A Phase I Study of PCUR-101 in Combination With Androgen Directed Therapy in the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 4
- 主要终点
- Occurrence of Dose Limiting Toxicity
研究概览
简要总结
This is an open label, non-randomized, Phase I, dose escalation/dose expansion study in cohorts of patients with metastatic CRPC at Screening. Dose escalation uses a 3+3 design to determine the maximum tolerated dose (MTD). Once the MTD is defined, the dose expansion phase is used to define the recommended phase 2 dose.
详细描述
Dose Escalation Phase: Eligible patients will enter the study and start receiving daily doses of PCUR-101 during Cycle 1. Subsequent dose cohorts will receive the next higher dose of PCUR-101 according to a 3 + 3 design until the MTD is determined. Patients may remain on these treatment cycles if they do not progress or experience any dose limiting toxicities (DLTs).
Dose Expansion Phase: Once the MTD has been determined, approximately 18 patients in 3 cohorts will be enrolled for further evaluations of safety, PK, and preliminary clinical activity during successive 28-day cycles in the dose expansion phase: Expansion Cohort 1 will receive PCUR-101 at the MTD, Expansion Cohort 2 will receive PCUR-101 at one dose level lower than the MTD and dutasteride once daily, and Expansion Cohort 3 (6 patients) will receive PCUR-101 at one dose level lower than the MTD in patients about to start abiraterone (1000 mg QD) and prednisone (5 mg twice daily [BID]) as their standard of care.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Histologically confirmed diagnosis of prostate cancer
- •Demonstrates metastatic CRPC
- •Castrate level of serum testosterone at screening
- •Adequate hematologic, renal, and hepatic function
- •ECOG status ≤1
- •Life expectancy of at least 3 months
- •No more than one prior course of cytotoxic chemotherapy
排除标准
- •Pure small cell, neuroendocrine or other variant (non-adenocarcinoma) prostate cancer histology
- •Visceral metastasis excluding lymph nodes
- •Use of opiate analgesics for prostate cancer pain or non-cancer pain
- •other investigational agents or concurrent anticancer therapy other than standard androgen deprivation therapy within 4 weeks
- •History of bleeding disorder
- •History of seizure disorder
- •Concomitant use of warfarin
- •Prior exposure to PCUR-101
- •History of myocardial infarction, arterial thrombotic events, heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmia
- •Received wide-field external beam radiation therapy within 4 weeks
- •Moderate to severe neuropathy
研究组 & 干预措施
PCUR-101 Dose Escalation
PCUR-101 dosed orally once per day in 28 day cycles. Patients will be enrolled into escalating dose levels during the dose escalation phase
干预措施: PCUR-101 (Drug)
PCUR-101 Dose Expansion Cohort 1
PCUR-101 dosed orally once per day in 28 day cycles
干预措施: PCUR-101 (Drug)
PCUR-101 Dose Expansion Cohort 2
PCUR-101 in combination with dutasteride dosed orally once per day in 28 day cycles
干预措施: PCUR-101 (Drug)
PCUR-101 Dose Expansion Cohort 2
PCUR-101 in combination with dutasteride dosed orally once per day in 28 day cycles
干预措施: Dutasteride 0.5 mg (Drug)
PCUR-101 Dose Expansion Cohort 3
PCUR-101 dosed orally once per day in combination with abiraterone (once per day) and prednisone (twice per day) in 28 day cycles
干预措施: PCUR-101 (Drug)
PCUR-101 Dose Expansion Cohort 3
PCUR-101 dosed orally once per day in combination with abiraterone (once per day) and prednisone (twice per day) in 28 day cycles
干预措施: Abiraterone and Prednisone (Drug)
结局指标
主要结局
Occurrence of Dose Limiting Toxicity
时间窗: over the first 28 days of dosing
Incidence of Adverse Adverse Events
次要结局
- Determination of pharmacokinetic parameters - Cmax(over the first 28 days of dosing)
- Preliminary Evidence of efficacy/anti tumor activity - RECIST(through study completion, average of 12 months)
- Determination of pharmacokinetic parameters - Tmax(over the first 28 days of dosing)
- Determination of pharmacokinetic parameters - T1/2(over the first 28 days of dosing)
- Preliminary Evidence of efficacy/anti tumor activity - PSA levels(through study completion, average of 12 months)