An Open-Label, Phase 1/2, Safety, Pharmacokinetic and Proof-of-Concept Study of ARN-509 in Patients With Progressive Advanced Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 127
- 试验地点
- 15
- 主要终点
- Phase 1 and 2: Percentage of Participants With Greater Than or Equal to (>=) 50 Percent (%) Reduction in Prostate-Specific Antigen (PSA) at Week 12
研究概览
简要总结
The purpose of this study is to assess the safety and activity of ARN-509 in men with advanced castration resistant prostate cancer. Patients will first be enrolled into Phase 1 of the study to identify a tolerable dose for the Phase 2 portion of the study. In the Phase 2, 3 different cohorts of patients will be enrolled to evaluate the safety and activity of ARN-509.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •NON-METASTATIC CRPC
- •Inclusion Criteria
- •Histologically or cytologically proven prostate cancer with high risk for development of metastases, defined as either a PSA value >=8 ng/mL within the last 3 months or PSA Doubling Time <=10 months
- •Ongoing androgen depletion therapy with a Gonadotropin Releasing Hormone (GnRH) analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration)
- •Castrate levels of serum testosterone of less than or equal to 50 ng/dL
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- •A life expectancy of at least 3 months
排除标准
- •Distant metastases, including CNS and vertebral or meningeal involvement
- •Prior treatment with MDV3100
- •Prior treatment with abiraterone
- •Prior treatment with ketoconazole
- •Concurrent treatment with medications known to have seizure potential
- •Concurrent treatment with corticosteroids. If they are already on steroids, patients will be allowed to enroll on the study but will need to taper off as soon as possible.
- •QTc > 450 msec
- •History of seizure or condition that may predispose to seizure
- •Evidence of severe or uncontrolled systemic disease or HIV infection
- •METASTATIC CRPC, TREATMENT-NAIVE
- •Inclusion Criteria
- •Histologically or cytologically proven prostate cancer with progressive disease based on either PSA or radiographic progression
- •Ongoing androgen depletion therapy with a Gonadotropin Releasing Hormone (GnRH) analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration)
- •Castrate levels of serum testosterone of less than or equal to 50 ng/dL
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- •A life expectancy of at least 3 months
- •Exclusion Criteria
- •History of, or current metastases in the brain or untreated spinal cord compression
- •Prior treatment with MDV3100
- •Prior treatment with abiraterone
- •Prior treatment with ketoconazole
- •Concurrent treatment with medications known to have seizure potential
- •Concurrent treatment with corticosteroids. If they are already on steroids, patients will be allowed to enroll on the study but will need to taper off as soon as possible.
- •QTc > 450 msec
- •History of seizure or condition that may predispose to seizure
- •Evidence of severe or uncontrolled systemic disease or HIV infection
- •METASTATIC CRPC, CHEMOTHERAPY-NAIVE, POST-ABIRATERONE
- •Inclusion Criteria
- •Histologically or cytologically proven prostate cancer with progressive disease based on either PSA or radiographic progression
- •Ongoing androgen depletion therapy with a Gonadotropin Releasing Hormone (GnRH) analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration)
- •Castrate levels of serum testosterone of less than or equal to 50 ng/dL
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- •A life expectancy of at least 3 months
- •Patients must have received a minimum of 6 months of abiraterone treatment prior to disease progression
- •Exclusion Criteria
- •History of, or current metastases in the brain or untreated spinal cord compression
- •Prior treatment with MDV3100
- •Prior treatment with ketoconazole
- •Concurrent treatment with medications known to have seizure potential
- •Concurrent treatment with corticosteroids. If they are already on steroids, patients will be allowed to enroll on the study but will need to taper off as soon as possible.
- •QTc > 450 msec
- •History of seizure or condition that may predispose to seizure
- •Evidence of severe or uncontrolled systemic disease or HIV infection
研究组 & 干预措施
Dose Escalation Cohort (Phase 1)
ARN-509 will be administered at a starting dose of 30 milligram per day (mg/day), with escalations to 60 mg, 90 mg, 120 mg, 180 mg, 240 mg, 300 mg, 390 mg, and 480 mg daily. Once Recommended Phase 2 Dose (RP2D) has been selected, Phase 1 participants being treated at the lower dose levels will be allowed to escalate to the RP2D level at the discretion of the primary investigator.
干预措施: ARN-509 (Phase 1) (Drug)
Non-metastatic CRPC (Phase 2)
Participants with non-metastatic, treatment-naive Castration-Resistant Prostate Cancer (CRPC) with rapidly rising Prostate Specific Antigen (PSA) will be enrolled. ARN-509 will be administered at Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D), determined in Phase 1.
干预措施: ARN-509 (Phase 2) (Drug)
Treatment-naive metastatic CRPC (Phase 2)
Participants with treatment-naive metastatic CRPC will be enrolled. ARN-509 will be administered at MTD and/or RP2D, determined in Phase 1.
干预措施: ARN-509 (Phase 2) (Drug)
Post-abiraterone metastatic CRPC (Phase 2)
Participants with metastatic CRPC that are chemotherapy-naive, but have been previously treated with abiraterone will be enrolled. ARN-509 will be administered at MTD and/or RP2D, determined in Phase 1.
干预措施: ARN-509 (Phase 2) (Drug)
结局指标
主要结局
Phase 1 and 2: Percentage of Participants With Greater Than or Equal to (>=) 50 Percent (%) Reduction in Prostate-Specific Antigen (PSA) at Week 12
时间窗: Week 12
Percentage of participants with \>=50% decrease in PSA compared to baseline were assessed at Week 12. PSA progression was defined by the protocol-specific Prostate Cancer Working Group 2 (PCWG2) criteria: PSA increase greater than or equal to \[\>=\] 25 percent \[%\] and \>=2 nanogram per milliliter \[ng/mL\] above the nadir confirmed \>=3 weeks later; or \>=25% and \>=2 ng/mL above baseline PSA after 12 weeks.
次要结局
- Phase 1 and 2: Objective Response Rate(Up to approximately 7 years)
- Phase 1 and 2: Median Time to PSA Progression(Up to approximately 7 years)
- Phase 2: Median Metastasis-Free Survival (MFS)(Up to approximately 7 years)
- Phase 1 and 2: Progression-free Survival (PFS)(Up to approximately 7 years)