A Phase II Randomized, Double-blind, Placebo-controlled Trial of Radium-223 Dichloride in Combination With Exemestane and Everolimus Versus Placebo in Combination With Exemestane and Everolimus When Administered to Metastatic HER2 Negative Hormone Receptor Positive Breast Cancer Subjects With Bone Metastases
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 283
- 主要终点
- Symptomatic Skeletal Event-free Survival (SSE-FS)
研究概览
简要总结
The objective of this study is to assess efficacy and safety of radium 223 dichloride in subjects with human epidermal growth factor receptor 2 (HER2) negative hormone receptor positive breast cancer with bone metastases treated with exemestane and everolimus
After implementation of CSP Amendment 10, only a limited number of subjects will remain in this study, in order to reduce the burden to study subjects, collection of data will be reduced and will focus mainly on acute safety, SSE, and OS. Once subjects are rolled over, the long-term safety will be collected and assessed entirely in the separate extended safety follow-up study.
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
- •Women (≥18 years of age) with metastatic breast cancer not amenable to curative treatment by surgery or radiotherapy.
- •Documentation of histological or cytological confirmation of estrogen receptor positive (ER+) and HER2 negative adenocarcinoma of the breast must be available.
- •Documentation of menopausal status: postmenopausal subjects or pre-menopausal subjects with ovarian radiation or concomitant therapy with a luteinizing hormone-releasing hormone (LH-RH) agonist/antagonist are eligible.
- •Subjects with bone dominant disease with at least 2 skeletal metastases identified at baseline by bone scintigraphy and confirmed by computed tomography (CT)/magnetic resonance imaging (MRI).
- •Subjects must have received at least one line of hormonal therapy in the metastatic setting.
- •Subjects who are eligible as per the Investigator's assessment and according to the local label for treatment with exemestane and everolimus as a second line or greater of hormone therapy in a metastatic setting.
- •Subjects must have experienced recurrent/progressive disease following treatment with a non-steroidal aromatase inhibitor (letrozole or anastrozole) in an adjuvant or metastatic setting
- •Subjects must have experienced no more than two skeletal-related events (SREs) prior to study entry defined as: need for external beam radiotherapy (EBRT) to bone pain, 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 bisphosphonates or denosumab 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.
- •Patients with immediately life-threatening visceral disease for whom chemotherapy is preferred treatment option.
- •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 provided it was administered at least 1 year prior to study entry.
- •Subjects who received prior treatment or are already receiving everolimus treatment prior to study entry are not eligible.
- •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.
研究组 & 干预措施
Radium-223 dichloride + exemestane/everolimus
Up to 6 cycles of radium-223 dichloride 50kBq/kg body weight (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) (randomized). Participants will also receive exemestane, 25-mg tablet once daily (after a meal), and everolimus, 10 mg once daily (with or without food), and supportive care as per the local or institutional standard of practice.
干预措施: Radium-223 dichloride (Xofigo, BAY88-8223) (Drug)
Radium-223 dichloride + exemestane/everolimus
Up to 6 cycles of radium-223 dichloride 50kBq/kg body weight (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) (randomized). Participants will also receive exemestane, 25-mg tablet once daily (after a meal), and everolimus, 10 mg once daily (with or without food), and supportive care as per the local or institutional standard of practice.
干预措施: Exemestane (Drug)
Radium-223 dichloride + exemestane/everolimus
Up to 6 cycles of radium-223 dichloride 50kBq/kg body weight (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) (randomized). Participants will also receive exemestane, 25-mg tablet once daily (after a meal), and everolimus, 10 mg once daily (with or without food), and supportive care as per the local or institutional standard of practice.
干预措施: Everolimus (Drug)
Placebo + exemestane/everolimus
Up to 6 cycles of saline injection (placebo) (randomized). Participants will also receive exemestane, 25-mg tablet once daily (after a meal), and everolimus, 10 mg once daily (with or without food), and supportive care as per the local or institutional standard of practice.
干预措施: Placebo (saline) (Drug)
Placebo + exemestane/everolimus
Up to 6 cycles of saline injection (placebo) (randomized). Participants will also receive exemestane, 25-mg tablet once daily (after a meal), and everolimus, 10 mg once daily (with or without food), and supportive care as per the local or institutional standard of practice.
干预措施: Exemestane (Drug)
Placebo + exemestane/everolimus
Up to 6 cycles of saline injection (placebo) (randomized). Participants will also receive exemestane, 25-mg tablet once daily (after a meal), and everolimus, 10 mg once daily (with or without food), and supportive care as per the local or institutional standard of practice.
干预措施: Everolimus (Drug)
结局指标
主要结局
Symptomatic Skeletal Event-free Survival (SSE-FS)
时间窗: Up to 55 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. Per Protocol Amendment 10, following primary analysis completion, further assessments were focused on safety, and only limited efficacy data including SSE and survival were collected and not designed to support reconsideration of the primary analysis efficacy conclusions. Accordingly, no formal statistical analyses were performed for primary and secondary efficacy outcomes in the final analysis. All primary and secondary efficacy outcome measures presented in this document came from the primary completion analysis.
次要结局
- Time to Opiate Use for Cancer Pain(Up to 55 months)
- Percentage of Participants With Pain Improvement(Up to 55 months)
- Overall Survival(Up to 55 months)
- Time to Pain Progression(Up to 55 months)
- Number of Participants With Hematological Toxicities: Worst Grade Under Treatment(From first dosing up to 30 days after the last administration of study treatments, up to 72.6 months)
- Time to Cytotoxic Chemotherapy(Up to 55 months)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(From first dosing up to 30 days after the last administration of study treatments, up to 72.6 months)
- Number of Participants With Post-treatment Chemotherapy Related Adverse Events(From post-treatment till end of study, up to 45.8 months)
- Number of Participants With New Primary Malignancies(From first dosing till end of study, up to 72.6 months)
- Radiological Progression-free Survival (rPFS)(Up to 55 months)