NCT00171340

Brief Summary

Post-menopausal breast cancer patients will receive letrozole 2.5 mg daily for the treatment of breast cancer and will be randomized to a treatment group to receive either upfront zoledronic acid 4 mg IV 15-minute infusion every 6 months or delayed start zoledronic acid 4 mg IV 15-minute infusion every 6 months. Delayed start zoledronic acid will be initiated when either the Bone Mineral Density T-score is below -2 Standard Deviations at either the lumbar spine or hip or any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the month 36 scheduled visit. Letrozole 2.5 mg will be given daily for 5 years.

Trial Health

98
On Track

Trial Health Score

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

Strong global presence with extensive site network
Enrollment
1,065

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started May 2003

Longer than P75 for phase_3

Geographic Reach
28 countries

106 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

May 1, 2003

Completed
2.4 years until next milestone

First Submitted

Initial submission to the registry

September 12, 2005

Completed
3 days until next milestone

First Posted

Study publicly available on registry

September 15, 2005

Completed
4.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2010

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

May 26, 2011

Completed
Last Updated

April 16, 2012

Status Verified

April 1, 2012

Enrollment Period

6.8 years

First QC Date

September 12, 2005

Results QC Date

March 22, 2011

Last Update Submit

April 10, 2012

Conditions

Keywords

Bone LossOsteopeniaBreast cancerletrozolezoledronic acidpostmenopausal

Outcome Measures

Primary Outcomes (1)

  • Percentage Change in Bone Mineral Density (BMD) of the Lumbar Spine (L2-L4) at 12 Months of Therapy.

    Bone Mineral Density (g/cm\^2) of the Lumbar Spine (L2-L4) as measured by energy x-ray absorptiometry (DXA).

    Baseline, 12 months

Secondary Outcomes (4)

  • Percentage Change in Bone Mineral Density (BMD) of the Lumbar Spine (L2-L4) at 2, 3, 4 and 5 Years of Therapy.

    Baseline, 2 years. Baseline, 3 years. Baseline, 4 years. Baseline, 5 years.

  • Percentage Change in Bone Mineral Density (BMD)of the Lumbar Spine (L1-L4) Over 5 Years of Therapy.

    Baseline, 5 years.

  • Percentage Change in Bone Mineral Density (BMD) of the Total Hip at 12 Months, 2 Years, 3 Years, 4 Years and 5 Years After Therapy.

    Baseline, 12 months. Baseline, 2 years. Baseline, 3 years. Baseline, 4 years. Baseline, 5 years.

  • Percentage of Participants With Clinical Fractures at 3 Years of Therapy Which Were Not Present at Baseline

    Baseline,3 years

Study Arms (2)

Upfront Zoledronic Acid

EXPERIMENTAL

Zolendronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.

Drug: Zoledronic acidDrug: Letrozole

Delayed Zoledronic Acid

EXPERIMENTAL

Zolendronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score \<= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.

Drug: Zoledronic acidDrug: Letrozole

Interventions

Zolendronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months.

Also known as: ZOL446, Zometa®
Delayed Zoledronic AcidUpfront Zoledronic Acid

Letrozole tablets 2.5 mg/day taken orally for 5 years.

Also known as: Femara®
Delayed Zoledronic AcidUpfront Zoledronic Acid

Eligibility Criteria

Sexfemale
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Stage I-IIIa breast cancer
  • Postmenopausal or recently postmenopausal
  • Recent surgery for breast cancer
  • Estrogen Receptor positive and/or progesterone receptor positive hormone receptor status
  • No prior treatment with letrozole

You may not qualify if:

  • Metastatic disease
  • Invasive bilateral disease
  • Clinical or radiological evidence of existing fracture in spine or hip
  • Prior treatment with IV bisphosphonates in the past 12 months
  • Current treatment with oral bisphosphonates ( must be discontinued within 3 weeks of baseline evaluation)
  • Use of Tibolone within 6 months
  • Prior use of parathyroid hormone for more than 1 week
  • Previous or concomitant malignancy
  • Abnormal renal function
  • History of disease effecting bone metabolism

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (106)

