A Multi-center, Open-label, Dose-escalation Study to Assess the Pharmacokinetics of ASA404 in Adult Cancer Patients With Impaired Hepatic Function and With Normal Hepatic Function
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 2
- 主要终点
- (Core Phase)To evaluate the PK of a single intravenous dose (900, 1200 and 1800 mg/m2) of ASA404 in adult cancer patients with impaired hepatic function compared to matching patients with normal hepatic function
研究概览
简要总结
This study is designed to obtain pharmacokinetic data following a single-dose 20-minute i.v. administration of ASA404 (900, 1200, or 1800 mg/m2) in adult cancer patients with varying degrees of hepatic impairment. The study will be carried out in cancer volunteer patients (utilizing controls with normal hepatic function) who will be assigned to four hepatic impairment groups according to their pre-dose (Day-1) and total bilirubin level. The study will consist of two phases, a (Core Phase) that will evaluate the pharmacokinetics of a single i.v. dose (900, 1200 and 1800 mg/m2) of ASA404 in adult cancer patients with impaired hepatic function, and compared to controls with normal hepatic function. The assessments will be done on the safety and tolerability of that single dose in adult cancer patients with impaired hepatic function and compared to controls with normal hepatic function. The Extension Phase will consist of assessing the safety and tolerability of ASA404 at the same three doses in combination with a sponsor-approved taxane-based regimen in adult cancer patients with impaired hepatic function and compared to controls with normal hepatic function.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- All
- 接受健康志愿者
- 否
入选标准
- •Patients having histologically-proven solid tumors, who are refractory to standard chemotherapy;
- •Patients whom chemotherapy with an investigational agent in combination with docetaxel, or paclitaxel + carboplatin is appropriate;
- •Age ≥ 18 years old
- •Creatinine clearance according to Cockcroft-Gault formula ≥ 60 mL/min
- •A minimum of 4 weeks must have elapsed since the last treatment with other cancer therapies;
- •Potassium, calcium, magnesium and phosphorus values within the normal range Total bilirubin ≤ 6 X ULN
排除标准
- •Patients having CNS metastases, must have a CT or MRI of the brain performed to rule out CNS metastases;
- •Patients with leptomeningeal disease metastases;
- •Major surgery </ 4 weeks prior to the start of study;
- •Prior exposure to VDAs or other vascular targeting agents;
- •Right bundle branch block (RBBB), complete left bundle branch block (LBBB);
- •Administration of CYP1A2 and CYP3A4/5 enzyme inducing or inhibiting drugs within 14 days prior to starting study drug;
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
ASA404 + standard therpy
干预措施: ASA404 (Drug)
结局指标
主要结局
(Core Phase)To evaluate the PK of a single intravenous dose (900, 1200 and 1800 mg/m2) of ASA404 in adult cancer patients with impaired hepatic function compared to matching patients with normal hepatic function
时间窗: 18 months
次要结局
- To assess the safety and tolerability of a single i.v. dose (900, 1200 and 1800 mg/m2) of ASA404 in adult cancer patients with impaired hepatic function as compared to controls with normal hepatic function(18 months)
- (Extension Phase) assess the safety & tolerability of ASA404 either alone or in combination with a sponsor approved taxane-based regimen in adult cancer patients with impaired hepatic function as compared to controls with normal hepatic function(18 months)
- To assess the safety of the combined regimen on the frequency and severity of adverse events and the number of laboratory values worsening from baseline based on the CTCAE grade assessment.(18 months)