A Phase 3, Randomized, Double-Blind, Multicenter Trial Comparing Orteronel Plus Prednisone With Placebo Plus Prednisone in Patients With Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,560
- 主要终点
- Radiographic Progression-free Survival (rPFS)
研究概览
简要总结
This is a randomized, double-blind, multicenter, phase 3 study evaluating orteronel (TAK-700) plus prednisone compared with placebo plus prednisone in the treatment of men with progressive, chemotherapy-naive, metastatic, castration-resistant prostate cancer (mCRPC)
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
- Double (Participant, Investigator)
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
- •Each patient must meet all of the following inclusion criteria:
- •Voluntary written consent
- •Male patients 18 years or older
- •Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma
- •Radiograph-documented metastatic disease
- •Progressive disease
- •Prior surgical castration or concurrent use of an agent for medical castration
- •Either absence of pain or pain not requiring use of any opioid or narcotic analgesia in the 2 weeks prior to study entry
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Even if surgically sterilized, patients must practice effective barrier contraception during the entire study treatment and for 4 months after the last dose of study drug, OR abstain from heterosexual intercourse
- •Meet screening laboratory values as specified in protocol
- •Stable medical condition
排除标准
- •Patients meeting any of the following exclusion criteria are not to be enrolled in the study:
- •Known hypersensitivity to orteronel, prednisone or gonadotropin-releasing hormone (GnRH) analogue
- •Received prior therapy with orteronel, aminoglutethimide, ketoconazole or abiraterone
- •Received antiandrogen therapy within 6 weeks for bicalutamide and 4 weeks for all others prior to first dose of study drug
- •Continuous daily use of oral prednisone or oral dexamethasone for more than 14 days within 3 months prior to study
- •Received prior chemotherapy for prostate cancer with exception of neoadjuvant/adjuvant therapy as part of initial primary treatment for local disease that was completed 2 or more years prior to screening
- •Exposure to radioisotope therapy within 4 weeks of receiving first dose of study drug; exposure to external beam radiation within 2 weeks of start of screening until receiving the first dose of study drug
- •Documented central nervous system metastases
- •Treatment with any investigational compound within 30 days prior to first dose of study drug
- •Current spinal cord compression, bilateral hydronephrosis or current bladder neck outlet obstruction
- •Diagnosis or treatment of another malignancy within 2 years preceding first dose of study drug except nonmelanoma skin cancer or in situ malignancy completely resected
- •Uncontrolled cardiovascular condition as specified in study protocol
- •Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C
- •Unwilling or unable to comply with protocol
- •Uncontrolled nausea, vomiting or diarrhea
- •Known gastrointestinal disease or procedure that could interfere with oral absorption or tolerance of orteronel
研究组 & 干预措施
Orteronel + prednisone
干预措施: Orteronel (Drug)
Orteronel + prednisone
干预措施: Prednisone (Drug)
Placebo + prednisone
干预措施: Placebo (Drug)
Placebo + prednisone
干预措施: Prednisone (Drug)
结局指标
主要结局
Radiographic Progression-free Survival (rPFS)
时间窗: Baseline until radiographic disease progression or death, whichever occurred first (approximately up to 4.7 years)
rPFS was defined as the time from randomization to the first objective evidence of radiographic disease progression assessed by independent central radiology review or death due to any cause, whichever occurred first. Radiographic disease progression was evaluated by computerized tomography (CT) scan or magnetic resonance imaging (MRI) and radionuclide bone scans at regularly scheduled visits. Radiographic disease progression in bone required a confirmatory scan. Radiographic disease progression in soft tissue did not require a confirmatory scan for purposes of analysis. Radiographic disease progression was evaluated by independent central radiology review using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for soft tissue disease and Prostate Cancer Working Group (PCWG2) guidelines for bone disease. Participants who did not reach the endpoint were censored at their last assessment.
Overall Survival
时间窗: Baseline until death (up to 4.7 years)
Overall survival was calculated from the date of participant randomization to the date of participant death due to any cause. Participants without documentation of death at time of the analysis were censored as of the date the participant was last known to be alive, or the data cutoff date, whichever was earlier.
次要结局
- Time to Docetaxel Chemotherapy(Baseline until start of docetaxel chemotherapy (up to 4.7 years))
- Time to Subsequent Antineoplastic Therapy(Baseline until start of subsequent antineoplastic therapy (up to 4.7 years))
- Percentage of Participants With Objective Response(Baseline until disease progression or death, whichever occurred first (approximately up to 4.7 years))
- Percentage of Participants Achieving 50 Percent Reduction From Baseline in Prostate Specific Antigen (PSA50) Response at Week 12(Week 12)
- Percentage of Participants With Favorable Circulating Tumor Cell Count (CTC) Levels at Week 12(Week 12)
- Time to Pain Progression(Baseline until End of treatment (EOT) (approximately up to 4.7 years))
- Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(Baseline up to 30 days after last dose of study drug (Cycle 61 Day 58))
- Number of Participants With Treatment-emergent Adverse Events Greater Than or Equal to (>=) Grade 3(Baseline up to 30 days after last dose of study drug (Cycle 61 Day 58))
- Number of Participants With TEAEs Related to Vital Signs(Baseline up to 30 days after last dose of study drug (Cycle 61 Day 58))
- Number of Participants With TEAEs Related to Weight(Baseline up to 30 days after last dose of study drug (Cycle 61 Day 58))
- Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status(Baseline until EOT (approximately up to 4.7 years))
- Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings(Baseline up to EOT (Cycle 61 Day 58))
- Worst Change From Baseline Over Time in Cardiac Ejection Fraction(Baseline up to 30 days or EOT whichever is later (approximately up to Cycle 61 Day 58))
- Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Coagulation(Baseline up to 30 days or EOT whichever is later (approximately up to Cycle 61 Day 58))
- Percentage of Participants With Skeletal Related Events (SRE)(Baseline up to EOT (approximately up to 4.7 years))
- Time to SRE(Baseline up to EOT (Cycle 61 Day 58))
- Percentage of Participants Achieving PSA50 Response at Any Time During the Study(Cycle: 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34 and 37)
- Percentage of Participants Achieving 90 Percent Reduction From Baseline in Prostate Specific Antigen (PSA90 Response) at Week 12(Week 12)
- Percentage of Participants Achieving PSA90 Response at Any Time During the Study(Cycle: 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34 and 37)
- Time to PSA Progression(Baseline until the final on treatment assessment or until end of short term follow-up following discontinuation of treatment, whichever occurred later (approximately up to 4.7 years))
- Time to Deterioration in Global Health Status(Baseline until EOT (approximately up to 4.7 years))