Novartis Investigative Site

Buenos Aires, Argentina

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Novartis Investigative Site

Rosario Santa Fe, Argentina

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New South Wales, Australia

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Perth, Australia

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South Australia, Australia

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Victoria, Australia

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Bonheiden, Belgium

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Brasschaat, Belgium

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Brussels, Belgium

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Leuven, Belgium

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Wilrijk, Belgium

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Porto Alegre, Brazil

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São Paulo, Brazil

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Santiago, Chile

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Beijing, China

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Shanghai, China

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Medellín, Colombia

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Nemocnice, Czechia

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Cairo, Egypt

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Pori, Finland

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Turku, Finland

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Bordeaux, France

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Le Havre, France

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Montpellier, France

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Poitiers, France

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Saint-Cloud, France

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Augsberg, Germany

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Berlin, Germany

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Ebersberg, Germany

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Frankfurt, Germany

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Halberstadt, Germany

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Hamburg, Germany

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Hoyerswerda, Germany

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Kassel, Germany

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Kiel, Germany

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Munich, Germany

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München, Germany

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Neunkirchen, Germany

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Rostock, Germany

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Stadthagen, Germany

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Stendal, Germany

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Trier, Germany

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Tübingen, Germany

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Wiesbaden, Germany

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Guatemala City, Guatemala

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Hong Kong, Hong Kong

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Ancona, Italy

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Aviano, 33081, Italy

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Bergamo, Italy

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Catanzaro, 88100, Italy

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Florence, 50139, Italy

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Genova, Italy

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Meldola, Italy

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Modena, Italy

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Orbassano Torino, Italy

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Perugia, Italy

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Torino, Italy

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Varese, Italy

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Distrito Federal, Mexico

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Almere Stad, Netherlands

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Arnhem, Netherlands

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Ede, Netherlands

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Eindhoven, Netherlands

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Hoogeveen, Netherlands

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Leiden, Netherlands

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Nijmegen, Netherlands

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The Hague, Netherlands

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Utrecht, Netherlands

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Hamilton, New Zealand

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Wellington, New Zealand

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Jesus Maria, Peru

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La Victoria, Peru

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Surquillo, Peru

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Cebu City, Philippines

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Quezon City, Philippines

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Coimbra, Portugal

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Gyeonggi-do, South Korea

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Seoul, 110, South Korea

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Seoul, 137, South Korea

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Seoul, 138, South Korea

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Seoul, 139, South Korea

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Barcelona, Spain

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Córdoba, Spain

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Gea de Albarracín, Spain

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Ibáñez, Spain

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la Masó, Spain

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Villaroel, Spain

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Bern, Switzerland

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Locarno, Switzerland

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Lugano, Switzerland

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Chang-hua, 500, Taiwan

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Taipei, 100, Taiwan

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Taipei, 105, Taiwan

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Taipei, 112, Taiwan

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Novartis Investigative Site

Bangkok, 10400, Thailand

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Bangkok, Thailand

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Ratchathew

Khonkaen, 40002, Thailand

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Birmingham, United Kingdom

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Essex, United Kingdom

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Manchester, United Kingdom

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New Castle Upon Tyne, United Kingdom

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Nottingham, United Kingdom

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Plymouth, United Kingdom

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Sheffield, United Kingdom

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Swansea, United Kingdom

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Caracas, Venezuela

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Related Publications (2)

  • 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.

  • Coleman R, de Boer R, Eidtmann H, Llombart A, Davidson N, Neven P, von Minckwitz G, Sleeboom HP, Forbes J, Barrios C, Frassoldati A, Campbell I, Paija O, Martin N, Modi A, Bundred N. Zoledronic acid (zoledronate) for postmenopausal women with early breast cancer receiving adjuvant letrozole (ZO-FAST study): final 60-month results. Ann Oncol. 2013 Feb;24(2):398-405. doi: 10.1093/annonc/mds277. Epub 2012 Oct 9.

MeSH Terms

Conditions

Bone Diseases, MetabolicBreast Neoplasms

Interventions

Zoledronic AcidLetrozole

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

DiphosphonatesOrganophosphonatesOrganophosphorus CompoundsOrganic ChemicalsImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsNitrilesTriazoles

Results Point of Contact

Title
Study Director
Organization
Novartis Pharmaceuticals

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

September 12, 2005

First Posted

September 15, 2005

Study Start

May 1, 2003

Primary Completion

February 1, 2010

Study Completion

February 1, 2010

Last Updated

April 16, 2012

Results First Posted

May 26, 2011

Record last verified: 2012-04

Locations