A Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of NOV120401 (CKD-516 Tablet) in Patients With Advanced Refractory Solid Tumors
试验速览
- 阶段
- 1 期
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Safety and MTD/recommended phase 2 dose (RP2D) determination (Number of Participants with Adverse Events)
研究概览
简要总结
The purpose of this open-label, dose-escalation phase I trial is to evaluate the safety, tolerability and pharmacokinetic profiles and to assess the efficacy of NOV120401 (CKD-516 Tablet), a novel vascular disrupting agent, in patients with advanced refractory solid tumors.
详细描述
Vascular disrupting agents are expected to kill cancer cells located in core of tumor tissues by disrupting microvascular structure of tumor. To assess the safety and tolerability of NOV120401 (CKD-516 Tablet), patients with advanced refractory solid tumors will be enrolled in this study. Initial dose of NOV120401 (CKD-516 Tablet) is 5 mg/day, which will be escalated until at least 2 of 6 subjects show dose-limiting toxicities (DLTs). Pharmacokinetic profiles and efficacy by tumor response and vascular disrupting activities will also be assessed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients aged 19 years or older
- •Patients who failed existing anti-cancer therapies
- •ECOG performance status ≤ 2
- •Life expectancy of ≥ 12 weeks
- •Adequate hematological, hepatic and renal functions:
- •Patients who give written informed consent voluntarily
排除标准
- •Prior systemic chemo-, radiochemo-, radio-, immuno-, hormonal and/or biological therapy within 2 weeks before study participation (in case of nitrosoureas and/or mitomycin, within 6 weeks before study participation)
- •Patients who received major surgery within 4 weeks before study participation (in case of VATS and/or ONC surgery, within 2 weeks before study participation)
- •Symptomatic CNS metastases (patients with radiologically and neurologically stable metastases and being off corticosteroids for at least 4 weeks are able to participate in this trial.)
- •NYHA class III or IV heart failure, uncontrolled hypertension (SBP/DBP > 140/90 mm Hg), other clinically significant cardiovascular abnormalities at investigator's discretion (e.g., LVEF < 50%, clinically significant cardiac wall abnormalities or cardiac muscle damages)
- •Acute coronary syndrome (unstable angina or myocardial infarction) within 6 months
- •Uncontrolled arrhythmia
- •Significant cerebrovascular diseases including stroke within 6 months
- •Significant vascular diseases including aortic aneurysm requiring treatment or peripheral arterial diseases
- •Patients with known active hepatitis, HIV infection, or other uncontrolled infectious disease
- •Patients who cannot receive IP by mouth and have a history of clinically significant gastrointestinal disorders which can impede administration, transit or absorption of the IP
- •A history of severe drug hypersensitivity or hypersensitivity to analogs of the IP
- •Pregnancy or breast-feeding
- •Women of childbearing potential (WOCBP) or men who are unwilling to use adequate contraception or be abstinent during the trial and for at least 2 months after the end of treatment
- •Patients who received other investigational products or used other investigational devices within 3 weeks before participation
- •Patients who cannot participate in this trial by investigator's discretion
研究组 & 干预措施
NOV120401 (CKD-516 Tablet)
5 to 45 mg/day PO for 5 consecutive days and 2 days off
干预措施: NOV120401 (Drug)
结局指标
主要结局
Safety and MTD/recommended phase 2 dose (RP2D) determination (Number of Participants with Adverse Events)
时间窗: By 40 weeks after enrollment of the last subject
Number of Participants with Adverse Events
次要结局
- Tumor response(up to 36 weeks)
- Pharmacokinetic profiles (Cmax, Tmax, AUClast, AUCinf, t1/2, CL, MRT, Ctrough) of CKD-516 and S516 (active metabolite of CKD-516)(21 days)
- Vascular disrupting activity measured by tubulin status (western blot from peripheral blood mononuclear cell)(21 days)
- Vascular disrupting activity measured by plasma factor (VEGF, G-CSF, GM-CSF, SDF-1) concentration from serum(21 days)