A Phase III Randomized, Double-blind, Placebo-controlled Trial of Radium-223 Dichloride in Combination With Abiraterone Acetate and Prednisone/Prednisolone in the Treatment of Asymptomatic or Mildly Symptomatic Chemotherapy-naïve Subjects With Bone Predominant Metastatic Castration-resistant Prostate Cancer(CRPC)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 806
- 主要终点
- Symptomatic Skeletal Event Free Survival (SSE-FS)
研究概览
简要总结
To determine if the addition of radium-223 dichloride to standard treatment is able to prolong life and to delay events specific for prostate cancer which has spread to the bone, such as painful fractures or bone pain which needs to be treated with an X-ray machine.
详细描述
This study is a phase III multinational, multicenter,randomized, double blind, placebo controlled, study with a randomization allocation ratio of 1:1 (radium-223 dichloride plus abiraterone acetate plus prednisone/prednisolone: placebo plus abiraterone acetate plus prednisone/prednisolone). Until the final overall survival (OS) analysis, the study period consisted of screening / randomization, treatment, active follow-up with clinic visits, active follow-up without clinic visits, and longterm follow-up phases. Up until this point, subjects received study treatment (radium-223 dichloride or placebo in addition to abiraterone acetate plus prednisone / prednisolone for the first 6 cycles followed by abiraterone acetate plus prednisone / prednisolone thereafter) until an on-study SSE occurred (or other withdrawal criteria were met). After the final OS analysis (after implementation of Amendment 7), in order to reduce the burden to study subjects, evaluation of efficacy and exploratory endpoints will be discontinued, except for symptomatic skeletal event (SSE) and OS. Subjects who are discontinued from study treatment will initiate the long-term follow-up period; therefore, active follow-up periods will no longer be applicable. Subjects who are in active follow-up at the time of Amendment 7 is implemented should have the end of active follow-up completed (protocol driven decision) and should be directly transitioned into the extended safety follow-up study. Long term follow-up will continue until the subject dies, is lost to follow-up, withdraws informed consent, actively objects to collection of further data , or is transitioned to the extended safety follow-up study. Subjects will be followed for safety for up to 7 years, which eventually will be completed in this study or in the 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
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed adenocarcinoma of the prostate
- •Male subjects of age ≥ 18 years
- •Prostate cancer progression documented by prostate specific antigen (PSA) according to the Prostate Cancer Working Group 2 (PCWG2) criteria or radiological progression according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1
- •Two or more bone metastases on bone scan within 4 weeks prior to randomization with no lung, liver, other visceral and/or brain metastasis
- •Asymptomatic or mildly symptomatic prostate cancer
- •Subjects who received combined androgen blockade with an anti-androgen must have shown PSA progression after discontinuing the anti-androgen prior to enrollment
- •Maintenance of medical castration or surgical castration with testosterone less than 50 ng/dL (1.7nmol/L)
- •Eastern Cooperative Oncology Group performance status (ECOG PS) score 0 or 1
排除标准
- •Prior cytotoxic chemotherapy for the treatment of CRPC, including taxanes, mitoxantrone and estramustine
- •Any chronic medical condition requiring a higher dose of corticosteroid than 5 mg prednisone/prednisolone twice daily
- •Pathological finding consistent with small cell carcinoma of the prostate
- •History of visceral metastasis, or presence of visceral metastasis detected by screening imaging examinations
- •History of or known brain metastasis
- •Malignant lymphadenopathy exceeding 3 cm in short-axis diameter
- •Blood transfusion or erythropoietin stimulating agents prior 4 weeks of screening and during the whole screening period before randomization
- •Imminent spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI). Subjects with history of spinal cord compression should have completely recovered
- •Use of opiate analgesics for cancer-related pain, including codeine and dextropropoxyphene, currently or anytime during the 4- week period prior to randomization.
