Clinical trial NCT00171340: Zoledronic Acid in the Prevention of Cancer Treatment Related Bone Loss in Postmenopausal Women Receiving Letrozole for Breast Cancer.
Official title: An Open-Label, Randomized, MultiCenter Study to Evaluate the Use of Zolendronic Acid in the Prevention of Cancer Treatment-Related Bone Loss in Postmenopausal Women With Estrogen Positive and/or Progesterone Positive Breast Cancer Receiving Letrozole as Adjuvant Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bone Loss
Breast Cancer
Keywords: Bone Loss
Osteopenia
Breast cancer
letrozole
zoledronic acid
postmenopausal
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2005-09-15
Enrollment: 1065
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Other protocol-defined inclusion criteria may apply.

Exclusion Criteria:

* 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

Other protocol-defined exclusion criteria may apply.

Primary outcomes:
measure: Percentage Change in Bone Mineral Density (BMD) of the Lumbar Spine (L2-L4) at 12 Months of Therapy.
timeFrame: Baseline, 12 months
Secondary outcomes:
measure: Percentage Change in Bone Mineral Density (BMD) of the Lumbar Spine (L2-L4) at 2, 3, 4 and 5 Years of Therapy.
timeFrame: Baseline, 2 years. Baseline, 3 years. Baseline, 4 years. Baseline, 5 years.
measure: Percentage Change in Bone Mineral Density (BMD)of the Lumbar Spine (L1-L4) Over 5 Years of Therapy.
timeFrame: Baseline, 5 years.
measure: 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.
timeFrame: Baseline, 12 months. Baseline, 2 years. Baseline, 3 years. Baseline, 4 years. Baseline, 5 years.
measure: Percentage of Participants With Clinical Fractures at 3 Years of Therapy Which Were Not Present at Baseline
timeFrame: Baseline,3 years
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Rosario Santa Fe
country: Argentina
facility: Novartis Investigative Site
city: New South Wales
country: Australia
facility: Novartis Investigative Site
city: Perth
country: Australia
facility: Novartis Investigative Site
city: South Australia
country: Australia
facility: Novartis Investigative Site
city: Victoria
country: Australia
facility: Novartis Investigative Site
city: Bonheiden
country: Belgium
facility: Novartis Investigative Site
city: Brasschaat
country: Belgium
facility: Novartis Investigative Site
city: Brussels
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Wilrijk
country: Belgium
facility: Novartis Investigative Site
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Medellin
country: Colombia
facility: Novartis Investigative Site
city: Nemocnice
country: Czech Republic
facility: Novartis Investigative Site
city: Cairo
country: Egypt
facility: Novartis Investigative Site
city: Pori
country: Finland
facility: Novartis Investigative Site
city: Turku
country: Finland
facility: Novartis Investigative Site
city: Bordeaux Cedex
country: France
facility: Novartis Investigative Site
city: Le Havre
country: France
facility: Novartis Investigative Site
city: Montpellier Cedex
country: France
facility: Novartis Investigative Site
city: Poitiers Cedex
country: France
facility: Novartis Investigative Site
city: St. Cloud
country: France
facility: Novartis Investigative Site
city: Augsberg
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Ebersberg
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Halberstadt
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hoyerswerda
country: Germany
facility: Novartis Investigative Site
city: Kassel
country: Germany
facility: Novartis Investigative Site
city: Kiel
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Munich
country: Germany
facility: Novartis Investigative Site
city: Neunkirchen
country: Germany
facility: Novartis Investigative Site
city: Rostock
country: Germany
facility: Novartis Investigative Site
city: Stadthagen
country: Germany
facility: Novartis Investigative Site
city: Stendal
country: Germany
facility: Novartis Investigative Site
city: Trier
country: Germany
facility: Novartis Investigative Site
city: Tubingen
country: Germany
facility: Novartis Investigative Site
city: Wiesbaden
country: Germany
facility: Novartis Investigative Site
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
city: Hong Kong
country: Hong Kong
facility: Novartis Investigative Site
city: Ancona
country: Italy
facility: Novartis Investigative Site
city: Aviano
country: Italy
facility: Novartis Investigative Site
city: Bergamo
country: Italy
facility: Novartis Investigative Site
city: Catanzaro
country: Italy
facility: Novartis Investigative Site
city: Firenze
country: Italy
facility: Novartis Investigative Site
city: Genova
country: Italy
facility: Novartis Investigative Site
city: Meldola
country: Italy
facility: Novartis Investigative Site
city: Modena
country: Italy
facility: Novartis Investigative Site
city: Orbassano Torino
country: Italy
facility: Novartis Investigative Site
city: Perugia
country: Italy
facility: Novartis Investigative Site
city: Torino
country: Italy
facility: Novartis Investigative Site
city: Varese
country: Italy
facility: Novartis Investigative Site
city: Gyeonggi
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Distrito Federal
country: Mexico
facility: Novartis Investigative Site
city: Almere
country: Netherlands
facility: Novartis Investigative Site
city: Arnhem
country: Netherlands
facility: Novartis Investigative Site
city: Den Haag
country: Netherlands
facility: Novartis Investigative Site
city: Ede
country: Netherlands
facility: Novartis Investigative Site
city: Eindhoven
country: Netherlands
facility: Novartis Investigative Site
city: Hoogeveen
country: Netherlands
facility: Novartis Investigative Site
city: Leiden
country: Netherlands
facility: Novartis Investigative Site
city: Nijmegen
country: Netherlands
facility: Novartis Investigative Site
city: Utrecht
country: Netherlands
facility: Novartis Investigative Site
city: Hamilton
country: New Zealand
facility: Novartis Investigative Site
city: Wellington
country: New Zealand
facility: Novartis Investigative Site
city: Jesus Maria
country: Peru
facility: Novartis Investigative Site
city: La Victoria
country: Peru
facility: Novartis Investigative Site
city: Surquillo
country: Peru
facility: Novartis Investigative Site
city: Cebu City
country: Philippines
facility: Novartis Investigative Site
city: Quezon City
country: Philippines
facility: Novartis Investigative Site
city: Coimbra
country: Portugal
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Cordoba
country: Spain
facility: Novartis Investigative Site
city: Gea
country: Spain
facility: Novartis Investigative Site
city: Ibanez
country: Spain
facility: Novartis Investigative Site
city: La Maso
country: Spain
facility: Novartis Investigative Site
city: Villaroel
country: Spain
facility: Novartis Investigative Site
city: Bern
country: Switzerland
facility: Novartis Investigative Site
city: Locarno
country: Switzerland
facility: Novartis Investigative Site
city: Lugano
country: Switzerland
facility: Novartis Investigative Site
city: Chang Hwa
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Khonkaen
country: Thailand
facility: Ratchathew
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
city: Essex
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
city: New Castle Upon Tyne
country: United Kingdom
facility: Novartis Investigative Site
city: Nottingham
country: United Kingdom
facility: Novartis Investigative Site
city: Plymouth
country: United Kingdom
facility: Novartis Investigative Site
city: Sheffield
country: United Kingdom
facility: Novartis Investigative Site
city: Swansea
country: United Kingdom
facility: Novartis Investigative Site
city: Caracas
country: Venezuela
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.