A Three Arm Randomized, Open-label Phase II Study of Radium-223 Dichloride 50 kBq/kg (55 kBq/kg After Implementation of NIST Update) Versus 80 kBq/kg (88 kBq/kg After Implementation of NIST Update), and Versus 50 kBq/kg (55 kBq/kg After Implementation of NIST Update) in an Extended Dosing Schedule in Subjects With Castration-resistant Prostate Cancer Metastatic to the Bone
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 391
- 试验地点
- 5
- 主要终点
- Number of Participants With an Event Defining SSE Free Survival - High Dose vs. Standard Dose
研究概览
简要总结
This study will assess different doses and regimens of radium-223 dichloride on the incidence of symptomatic skeletal events. Eligible subjects must have castration resistant prostate cancer with 2 or more skeletal metastases documented within 8 weeks of randomization. Subjects will be randomized to one of 3 treatment arms in a 1:1:1 fashion: a standard regimen of radium-223 dichloride of 50 kBq/kg (55 kBq/kg after implementation of NIST update) injections every month for 6 months, a high dose regimen of 80 kBq/kg (88 kBq/kg after implementation of NIST update)injections every month for 6 months or an extended duration regimen of 50 kBq/kg (55 kBq/kg after implementation of NIST update) injections every month for 12 months. Following the treatment phase, subjects will be followed up every 12 weeks for a minimum of 2 years, at which point they will enter a long term follow-up period during which they are seen every 6 months for up to 7 years after the last dose of radium dichloride. Symptomatic skeletal event and safety endpoints will be assessed at each clinic visit. Pain and analgesic use data will be collected every 4 weeks through Week 48. Additionally, radiological assessments including MRI/CT of the abdomen and pelvis and chest CT, as well as technetium-99 bone scans will be performed at Weeks 8, 16, and 24 and continue every 12 weeks thereafter until disease progression is documented in either the bone or in soft tissue. Radiological imaging will be evaluated by blinded central review.
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
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed adenocarcinoma of the prostate
- •Castration-resistant disease defined as:
- •Serum testosterone level: ≤ 50 ng/dL (1.7 nmol/L)
- •Bilateral orchiectomy or maintenance on androgen ablation therapy with luteinizing-hormone-releasing hormone (LHRH) agonist or antagonist, or polyestradiol phosphate
- •Serum PSA (Prostate specific antigen) progression defined as 2 subsequent increases in PSA over a previous reference value (a minimum of 2 ng/mL [μg/L]) OR
- •Radiographic evidence of disease progression in bone (according to Prostate Cancer Clinical Trials Working Group 2 [PCWG2] criteria) with or without PSA progression
- •Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to
- •In case of ECOG PS 2, the PS has to be due to metastatic prostate cancer to the bone.
- •Two or more skeletal metastases (≥ 2 hot spots) on bone scintigraphy within 8 weeks of randomization
排除标准
- •History of visceral metastasis, or visceral metastases
- •Lymphadenopathy with lymph nodes exceeding 3 cm in short axis diameter
- •Central nervous system (CNS) metastases
- •Treatment with cytotoxic chemotherapy for prostate cancer within the previous 4 weeks prior to randomization, or planned treatment with cytotoxic chemotherapy agents for prostate cancer during the treatment period or follow-up
- •Chronic conditions associated with non-malignant abnormal bone growth (e.g. confirmed Paget's disease of bone)
- •Prior treatment with radium-223 dichloride
- •Prior systemic radiotherapy and hemibody external radiotherapy
研究组 & 干预措施
Radium-223 dichloride (Standard dose)
One injection to be administered every 4 weeks up to 6 injections. The dose per injection is 50 kBq/kg body weight (55 kBq/kg after implementation of NIST update).
干预措施: Radium-223 dichloride (Xofigo, BAY88-8223) (Drug)
Radium-223 dichloride (High dose)
One injection to be administered every 4 weeks up to 6 injections. The dose per injection is 80 kBq/kg body weight (88 kBq/kg after implementation of NIST update).
干预措施: Radium-223 dichloride (Xofigo, BAY88-8223) (Drug)
Radium-223 dichloride (Extended standard dose)
One injection to be administered every 4 weeks up to 12 injections. The dose per injection is 50 kBq/kg body weight (55 kBq/kg after implementation of NIST update).
