A Randomised, Double-Blind, Placebo-Controlled, Multi-Centre Phase 3 Study to Determine the Treatment Effect of Denosumab in Subjects With Non-Metastatic Breast Cancer Receiving Aromatase Inhibitor Therapy.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 3,420
- 试验地点
- 1
- 主要终点
- Time to First Clinical Fracture
研究概览
简要总结
The purpose of this study is to determine whether denosumab compared to placebo, will reduce the rate of first clinical fracture in women with non-metastatic breast cancer receiving (non-steroidal) aromatase inhibitor therapy.
详细描述
Participants will remain on treatment until the required number of events (where an event is defined as first clinical fracture) is reached and all participants have had the opportunity to receive a minimum of at least 2 doses of study drug, whichever occurs later. The primary analysis data cut-off date (PADCD) is defined as the time at which the required number of events is reached and all participants have had the opportunity to receive at least 2 doses of study drug. When the PADCD is reached, all participants will discontinue study drug.
Following the study PADCD, participants will be followed every 12 months starting from their last study visit until a maximum of 66 months after PADCD.
After approval of Amendment 4, willing and eligible participants randomized to placebo during the double-blind phase may participate in an open-label phase (OLP) and receive denosumab 60 mg Q6M for up to 36 months (maximum of 7 doses).
After approval of Amendment 6 in 2019 a zoledronic acid (ZA) substudy was added to the protocol. Willing and eligible participants who participated in the OLP of the study and completed open-label denosumab may opt in to this ZA substudy and either receive a single dose of ZA (Therapy Arm), or be managed according to the current standard of care for this patient population (Control Arm).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 45 Years 至 100 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Denosumab
Participants received 60 mg denosumab subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.
干预措施: Denosumab (Biological)
Denosumab
Participants received 60 mg denosumab subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.
干预措施: Non-steroidal aromatase inhibitor therapy (Drug)
Placebo
Participants received placebo subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.
干预措施: Placebo (Drug)
Placebo
Participants received placebo subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.
干预措施: Non-steroidal aromatase inhibitor therapy (Drug)
SubStudy: Zoledronic Acid
Eligible participants who completed the open-label phase could be enrolled into the zoledronic acid substudy and randomized to receive a single 5 mg intravenous dose of zoledronic acid 8 months after the last open-label dose of denosumab.
干预措施: Zoledronic Acid (Drug)
Substudy: Standard of Care
Eligible participants who completed the open-label phase could be enrolled into the zoledronic acid substudy and randomized to receive standard of care 8 months after the last open-label dose of denosumab.
干预措施: Standard of Care (Other)
结局指标
主要结局
Time to First Clinical Fracture
时间窗: From randomization until the primary analysis cut-off date of 26 March 2014; maximum time on main study at the cut-off was 87 months
The time to first on-study clinical fracture was defined as the number of days from randomization to the date of the x-ray confirming the clinical fracture. A clinical fracture is any clinically evident fracture with associated symptoms and confirmed by x-ray. Participants who died or withdrew without experiencing a clinical fracture were censored at the date of last contact or study termination whichever was earlier.
次要结局
- Percent Change From Baseline in Total Hip BMD at Month 36 at Pre-selected Sites(Baseline and Month 36)
- Percent Change From Baseline in Femoral Neck BMD at Month 36 at Pre-selected Sites(Baseline and Month 36)
- Percent Change From Baseline in Total Lumbar Spine Bone Mineral Density (BMD) at Month 36 at Pre-selected Sites(Baseline and Month 36)
- Overall Survival (OS)(Randomization until end of main study, maximum duration of main study was 152 months)
- Number of Participants With New Vertebral Fractures(36 months)
- Number of Participants With New or Worsening Vertebral Fractures(36 months)
- Disease-free Survival (DFS)(From randomization until the DFS data cut-off date of 15 September 2015; maximum time on main study at the cut-off was 102 months)
- Bone Metastases-free Survival (BMFS)(From randomization until end of main study, maximum time on main study was 152 months)