A PHASE 1, OPEN-LABEL, DOSE-ESCALATION SAFETY AND PHARMACOKINETIC STUDY OF MDV3100 IN PATIENTS WITH CASTRATION-RESISTANT PROSTATE CANCER
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 140
- 试验地点
- 9
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)
研究概览
简要总结
This is a multi-center open-label dose-escalation study of a novel compound (MDV3100) to treat patients with castration-resistant (hormone-refractory) prostate cancer. Additional patients will be enrolled in expanded cohorts at doses determined to be tolerable. Patients who tolerate the drug and do not progress will be allowed to continue to look for PSA response.
详细描述
This is a Phase 1, open-label, uncontrolled, dose-escalation study with dose-expansion at doses determined to be tolerated. Patients who tolerate the drug and do not progress will be allowed to continue treatment. The study endpoints are safety and tolerability and pharmacokinetics. PSA values will also be collected to look for PSA response.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed adenocarcinoma of the prostate;
- •Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration);
- •Progressive disease after medical or surgical castration,
排除标准
- •Metastases in the brain or active epidural disease. (Note: patients with treated epidural disease are allowed);
研究组 & 干预措施
1
MDV3100
干预措施: MDV3100 (Drug)
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)
时间窗: Baseline up to 30 days after last dose of study treatment (approximately maximum of 129 months)
An adverse events (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both SAEs and non-SAEs.
Percentage of Participants With at Least 1 Dose-limiting Toxicity (DLT): Multiple Dose Period
时间窗: Baseline up to first 35 days of the study treatment in multiple dose period
DLT was defined as a national cancer institute's common toxicity criteria for adverse events (NCI-CTCAE) version 3.0 grade 3 or greater toxicity regardless of perceived causality that is not improved by the use of adequate/maximal medical intervention. Grade 3 alopecia, fever without neutropenia, nausea, vomiting, fatigue, and self-limited or medically controllable adverse events were not considered as DLTs.
Maximum Tolerated Dose (MTD) of MDV3100: Multiple Dose Period
时间窗: Baseline up to first 35 days of the study treatment in multiple dose period
Tolerability was defined as if less than (\<) 4/12 in participants with no prior exposure to MDV3100 (chemo-naive) and \< 4/12 prior chemotherapy participants experienced a DLT within the first 35 days of the multiple dose period. For doses higher than 360 mg/day, tolerability was defined if \<8/24 participants previously treated with chemotherapy experience a DLT within the first 35 days of the multiple dose period. MTD was defined as a dose below the intolerable dose.
次要结局
- Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Single Dose Period(Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period)
- Apparent Volume of Distribution (V/F) of MDV3100: Single Dose Period(Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period)
- Apparent Total Plasma Clearance (CL/F) of MDV3100: Single Dose Period(Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period)
- Maximum Plasma Concentration (Cmax) of MDV3100: Single Dose Period(Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period)
- Apparent Terminal Elimination Half-Life (T1/2) of MDV3100: Single Dose Period(Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period)
- Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of MDV3100: Single Dose Period(Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period)
- Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose (AUC[0-24]) of MDV3100: Multiple Dose Period(Pre-dose, 0.5, 1, 2, 24 hours post dose on Day 84 of Multiple Dose Period)
- Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Multiple Dose Period(Pre-dose, 0.5, 1, 2, 24 hours post dose on Day 84 of Multiple Dose Period)
- Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC[0-t]) of MDV3100: Single Dose Period(Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours postdose on Day 1 of Single Dose Period)
- Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose (AUC[0-24]) of MDV3100: Single Dose Period(Pre-dose, 0.5, 1, 2, 4, 6, 24 hours post dose on Day 1 of Single Dose Period)
- Maximum Plasma Concentration (Cmax) of MDV3100: Multiple Dose Period(Pre-dose, 0.5, 1, 2, 24 hours post dose on Day 84 of Multiple Dose Period)
- Minimum Observed Plasma Concentration (Cmin) of MDV3100: Multiple Dose Period(Pre-dose on Day 1 of Multiple Dose Period)
- Apparent Total Plasma Clearance (CL/F) of MDV3100: Multiple Dose Period(Pre-dose, 0.5, 1, 2, 24 hours post dose on Day 84 of Multiple Dose Period)