干预措施: Radium-223 dichloride (Xofigo, BAY88-8223) (Drug)
结局指标
主要结局
Number of Participants With an Event Defining SSE Free Survival - High Dose vs. Standard Dose
时间窗: From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization)
Symptomatic skeletal event (SSE) free survival is based on the following events: 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, and death. In this evaluation - comparison 1, SSE-FS following randomization is defined in ITT participants as the time from randomization to an SSE or death, whichever occurs first.
Symptomatic Skeletal Event-Free Survival - High Dose vs. Standard Dose
时间窗: From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization)
In this evaluation - comparison 1, SSE-FS following randomization is defined in ITT participants as the time from randomization to an SSE or death, whichever occurs first.
Number of Participants With an Event Defining SSE Free Survival - Extended Dose vs. Standard Dose
时间窗: From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization)
Symptomatic skeletal event (SSE) free survival is based on the following events: 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, and death. In this evaluation - Comparison 2, SSE-FS from 6th dose is defined in W24 participants as the time from Week 24 baseline (the 6th dose date) to an SSE or death, whichever occurs first.
Symptomatic Skeletal Event-Free Survival - Extended Dose vs. Standard Dose
时间窗: From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization)
In this evaluation - Comparison 2, SSE-FS from 6th dose is defined in W24 participants as the time from Week 24 baseline (the 6th dose date) to an SSE or death, whichever occurs first.
Number of Participants With an Event Defining SSE Free Survival - Three Dose Groups As Randomized
时间窗: From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization)
Symptomatic skeletal event (SSE) free survival is based on the following events: 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, and death.
Symptomatic Skeletal Event Free Survival - Three Dose Groups As Randomized
时间窗: From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization)
Symptomatic skeletal event (SSE) is defined as follows: 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.
次要结局
- Number of Participants With an Overall Survival Event - High Dose vs. Standard Dose(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Overall Survival - High Dose vs. Standard Dose(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Number of Participants With First Symptomatic Skeletal Event - High Dose vs. Standard Dose(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Time to First Symptomatic Skeletal Event - High Dose vs. Standard Dose(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Number of Participants With an Overall Survival Event - Extended Dose vs. Standard Dose(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Number of Participants With First Symptomatic Skeletal Event - Extended Dose vs. Standard Dose(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Overall Survival - Extended Dose vs. Standard Dose(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Number of Participants With an Overall Survival - Three Dose Groups As Randomized(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Overall Survival Event - Three Dose Groups as Randomized(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Time to First Symptomatic Skeletal Event - Extended Dose vs. Standard Dose(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Time to Radiological Progression - Extended Dose vs. Standard Dose(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Number of Participants With a Radiological Progression Event - Three Dose Groups as Randomized(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Timepoint Pain Improvement Rate - Three Dose Groups as Randomized(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Number of Participants With a Pain Progression Event - Extended Dose vs. Standard Dose(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Number of Participants With First Symptomatic Skeletal Event - Three Dose Groups as Randomized(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Time to First Symptomatic Skeletal Event - Three Dose Groups as Randomized(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Number of Participants With a Radiological Progression Event-Free - Extended Dose vs. Standard Dose(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Number of Participants With a Radiological Progression Event-Free - High Dose vs. Standard Dose(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Radiological Progression Free Survival - High Dose vs. Standard Dose(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Radiological Progression Free Survival - Extended Dose vs. Standard Dose(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Number of Participants With a Radiological Progression Event-Free - Three Dose Groups as Randomized(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Radiological Progression Free Survival - Three Dose Groups as Randomized(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Time to Radiological Progression - Three Dose Groups as Randomized(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Timepoint Pain Improvement Rate - Extended Dose vs. Standard Dose(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Number of Participants With a Radiological Progression Event - High Dose vs. Standard Dose(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Time to Radiological Progression - High Dose vs. Standard Dose(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Time to Pain Progression - High Dose vs. Standard Dose(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Time to Pain Progression - Extended Dose vs. Standard Dose(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Number of Participants With a Radiological Progression Event - Extended Dose vs. Standard Dose(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Number of Participants With a Pain Progression Event - High Dose vs. Standard Dose(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Number of Participants With a Pain Progression Event - Three Dose Groups as Randomized(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Time to Pain Progression - Three Dose Groups as Randomized(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))
- Number of Participants With Treatment-Emergent Adverse Events(From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization))