Clinical trial NCT00332709: Safety/Efficacy of Letrozole Monotherapy or in Combination With Zoledronic Acid as Extended Adjuvant Treatment of Postmenopausal Patients With Primary Breast Cancer
Official title: An Open Phase III Trial With Letrozole Alone or in Combination With Zoledronic Acid as Extended Adjuvant Treatment of Postmenopausal Patients With Primary Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteoporosis
Postmenopausal
Keywords: Breast cancer
postmenopausal
bone mineral density
Zoledronic acid
Letrozole
extended adjuvant treatment.
Postmenopausal women with primary hormone receptor positive breast cancer
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2006-06-02
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Additional protocol defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Change in Bone Mineral Density (BMD) From Baseline to Month 36
timeFrame: at 36 months as compared to baseline
measure: Percent Change in Bone Mineral Density (BMD) From Baseline to Month 36
timeFrame: Baseline, Month 36
measure: Change in T-score From Baseline to Month 36
timeFrame: Baseline and Month 36
measure: Change in Z Score From Baseline to Month 36
timeFrame: Baseline, month 36
Secondary outcomes:
measure: Change in Bone Mineral Density From Baseline to 12 Months
timeFrame: Baseline, 12 months
measure: Number of Participants With Any Kind of Fractures, by Visit.
timeFrame: Baseline, Month 6, 12, 18, 24 , 30 and 36
measure: Median Disease Free Survival (DFS)
timeFrame: 36 months
measure: Change in T-Score From Baseline to Month 12
timeFrame: Baseline, Month 12
measure: Change in Z-Score From Baseline to Month 12
timeFrame: Baseline, Month 12
Other outcomes:
Locations:
city: Deggendorf
country: Germany
facility: Novartis Investigative Site
city: Frankfurt/Main
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Georgsmarienhutte
country: Germany
facility: Novartis Investigative Site
city: Gottingen
country: Germany
facility: Novartis Investigative Site
city: Halle
country: Germany
facility: Novartis Investigative Site
city: Hamein
country: Germany
facility: Novaertis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Hoxter
country: Germany
facility: Novartis Investigative Site
city: Ilsede
country: Germany
facility: Novartis Investigative Site
city: Jena
country: Germany
facility: Novartis Investigative Site
city: Karlsruhe
country: Germany
facility: Novartis Investigative Site
city: Koln
country: Germany
facility: Novartis Investigative Site
city: Leer
country: Germany
facility: Novartis Investigative Site
city: Lubeck
country: Germany
facility: Novartis Investigative Site
city: Mannheim
country: Germany
facility: Novartis Investigative Site
city: Munster
country: Germany
facility: Novartis Investigative Site
city: Rostock
country: Germany
facility: Novartis Investigative Site
city: Salzgitter
country: Germany
facility: Novartis Investigative Site
city: Schwenningen
country: Germany
facility: Novartis Investigative Site
city: Stendal
country: Germany
facility: Novartis Investigative Site
city: Volklingen
country: Germany
facility: Novartis Investigative Site
city: Witten
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: