigative Site
Freiburg im Breisgau, 79106
Novartis Investigative Site
Fürth, 90766
Novartis Investigative Site
Halle, 06110
Novartis Investigative Site
Hamburg, 22457
Novartis Investigative Site
Hamelin, 31785
Novartis Investigative Site
Hanau, 63450
Novartis Investigative Site
Hanover, 30625
Novartis Investigative Site
Heilbronn, 74064
Novartis Investigative Site
Kempten, 87439
Novartis Investigative Site
Leipzig, 04277
Novartis Investigative Site
München, 81377
Novartis Investigative Site
München, 81545
Novartis Investigative Site
München, 81675
Novartis Investigative Site
Neunkirchen, 66538
Novartis Investigative Site
Rheinfelden, 79618
Novartis Investigative Site
Ulm, 89070
Novartis Investigative Site
Ulm, 89703

Other trials in Germany

About this study

Official title: Neoadjuvant Therapy for Postmenopausal Women With ER and/or PgR Positive Breast Cancer. A Randomized Open Phase II Trial Evaluating the Efficacy of a 6 Months Preoperative Treatment With Letrozole (2.5 mg/Day) With or Without Zoledronic Acid (4 mg Every 4 Weeks)

Read the detailed description

Open-label, multicenter, randomized phase II trial over approx 6.5 months of neoadjuvant treatment with letrozole with or without zoledronic acid in postmenopausal patients with primary breast cancer. A total of approximately 850 patients were originally planned to be enrolled; primary study endpoint was the objective response rate (according to modified RECIST criteria) after 6 months of treatment. After the core study, patients willing to participate were followed-up for further 5 years.

Conditions: Breast Neoplasms
Being tested: Letrozole, Zolendronic Acid
Keywords: Breast cancer, Anti tumor potential, Letrozole, Zoledronic acid, Neoadjuvant treatment, Hormone responsive breast cancer
Medical subject headings: Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LetrozoleDrug
2.5 mg.tablet.
Zolendronic AcidDrug
4 mg or an adjusted dose based on renal function in 100 ml physiologic (o.9%) normal saline, (as an intravenous infusion over no less than 15 minutes)

Study groups in NCT00375752
Study group	Role	What they receive
Letrozole	Active comparator	Letrozole 2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvent treatment Receives: Drug: Letrozole
Zolendronic Acid + Letrozole	Experimental	2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvant treatment plus zoledronic acid 4 mg i.v. q4w Receives: Drug: Letrozole; Drug: Zolendronic Acid

What is being measured

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

Tumor Response Rate (Complete Response (CR) or Partial Response (PR)) Based on MRI- or Mammography and/or Sonography According to Modified RECIST Criteria at Month 6
Sum of longest diameter for all target lesions was reported as baseline sum LD. Baseline sum LD was used as reference to characterize objective tumor response. Response Evaluation Criteria in Solid Tumors has 4 response categories. CR (complete response) = disappearance of all target lesions, PR (partial response)= 30% decrease in sum of longest diameter of target lesions, PD (progressive disease) = 20% increase in the sum of the longest diameter of target lesions and SD(stable disease)=small changes that do not meet criteria. Analysis was underpowered due to insufficient recruitment rate.
Measured: 6 months

Secondary outcomes (4)

Best RECIST Response Based on Central Review at 6 Mos
Best response is defined as the best response the patients has reached during the 6 months of treatment. Response Evaluation Criteria in Solid Tumors (RECIST) has 4 response categories. CR (complete response) = disappearance of all target lesions, PR (partial response) = 30% decrease in the sum of the longest diameter of target lesions, PD (progressive disease) = 20% increase in the sum of the longest diameter of target lesions and SD (stable disease) = small changes that do not meet criteria.
Measured: 6 Months
Number of Patients With Breast Conserving Surgery at 6 Months
Measured: Every 6 months
Change From Baseline in Tumor Size (Longest Diameter) at Month 6
Tumor size (sum of longest diameter)was analyzed based on the diameters values provided with the central review.
Measured: Baseline, Month 6
Mean Changes From Baseline in FACT-B Total Score at 6 Months (ITT, Data as Observed)
The FACT-B total score is calculated by summing all five unweighted subscale scores, with total scores in the range of 0-144.To Derive a FACT-B total score: all sections added together The higher the score the better the QoL
- + __________ + __________ + __________ + __________ =________=FACT-B Total score (PWB score) (SWB score) (EWB score) (FWB score) (BCS score)
Measured: baseline and 6 mos

Timeline

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

1 Jun 200616 Dec 2010

First posted13 Sep 2006 (estimated)
Study start1 Jun 2006
Primary completion16 Dec 2010
Study completion16 Dec 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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Breast NeoplasmsStudies 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: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 168 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00375752
Sponsor's protocol ID: CZOL446GDE19
Other IDs: 2004-004007-37, 2004
Acronym: FEMZONE
Status last verified: Jun 2017
First submitted: 11 Sep 2006
Last updated: 26 Jun 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Undecided

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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 26 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Neoadjuvant Therapy for Postmenopausal Women With ER and/or PgR Positive Breast Cancer. A Randomized Open Phase II Trial Evaluating the Efficacy of a 6 Months Preoperative Treatment With Letrozole (2.5 mg/Day) With or Without Zoledronic Acid (4 mg Every 4 Weeks)
ClinicalTrials.gov ID: NCT00375752
Acronym / sponsor ID: FEMZONE / CZOL446GDE19
Conditions: Breast Neoplasms
Keywords: Breast cancer, Anti tumor potential, Letrozole, Zoledronic acid, Neoadjuvant treatment, Hormone responsive breast cancer
Phase: Phase 4
Study type: Interventional
Recruitment status: Terminated
Enrolment: 168 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 1 Jun 2006 (actual)
Primary completion: 16 Dec 2010 (actual)
Study completion: 16 Dec 2010 (actual)
First posted: 13 Sep 2006 (estimated)
Results: Posted 25 Apr 2012