研究组 & 干预措施
Radium-223 dichloride + Abi/Pred
Participants received 6 intravenous (IV) administrations of radium-223 dichloride 50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) body weight at intervals of 4 weeks, along with oral abiraterone acetate tablets 1000 milligrams (mg) every day plus prednisone/prednisolone 5 mg twice daily (abi/pred) for 6 cycles, followed by abi/pred until an on-study symptomatic skeletal event (SSE) occurred (or other withdrawal criteria were met)
干预措施: Abiraterone (Drug)
Radium-223 dichloride + Abi/Pred
Participants received 6 intravenous (IV) administrations of radium-223 dichloride 50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) body weight at intervals of 4 weeks, along with oral abiraterone acetate tablets 1000 milligrams (mg) every day plus prednisone/prednisolone 5 mg twice daily (abi/pred) for 6 cycles, followed by abi/pred until an on-study symptomatic skeletal event (SSE) occurred (or other withdrawal criteria were met)
干预措施: Radium-223 dichloride (Xofigo, BAY88-8223) (Drug)
Radium-223 dichloride + Abi/Pred
Participants received 6 intravenous (IV) administrations of radium-223 dichloride 50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) body weight at intervals of 4 weeks, along with oral abiraterone acetate tablets 1000 milligrams (mg) every day plus prednisone/prednisolone 5 mg twice daily (abi/pred) for 6 cycles, followed by abi/pred until an on-study symptomatic skeletal event (SSE) occurred (or other withdrawal criteria were met)
干预措施: Prednisone/Prednisolone (Drug)
Placebo + Abi/Pred
Participants received 6 IV administrations of placebo matched to radium-223 dichloride at intervals of 4 weeks, along with abi/pred for 6 cycles, followed by abi/pred until an on-study SSE occurred (or other withdrawal criteria were met)
干预措施: Matching placebo (normal saline) (Drug)
Placebo + Abi/Pred
Participants received 6 IV administrations of placebo matched to radium-223 dichloride at intervals of 4 weeks, along with abi/pred for 6 cycles, followed by abi/pred until an on-study SSE occurred (or other withdrawal criteria were met)
干预措施: Abiraterone (Drug)
Placebo + Abi/Pred
Participants received 6 IV administrations of placebo matched to radium-223 dichloride at intervals of 4 weeks, along with abi/pred for 6 cycles, followed by abi/pred until an on-study SSE occurred (or other withdrawal criteria were met)
干预措施: Prednisone/Prednisolone (Drug)
结局指标
主要结局
Symptomatic Skeletal Event Free Survival (SSE-FS)
时间窗: From randomization until first onset of on-study symptomatic skeletal event (SSE) or death, up to 47 months
SSE-FS was defined as time (months) from randomization to the earliest of onset date of skeletal symptoms treated with external beam radiotherapy (EBRT), onset date of pathological bone fracture, onset date of spinal cord compression, procedure date of tumor-related orthopedic surgery, or death from any cause. Participants who died without prior SSE and ≥ 13 weeks after the last SSE assessment are censored at the last SSE assessment date. Participants alive at the survival cut-off date are censored at the last date known to be alive. Participants with multiple events are only counted for the category in which the first event occurred. If multiple SSE (component events) occur on the same date for 1 participant, the participant is only counted into 1 category in the order of: spinal cord compression \> bone fracture \> orthopedic surgery \> EBRT.
次要结局
- Overall Survival (OS)(From randomization until death from any cause, up to 67 months)
- Radiological Progression Free Survival (rPFS)(From randomization until the date of confirmed radiological progression or death, up to 47 months)
- Time to Pain Progression(From randomization until the date of pain progression based on pain score, up to 47 months)
- Time to Cytotoxic Chemotherapy(From randomization until the date of first cytotoxic chemotherapy, up to 47 months)
- Time to Opiate Use for Cancer Pain(From randomization until the date of opiate use, up to 47 months)
- Number of Participants With Treatment-emergent Adverse Events(From start of study treatment until the end of the treatment period, up to 110 months)
- Number of Participants With Radium-223/Placebo-related Treatment-emergent Adverse Events Per Maximum Intensity(From start of study treatment until the end of the treatment period, up to 110 months)
- Number of Participants With Any Treatment-emergent Additional Primary Malignancies(From start of study treatment until the end of the treatment period, up to 110 months)
- Number of Participants With Treatment-emergent Bone Fractures(From start of study treatment until the end of the treatment period, up to 110 months)
- Number of Participants With Post-treatment Adverse Events(After the treatment period, up to 48.5 months in active follow-up and 74.9 months in long-term follow-up)
- Number of Participants With Any Study Drug-related Post-treatment Adverse Events Per Maximum Intensity(After the treatment period, up to 48.5 months in active follow-up and 74.9 months in long-term follow-up)
- Number of Participants With Post-treatment Additional Primary Malignancies(After the treatment period, up to 48.5 months in active follow-up and 74.9 months in long-term follow-up)
- Number of Participants With Post-treatment Chemotherapy-related Blood and Lymphatic System Disorders(After the treatment period, up to 48.5 months in active follow-up and 74.9 months in long-term follow-up)
- Number of Participants With Post-treatment Bone Fractures(After the treatment period, up to 48.5 months in active follow-up and 74.9 months in long-term follow-up)