NCT00332709

Brief Summary

This was a prospective, randomized, open-label, two arm phase III trial designed to evaluate the efficacy and safety of zoledronic acid in preventing bone loss in postmenopausal women with operable breast cancer who had received 4 to 6 years of adjuvant tamoxifen therapy after resection of the tumor. Patients were treated with letrozole 2.5 mg orally per day or letrozole 2.5 mg orally per day in combination with zoledronic acid 4 mg/6 months as an infusion. This trial did not recruit patients in the United States.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
83

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Jan 2006

Longer than P75 for phase_3

Geographic Reach
1 country

23 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2006

Completed
5 months until next milestone

First Submitted

Initial submission to the registry

May 31, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 2, 2006

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2010

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

November 16, 2011

Completed
Last Updated

November 16, 2011

Status Verified

October 1, 2011

Enrollment Period

4.6 years

First QC Date

May 31, 2006

Results QC Date

August 11, 2011

Last Update Submit

October 10, 2011

Conditions

OsteoporosisPostmenopausal

Keywords

Breast cancerpostmenopausalbone mineral densityZoledronic acidLetrozoleextended adjuvant treatment.Postmenopausal women with primary hormone receptor positive breast cancer

Outcome Measures

Primary Outcomes (4)

  • Change in Bone Mineral Density (BMD) From Baseline to Month 36

    Change in bone mineral density (BMD) measured by dual X-ray absorptiometry (DXA) in lumbar spine (L1-L4). Change calculated by (Month 36 BMD-Baseline BMD)/Baseline BMD\*100.

    at 36 months as compared to baseline

  • Percent Change in Bone Mineral Density (BMD) From Baseline to Month 36

    Bone Mineral Density is measured by dual energy x-ray absorptiometry (DXA) scan. ANCOVA model was used in the analysis where: Variable = Baseline, Center, Treatment BMD = (Month 36 BMD-Baseline BMD)/Baseline BMD\*100.

    Baseline, Month 36

  • Change in T-score From Baseline to Month 36

    BMD measured by DXA (dual energy x-ray absorptiometry) at lumbar spine, L1-L4. The T-Score is a comparison of a patient's BMD to that of a healthy 30 year of the same sex and ethnicity. The criteria of the World Health Organization are Normal is a T-Score of 1.0 or higher. Osteopenia is defined as between - 1.0 and -2.5. Osteoporosis is defined as -2.5 or lower, meaning a bone density that is two and half standard deviations below the mean of a 30 year old man/woman.

    Baseline and Month 36

  • Change in Z Score From Baseline to Month 36

    Bone Mineral Density is measured by dual energy x-ray absorptiometry (DXA). The Z-Score is the number of standard deviations a patient's BMD differs from the average BMD of their age, sex and ethnicity. A Z-score of less than minus -1.5 raises concern of factors other than aging as contributing to osteoporosis.

    Baseline, month 36

Secondary Outcomes (5)

  • Change in Bone Mineral Density From Baseline to 12 Months

    Baseline, 12 months

  • Number of Participants With Any Kind of Fractures, by Visit.

    Baseline, Month 6, 12, 18, 24 , 30 and 36

  • Median Disease Free Survival (DFS)

    36 months

  • Change in T-Score From Baseline to Month 12

    Baseline, Month 12

  • Change in Z-Score From Baseline to Month 12

    Baseline, Month 12

Study Arms (2)

Letrozole

EXPERIMENTAL

Letrozole orally 2.5 mg/day for 3 years

Drug: Letrozole

Letrozole + Zoledronic Acid

EXPERIMENTAL

Letrozole orally 2.5mg/day for 3 years; Zoledronic acid 4mg every 6 months by infusion