Clinical summary

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Letrozole	Active comparator	Drug: LetrozoleLetrozole 2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvent treatment
Zolendronic Acid + Letrozole	Experimental	Drug: Letrozole, Drug: Zolendronic Acid2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvant treatment plus zoledronic acid 4 mg i.v. q4w

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)

Postmenopausal women with primary invasive breast cancer, histologically confirmed by core needle biopsy, whose tumors are estrogen (ER) and / or progesterone (PgR) positive
Clinical Stage T1c (Size ≥ 1.5 cm), T2, T3, T4a, b, c, N0 or N1, M0 (TNM Classification). According to the modified RECIST criteria, tumors of size ≥ 1.5 cm are considered measurable by mammography and can be determined as target lesions).
Tumor measurable by mammography, sonography and clinical examination.
Adequate bone marrow, renal and hepatic function
Good health status (ECOG Performance status of 0, 1 or 2)

Key exclusion criteria (6 listed)

Prior treatment with letrozole or bisphosphonates. Prior and concomitant anti-breast-cancer treatments such as chemotherapy, immunotherapy / biological response modifiers (BRM's), endocrine therapy other than letrozole (including steroids), and radiotherapy. Patients who have received hormone replacement therapy (HRT) will NOT be excluded, provided that HRT is discontinued at least 2 weeks prior to entry into the study.
Patients with unstable angina, or uncontrolled cardiac disease (e.g. Class III and IV New York Heart Association's Functional Classification, see Appendix 9) or uncontrolled endocrine disorders.
Evidence of inflammatory breast cancer or distant metastasis.
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).
History of diseases with influence on bone metabolism, such as Paget's disease, Osteogenesis Imperfecta, and primary or secondary hyperthyroidism within the 12 months prior to study entry

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
Letrozole2.5 mg.tablet.	Drug	Letrozole, Zolendronic Acid + Letrozole
Zolendronic Acid4 mg or an adjusted dose based on renal function in 100 ml physiologic (o.9%) normal saline, (as an intravenous infusion over no less than 15 minutes)	Drug	Zolendronic Acid + Letrozole

Primary outcome

Tumor Response Rate (Complete Response (CR) or Partial Response (PR)) Based on MRI- or Mammography and/or Sonography According to Modified RECIST Criteria at Month 6
Time frame: 6 months
Sum of longest diameter for all target lesions was reported as baseline sum LD. Baseline sum LD was used as reference to characterize objective tumor response. Response Evaluation Criteria in Solid Tumors has 4 response categories. CR (complete response) = disappearance of all target lesions, PR (partial response)= 30% decrease in sum of longest diameter of target lesions, PD (progressive disease) = 20% increase in the sum of the longest diameter of target lesions and SD(stable disease)=small changes that do not meet criteria. Analysis was underpowered due to insufficient recruitment rate.

4 secondary outcomes

Best RECIST Response Based on Central Review at 6 Mos
Time frame: 6 Months
Number of Patients With Breast Conserving Surgery at 6 Months
Time frame: Every 6 months
Change From Baseline in Tumor Size (Longest Diameter) at Month 6
Time frame: Baseline, Month 6
Mean Changes From Baseline in FACT-B Total Score at 6 Months (ITT, Data as Observed)
Time frame: baseline and 6 mos

Results and safety

Results posted to the registry on 25 Apr 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Letrozole (LET)	79	67
Letrozole +Zoledronic Acid (LET+ZOL)	89	74

Primary outcome: Tumor Response Rate (Complete Response (CR) or Partial Response (PR)) Based on MRI- or Mammography and/or Sonography According to Modified RECIST Criteria at Month 6

Time frame: 6 months. Number (95% Confidence Interval). Unit: percentage of participants

Measure	Letrozole (LET) n = 66	Letrozole +Zoledronic Acid (LET+ZOL) n = 65
Value	54.5 (41.8 to 66.9)	69.2 (56.6 to 80.1)

Letrozole (LET) vs Letrozole +Zoledronic Acid (LET+ZOL): Odds Ratio (OR): 14.7 (95% CI -1.8 to 31.1), p = 0.106, Fisher Exact

Population analysed: The modified intent-to-treat (mITT) population included all patients of the ITT population for whom at least one post-baseline assessment of tumor response according to modified RECIST made by central review was available.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: through study completion. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Letrozole	3 of 79 (3.8%)	56 of 79 (70.9%)	Not reported
Letrozole Plus Zoledronic Acid	14 of 89 (15.7%)	67 of 89 (75.3%)	Not reported

Limitations and caveats (from the sponsor): Study terminated after 178 patients screened and 168 randomized, due to insufficient recruitment rate (no safety issues decided the reason to terminate study). LPLV for study was on 13-DEC-2010. LPLV of the 5-year follow-up period was on 03-FEB-2016.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2017.
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.
Individual participant dataSharing planned: Undecided

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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

Novartis Pharmaceuticals study director

Novartis Pharmeceuticals

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

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Letrozole and Zolendronic Acid in people with Breast Neoplasms, run by Novartis Pharmaceuticals at 27 sites 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 6 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 26 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites 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. 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 Apr 2012). 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?

Tumor Response Rate (Complete Response (CR) or Partial Response (PR)) Based on MRI- or Mammography and/or Sonography According to Modified RECIST Criteria at Month 6 (time frame: 6 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 NCT00375752, 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 26 Jun 2017.