A Phase II Randomized, Double-blind, Placebo-controlled Trial of Radium-223 Dichloride Versus Placebo When Administered to Metastatic HER2 Negative Hormone Receptor Positive Breast Cancer Subjects With Bone Metastases Treated With Hormonal Treatment Background Therapy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Bayer
- 入组人数
- 99
- 主要终点
- Symptomatic Skeletal Event Free Survival (SSE-FS)
研究概览
简要总结
The objective of this study was to assess efficacy and safety of radium-223 dichloride in subjects with human epidermal growth factor receptor 2 negative (HER2 negative) hormone receptor positive breast cancer with bone metastases treated with hormonal treatment background therapy
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Documentation of histological or cytological confirmation of estrogen receptor positive (ER+) and HER2 negative adenocarcinoma of the breast must be available.
- •Women (≥18 years of age) with metastatic breast cancer not amenable to curative treatment by surgery or radiotherapy.
- •Documentation of menopausal status: post menopausal or premenopausal subjects are eligible.
- •Subjects with bone dominant disease with at least 2 skeletal metastases identified at baseline by bone scintigraphy and confirmed by CT/magnetic resonance imaging (MRI). Presence of metastases in soft tissue (skin, subcutaneous, muscle, fat, lymph nodes)and/or visceral metastases is allowed.
- •Measurable or non-measurable disease (but radiologically evaluable) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
- •Subjects must have received at least one line of hormonal therapy in the metastatic setting
- •Subjects who are eligible for further standard of care endocrine treatment.
- •Subjects enrolled in the current study must start treatment with the single hormone agent either within 15 days prior to randomization or after randomization (before or simultaneously to the first injection of Ra-223/placebo).
- •Subjects must have experienced no more than two skeletal-related events (SREs) prior to study entry defined as: Need for external beam radiotherapy (EBRT) tor bone, pathological bone fracture (excluding major trauma), spinal cord compression and/or orthopedic surgical procedure. Subjects with no prior SREs are not permitted.
- •Subjects must be on therapy with bisphosphonate and denosumab. and are required to have been on such therapy for at least 1 month before start of study treatment.
- •Adequate hematological, liver and kidney function.
排除标准
- •Subjects with Inflammatory breast cancer.
- •Subjects who have either received chemotherapy for metastatic disease or are considered by the treating investigator to be appropriate candidates for chemotherapy as current treatment for metastatic breast cancer are excluded. Chemotherapy administered for adjuvant/neo adjuvant disease is acceptable.
- •Subjects with known or history of brain metastases or leptomeningeal disease: subjects with neurological symptoms must undergo a contrast CT scan or MRI of the brain within 28 days prior to randomization to exclude active brain metastasis. Imaging of the central nervous system (CNS) is otherwise not required.
- •Known presence of osteonecrosis of jaw.
- •Patients with immediately life-threatening visceral disease, for whom chemotherapy is the preferred treatment option.
- •Lymphangitic carcinomatosis.
- •Patients with ascites requiring paracentesis within 2 weeks prior to study entry (signature of informed consent) and during the screening period.
研究组 & 干预措施
Radium 223 dichloride
Participants treated with a single hormonal agent as background therapy received 50 kBq/kg body weight (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) of Radium 223 dichloride intravenously for a maximum of 6 cycles at intervals of 4 weeks
干预措施: Radium-223 dichloride (Xofigo, BAY88-8223) (Drug)
Radium 223 dichloride
Participants treated with a single hormonal agent as background therapy received 50 kBq/kg body weight (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) of Radium 223 dichloride intravenously for a maximum of 6 cycles at intervals of 4 weeks
干预措施: Background hormonal therapy (Other)
Placebo
Participants treated with a single hormonal agent as background therapy received isotonic saline (0.9% sodium chloride solution for injection) intravenously for a maximum of 6 cycles at intervals of 4 weeks
干预措施: Placebo (saline) (Drug)
Placebo
Participants treated with a single hormonal agent as background therapy received isotonic saline (0.9% sodium chloride solution for injection) intravenously for a maximum of 6 cycles at intervals of 4 weeks
干预措施: Background hormonal therapy (Other)
结局指标
主要结局
Symptomatic Skeletal Event Free Survival (SSE-FS)
时间窗: Up to approximately 51 months
Time from date of randomization to occurrence of one of the following, whichever happened earlier: 1) an on study SSE, which was defined as the use of external beam radiotherapy (EBRT) to relieve skeletal symptoms, the occurrence of new symptomatic pathological bone fractures (vertebral or nonvertebral), the occurrence of spinal cord compression, a tumor related orthopedic surgical intervention; or 2) death from any cause
次要结局
- Time to Pain Progression(Up to approximately 51 months)
- Time to Cytotoxic Chemotherapy(Up to approximately 51 months)
- Number of Participants With Treatment-emergent Adverse Events(Up to approximately 7 months)
- Overall Survival(Up to approximately 51 months)
- Radiological Progression-free Survival (rPFS)(Up to approximately 51 months)
- Number of Participants With Post-treatment Adverse Events Including Additional Malignancies and Chemotherapy Related Adverse Events(From 30 days after the last dose of study treatment until the end of study, assessed up to approximately 44 months)
- Time to Opiate Use for Cancer Pain(Up to approximately 51 months)
- Pain Improvement Rate(Up to approximately 51 months)