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OpenTrials
Completed

NCT Number: NCT00332709

Safety/Efficacy of Letrozole Monotherapy 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.

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Key information

Conditions

Osteoporosis Bone Diseases Bone Diseases, Metabolic Breast Diseases Breast Neoplasms Metabolic Diseases Musculoskeletal Diseases Neoplasms Neoplasms by Site Nutritional and Metabolic Diseases Postmenopausal Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Novartis Investigative Site, Cologne, Germany

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

letrozole

Drug

2.5 mg/day for 3 years

Zoledronic acid

Drug

4 mg every 6 months

Primary outcomes

  1. Change in Bone Mineral Density (BMD) From Baseline to Month 36

    Time frame: at 36 months as compared to baseline

    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.

  2. Percent Change in Bone Mineral Density (BMD) From Baseline to Month 36

    Time frame: Baseline, 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.

  3. Change in T-score From Baseline to Month 36

    Time frame: Baseline and 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.

  4. Change in Z Score From Baseline to Month 36

    Time frame: Baseline, 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.

Secondary outcomes

  1. Change in Bone Mineral Density From Baseline to 12 Months

    Time frame: Baseline, 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.

  2. Number of Participants With Any Kind of Fractures, by Visit.

    Time frame: Baseline, Month 6, 12, 18, 24 , 30 and 36

    Number of participants with fractures of any type since the last visit

  3. Median Disease Free Survival (DFS)

    Time frame: 36 months

    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.

  4. Change in T-Score From Baseline to Month 12

    Time frame: Baseline, 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.

  5. Change in Z-Score From Baseline to Month 12

    Time frame: Baseline, 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

Sponsors and collaborators

Lead sponsor

Novartis

Industry

Registry information

Official study 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

Important dates

Study start
2006
Primary completion
2010
Study completion
2010
First posted
Jun 2, 2006
Registry last updated
Nov 16, 2011

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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