Safety/Efficacy of Letrozole Monotherapy or in Combination With Zoledronic Acid as Extended Adjuvant Treatment of Postmenopausal Patients With Primary Breast Cancer

Osteoporosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00332709
• Other study ID #: CFEM345DDE09
• Status: Completed
• Phase: Phase 3
• First received: May 31, 2006
• Last updated: October 10, 2011
• Start date: January 2006
• Est. completion date: August 2010

Study information

• Verified date: October 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: August 2010
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Osteoporosis
• Postmenopausal

Intervention

Drug:
• Letrozole
2.5 mg/day for 3 years
• Zoledronic acid
4 mg every 6 months

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Deggendorf
Germany	Novartis Investigative Site	Frankfurt/Main
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Georgsmarienhutte
Germany	Novartis Investigative Site	Gottingen
Germany	Novartis Investigative Site	Halle
Germany	Novaertis Investigative Site	Hamein
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Hoxter
Germany	Novartis Investigative Site	Ilsede
Germany	Novartis Investigative Site	Jena
Germany	Novartis Investigative Site	Karlsruhe
Germany	Novartis Investigative Site	Koln
Germany	Novartis Investigative Site	Leer
Germany	Novartis Investigative Site	Lubeck
Germany	Novartis Investigative Site	Mannheim
Germany	Novartis Investigative Site	Munster
Germany	Novartis Investigative Site	Rostock
Germany	Novartis Investigative Site	Salzgitter
Germany	Novartis Investigative Site	Schwenningen
Germany	Novartis Investigative Site	Stendal
Germany	Novartis Investigative Site	Volklingen
Germany	Novartis Investigative Site	Witten

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	Change in Bone Mineral Density From Baseline to 12 Months	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.	Baseline, 12 months	No
Secondary	Number of Participants With Any Kind of Fractures, by Visit.	Number of participants with fractures of any type since the last visit	Baseline, Month 6, 12, 18, 24 , 30 and 36	No
Secondary	Median Disease Free Survival (DFS)	Disease Free Survival is measured in days and represents the number of days participants were progression free. Progression free survival is defined as the time from randomization to the date of the first documented progression or recurrence of disease or death from any cause. Median disease free survival is the time when 50% of the patients had a recurrence.	36 months	No
Secondary	Change in T-Score From Baseline to Month 12	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, Month 12	No
Secondary	Change in Z-Score From Baseline to Month 12	(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 12	No