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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Novartis
- 入组人数
- 83
- 试验地点
- 2
- 主要终点
- Change in T-score From Baseline to Month 36
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Letrozole
Letrozole orally 2.5 mg/day for 3 years
干预措施: Letrozole (Drug)
Letrozole + Zoledronic Acid
Letrozole orally 2.5mg/day for 3 years; Zoledronic acid 4mg every 6 months by infusion
干预措施: Letrozole (Drug)
Letrozole + Zoledronic Acid
Letrozole orally 2.5mg/day for 3 years; Zoledronic acid 4mg every 6 months by infusion
干预措施: Zoledronic acid (Drug)
结局指标
主要结局
Change in T-score From Baseline to Month 36
时间窗: 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.
Change in Bone Mineral Density (BMD) From Baseline to Month 36
时间窗: 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.
Percent Change in Bone Mineral Density (BMD) From Baseline to Month 36
时间窗: 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.
Change in Z Score From Baseline to Month 36
时间窗: 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.
次要结局
- Change in T-Score From Baseline to Month 12(Baseline, Month 12)
- Change in Bone Mineral Density From Baseline to 12 Months(Baseline, 12 months)
- Number of Participants With Any Kind of Fractures, by Visit.(Baseline, Month 6, 12, 18, 24 , 30 and 36)
- Median Disease Free Survival (DFS)(36 months)
- Change in Z-Score From Baseline to Month 12(Baseline, Month 12)