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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00332709
First received: May 31, 2006
Last updated: October 10, 2011
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
Osteoporosis
Postmenopausal
Drug: Letrozole
Drug: Zoledronic acid
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change in Bone Mineral Density (BMD) From Baseline to Month 36 [ Time Frame: at 36 months as compared to baseline ] [ Designated as safety issue: No ]
    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.

  • Percent Change in Bone Mineral Density (BMD) From Baseline to Month 36 [ Time Frame: Baseline, Month 36 ] [ Designated as safety issue: No ]

    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.


  • Change in T-score From Baseline to Month 36 [ Time Frame: Baseline and Month 36 ] [ Designated as safety issue: No ]
    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.

  • Change in Z Score From Baseline to Month 36 [ Time Frame: Baseline, month 36 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change in Bone Mineral Density From Baseline to 12 Months [ Time Frame: Baseline, 12 months ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Any Kind of Fractures, by Visit. [ Time Frame: Baseline, Month 6, 12, 18, 24 , 30 and 36 ] [ Designated as safety issue: No ]
    Number of participants with fractures of any type since the last visit

  • Median Disease Free Survival (DFS) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    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.

  • Change in T-Score From Baseline to Month 12 [ Time Frame: Baseline, Month 12 ] [ Designated as safety issue: No ]
    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.

  • Change in Z-Score From Baseline to Month 12 [ Time Frame: Baseline, Month 12 ] [ Designated as safety issue: No ]
    (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


Enrollment: 83
Study Start Date: January 2006
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Letrozole
Letrozole orally 2.5 mg/day for 3 years
Drug: Letrozole
2.5 mg/day for 3 years
Experimental: Letrozole + Zoledronic Acid
Letrozole orally 2.5mg/day for 3 years; Zoledronic acid 4mg every 6 months by infusion
Drug: Letrozole
2.5 mg/day for 3 years
Drug: Zoledronic acid
4 mg every 6 months

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00332709

Locations
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, Germany
Sponsors and Collaborators
Novartis
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00332709     History of Changes
Other Study ID Numbers: CFEM345DDE09
Study First Received: May 31, 2006
Results First Received: August 11, 2011
Last Updated: October 10, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Novartis:
Breast cancer
postmenopausal
bone mineral density
Zoledronic acid
Letrozole
extended adjuvant treatment.
Postmenopausal women with primary hormone receptor positive breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Osteoporosis
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Letrozole
Zoledronic acid
Diphosphonates
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Bone Density Conservation Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014