A Double-blind, Randomised, Multiple Dose, Phase III, Multicentre Study of Alpharadin in the Treatment of Patients With Symptomatic Hormone Refractory Prostate Cancer With Skeletal Metastases
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 921
- 试验地点
- 134
- 主要终点
- Overall Survival
研究概览
简要总结
ALSYMPCA (ALpharadin in SYMPtomatic Prostate CAncer) is an international Phase III clinical study to evaluate the efficacy and safety of Radium-223 dichloride in patients with hormone refractory prostate cancer and skeletal metastases.
详细描述
The aim of the study was to compare, in patients with symptomatic hormone refractory prostate cancer (HRPC) and skeletal metastases, the efficacy of best standard of care plus Radium-223 dichloride versus best standard of care plus placebo, with the primary efficacy endpoint being overall survival (OS).
Patients were randomised in a 2:1 allocation ratio (Radium-223 dichloride:Placebo). The study treatment consisted of 6 intravenous administrations of Radium-223 dichloride or placebo (saline) each separated by an interval of 4 weeks. The patient were followed until 3 years after first study drug administration.
Within the U.S., the trial was conducted under an IND sponsored by Bayer HealthCare Pharmaceuticals.
All patients received BSoC (Best Standard of Care).
This study has the original PCD as 14 October 2010, when a total of 316 deaths had been observed; this resulted in the Independent Data Monitoring Committee's (IDMC's) recommendation to stop the study as the primary efficacy analysis of overall survival had crossed the pre-specified boundary for efficacy. Later an updated analysis of primary endpoint in the first addendum was done with cut-off of 15 July 2011.
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 or cytologically confirmed adenocarcinoma of the prostate
- •Known hormone refractory disease
- •Multiple skeletal metastases (≥ 2 hot spots) on bone scintigraphy
- •No intention to use cytotoxic chemotherapy within the next 6 months
- •Either regular (not occasional) analgesic medication use for cancer related bone pain or treatment with EBRT (External Beam Radiation Therapy) for bone pain
排除标准
- •Treatment with an investigational drug within previous 4 weeks, or planned during the treatment period
- •Eligible for first course of docetaxel, i.e. patients who are fit enough, willing and where docetaxel is available
- •Treatment with cytotoxic chemotherapy within previous 4 weeks, or planned during the treatment period, or failure to recover from adverse events due to cytotoxic chemotherapy administered more than 4 weeks ago
- •Systemic radiotherapy with strontium-89, samarium-153, rhenium-186 or rhenium-188 for the treatment of bony metastases within previous 24 weeks
- •Other malignancy treated within the last 5 years (except non-melanoma skin cancer or low-grade superficial bladder cancer)
- •History of visceral metastasis, or visceral metastases as assessed by abdominal/pelvic CT or chest x-ray within previous 8 weeks
研究组 & 干预措施
Radium-223 dichloride (Xofigo, BAY88-8223)
Participants received radium-223 50 kilo Becquerel (kBq)/kg body weight (b.w.) for 6 intravenous (IV) administrations separated by 4 weeks intervals plus Best Standard of Care (BSoC).
干预措施: Radium-223 dichloride (Xofigo, BAY88-8223) (Drug)
Radium-223 dichloride (Xofigo, BAY88-8223)
Participants received radium-223 50 kilo Becquerel (kBq)/kg body weight (b.w.) for 6 intravenous (IV) administrations separated by 4 weeks intervals plus Best Standard of Care (BSoC).
干预措施: Best standard of care (BSoC) (Drug)
Placebo
Participants received isotonic saline for 6 IV administrations separated by 4 weeks intervals plus Best Standard of Care (BSoC).
干预措施: Placebo (Drug)
Placebo
Participants received isotonic saline for 6 IV administrations separated by 4 weeks intervals plus Best Standard of Care (BSoC).
干预措施: Best standard of care (BSoC) (Drug)
结局指标
主要结局
Overall Survival
时间窗: From randomization to death due to any cause until approximately 3 years after start of enrollment, the data was collected up to the second data analysis date (15 JUL 2011)
Overall survival was defined as the time from date of randomization to the date of death.
次要结局
- Percentage of Participants With Total ALP Response at Week 12(At Baseline and Week 12)
- Percentage of Participants With Total ALP Response at End of Treatment (EOT; Week 24 or at the Time the Patient Dies or Discontinues Treatment Phase)(At Baseline and End of Treatment (Week 24 or at the time the patient dies or discontinues treatment phase))
- Percentage Change From Baseline in Total ALP at Week 12(At Baseline and Week 12)
- Maximum Percentage Decrease From Baseline in Total ALP During the 24 Week Treatment(From baseline During the 24 Week Treatment)
- Percentage of Participants With PSA Response at EOT (Week 24 or at the Time the Patient Dies or Discontinues Treatment Phase)(At Baseline and End of Treatment (Week 24 or at the time the patient dies or discontinues treatment phase))
- Time to Total Alkaline Phosphatase (ALP) Progression(From randomization to first ALP progression until approximately 3 years after start of enrollment)
- Percentage Change From Baseline in PSA at Week 12(At Baseline and Week 12)
- Percentage of Participants With Total ALP Normalization at Week 12(At Baseline and Week 12)
- Maximum Percentage Decrease From Baseline in Total ALP up to Week 12(From baseline to Week 12)
- Percentage Change From Baseline in PSA at EOT (Week 24 or at the Time the Patient Dies or Discontinues Treatment Phase)(At Baseline and End of Treatment (Week 24 or at the time the patient dies or discontinues treatment phase))
- Time to Occurrence of First Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) by at Least 2 Points From Baseline(From randomization to first deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) until approximately 3 years after start of enrollment)
- Percentage Change From Baseline in Total ALP at EOT (Week 24 or at the Time the Patient Dies or Discontinues Treatment Phase)(At Baseline and End of Treatment (Week 24 or at the time the patient dies or discontinues treatment phase))
- Time to Prostate Specific Antigen (PSA) Progression(From randomization to first PSA progression until approximately 3 years after start of enrollment)
- Percentage of Participants With PSA Response at Week 12(At Baseline and Week 12)
- Maximum Percentage Decrease From Baseline in PSA up to Week 12(From baseline up to Week 12)
- Time to First Skeletal Related Event (SRE)(From randomization to first first SRE until approximately 3 years after start of enrollment)
- Time to Occurrence of First New Symptomatic Pathological Bone Fractures, Vertebral and Non-vertebral(From randomization to occurrence of first new symptomatic pathological bone fractures until approximately 3 years after start of enrollment)
- Time to Occurrence of First Use of External Beam Radiation Therapy (EBRT) to Relieve Skeletal Symptoms(From randomization to first EBRT until approximately 3 years after start of enrollment)
- Time to Occurrence of First Use of Radioisotopes to Relieve Skeletal Symptoms(From randomization to first use of radioisotopes until approximately 3 years after start of enrollment)
- Time to Occurrence of First Tumor Related Orthopedic Surgical Intervention(From randomization to occurrence of first tumor related orthopedic surgical intervention until approximately 3 years after start of enrollment)
- Maximum Percentage Decrease From Baseline in PSA Response During the 24 Week Treatment Period(From baseline to End of Treatment (Week 24; 4 weeks post last injection))
- Time to Occurrence of First Spinal Cord Compression(From randomization to first spinal cord compression until approximately 3 years after start of enrollment)
- Time to Occurrence of First Start of Any Other Anti-cancer Treatment(From randomization to first start of any other anti-cancer treatment until approximately 3 years after start of enrollment)