Drug: LetrozoleDrug: Zoledronic acid

Interventions

LetrozoleDRUG

2.5 mg/day for 3 years

LetrozoleLetrozole + Zoledronic Acid
Zoledronic acidDRUG

4 mg every 6 months

Letrozole + Zoledronic Acid

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Compliant postmenopausal women with primary operable breast cancer after 4 to 6 years of therapy with tamoxifen (end of tamoxifen therapy within last 6 months)
  • Performance status 0-2 (Eastern Cooperative Oncology Group)
  • Patients without severe osteoporosis at study entry
  • No evidence of relapse at the time of randomization
  • Adequate function of bone marrow, kidney, and liver

You may not qualify if:

  • Estrogen- and progesterone-receptor status negative or unknown
  • Completion of adjuvant tamoxifen therapy more than 6 months prior to study start
  • Inflammatory breast cancer
  • Current/active dental problems including infection of the teeth or jawbone, dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw, of exposed bone in the mouth, or of slow healing after dental procedures.
  • Recent (within 6 weeks) or planned dental or jaw surgery
  • History of diseases with influence on bone metabolism such as Paget's disease and primary overactive parathyroid
  • Prior or concomitant therapies: chemotherapy within the last 12 months, intravenous or oral bisphosphonates, systemic corticosteroids, anabolic steroids or growth hormones, Tibolone, parathyroid hormone, systemic sodium fluoride or any drugs known to affect the skeleton (such as calcitonin, mithramycin, or gallium nitrate)
  • Patients with previous or concomitant cancers (not breast cancer) within the past 5 years EXCEPT adequately treated basal or squamous cell skin cancers or in situ cancer of the cervix. Patients with previous other cancer(s) must have been disease-free for at least 5 years.
  • Patients currently receiving oral bisphosphonates must discontinue these at least 3 weeks prior to study start.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (23)

Novartis Investigative Site

Cologne, Germany

Location

Novartis Investigative Site

Deggendorf, Germany

Location

Novartis Investigative Site

Frankfurt am Main, Germany

Location

Novartis Investigative Site

Freiburg im Breisgau, Germany

Location

Novartis Investigative Site

Georgsmarienhütte, Germany

Location

Novartis Investigative Site

Göttingen, Germany

Location

Novartis Investigative Site

Halle, Germany

Location

Novaertis Investigative Site

Hamein, Germany

Location

Novartis Investigative Site

Hanover, Germany

Location

Novartis Investigative Site

Höxter, Germany

Location

Novartis Investigative Site

Ilsede, Germany

Location

Novartis Investigative Site

Jena, Germany

Location

Novartis Investigative Site

Karlsruhe, Germany

Location

Novartis Investigative Site

Leer, Germany

Location

Novartis Investigative Site

Lübeck, Germany

Location

Novartis Investigative Site

Mannheim, Germany

Location

Novartis Investigative Site

Münster, Germany

Location

Novartis Investigative Site

Rostock, Germany

Location

Novartis Investigative Site

Salzgitter, Germany

Location

Novartis Investigative Site

Schwenningen, Germany

Location

Novartis Investigative Site

Stendal, Germany

Location

Novartis Investigative Site

Völklingen, Germany

Location

Novartis Investigative Site

Witten, Germany

Location

Related Publications (1)

  • 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.

    PMID: 38979716DERIVED

MeSH Terms

Conditions

OsteoporosisBreast Neoplasms

Interventions

LetrozoleZoledronic Acid

Condition Hierarchy (Ancestors)

Bone Diseases, MetabolicBone DiseasesMusculoskeletal DiseasesMetabolic DiseasesNutritional and Metabolic DiseasesNeoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

NitrilesOrganic ChemicalsTriazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsDiphosphonatesOrganophosphonatesOrganophosphorus CompoundsImidazoles

Results Point of Contact

Title
Study Director
Organization
Novartis Pharmaceuticals
862-778-8300

Study Officials

  • Novartis Pharmaceuticals

    Novartis Pharmaceuticals

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 31, 2006

First Posted

June 2, 2006

Study Start

January 1, 2006

Primary Completion

August 1, 2010

Study Completion

August 1, 2010

Last Updated

November 16, 2011

Results First Posted

November 16, 2011

Record last verified: 2011-10

Locations

DE(23)