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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

May 31, 2006
October 10, 2011
January 2006
August 2010   (final data collection date for primary outcome measure)
  • 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.
Treatment difference in change in BMD measured by DXA in lumbar spine (L1-L4) at 36 months as compared to baseline.
Complete list of historical versions of study NCT00332709 on ClinicalTrials.gov Archive Site
  • 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
BMD (measured by DXA at lumbar spine, L1-L4), at 12 months, Fracture rate during treatment and in Follow up, Disease free survival (DFS)
Not Provided
Not Provided
 
Safety/Efficacy of Letrozole Monotherapy or in Combination With Zoledronic Acid as Extended Adjuvant Treatment of Postmenopausal Patients With Primary Breast Cancer
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

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Osteoporosis
  • Postmenopausal
  • Drug: Letrozole
    2.5 mg/day for 3 years
  • Drug: Zoledronic acid
    4 mg every 6 months
  • Experimental: Letrozole
    Letrozole orally 2.5 mg/day for 3 years
    Intervention: Drug: Letrozole
  • Experimental: Letrozole + Zoledronic Acid
    Letrozole orally 2.5mg/day for 3 years; Zoledronic acid 4mg every 6 months by infusion
    Interventions:
    • Drug: Letrozole
    • Drug: Zoledronic acid
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
83
August 2010
August 2010   (final data collection date for primary outcome measure)

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.

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT00332709
CFEM345DDE09
Not Provided
Novartis
Novartis
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
October 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP