Phase I Clinical Trial to Assess the Safety and Pharmacokinetic Profile of CKD-516 Inj. Administered on A Twice-Weekly Schedule in Patients With Advanced Solid Cancers Failed to Standard Therapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- MTD, Maximum Tolerated Dose
研究概览
简要总结
A phase I study is conducted to determine the maximum tolerated dose (MTD), dose limiting toxicity (DLT), safety and pharmacokinetics (PK) profile of a single agent CKD-516 injection on twice-weekly schedule in patients with advanced solid cancers failed to standard therapy. The usefulness of the this regimen is evaluated by response rate, progression free survival and vascular disruption effect by Dynamic Contrast-Enhanced MRI (DCE-MRI) or DWI.
详细描述
This is an open label, dose escalation study. Patients receive CKD-516 IV over 30 minutes on day 1, 4, 8, 11 every 3 weeks in the absence of unacceptable toxicity or disease progression. Cohorts of 3~6 patients receive escalating doses of CKD-516 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicity.
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
- 20 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •20~75 years
- •Histologically or cytologically confirmed solid tumors that have failed to standard therapy or for which no life prolonging treatment exists
- •ECOG PS 0-2
- •Life expectancy 12 weeks
- •Hematopoietic: ANC ≥ 1,500/mm3, Platelet ≥ 100,000/mm3, Hemoglobin ≥ 9.0g/dL, Prothrombin time, Activated partial thromboplastin time: normal range
- •Hepatic: total bilirubin ≤ 1.5×ULN(except Gilbert's syndrome patients), AST, ALT ≤ 3.0×ULN(AST, ALT ≤ 5.0×ULN in case of liver metastases)
- •serum creatinine ≤ 1.5×ULN or Creatinine clearance ≥ 60 mL/min
- •PT, APTT: normal range
- •Signed a written informed consent
排除标准
- •Brain or Leptomeningeal metastases
- •History of Ischemic heart disease(e.g., myocardial infarction, unstable angina pectoris) or Clinically significant heart disease such as NYHA Class III and IV Congestive atrial arrhythmias, within 6 months prior to first dose of study drug
- •Stable angina pectoris shown symptoms within 6 months prior to first dose of study durg, or Clinically significant abnormality on EKG or echocardiogram(e.g., LVEF < 50% or clinically significant heart wall abnormality or heart muscle damage)
- •Cerebrovascular disease such as stroke
- •Grade 2 or greater motor or sensory peripheral neuropathy
- •Uncontrolled hypertension(greater than 150 mmHg systolic or 100 mmHg diastolic regardless of medication)
- •acute infection or blooding tendencies that would preclude study compliance
- •Serious vascular disease such as Aortic aneurysm
- •Other psychiatric disorders or other conditions that would preclude study compliance
- •Receiving anticoagulation with warfarin, heparin, etc.
- •Receiving antitumor therapy(surgery, immunotherapy or chemotherapy) within 3 weeks prior to first dose of study drug(6 weeks for nitrosoureas and mitomycin C, 2 weeks for radiation therapy)
- •Other concurrent antitumor therapy
- •Patients with serious hypersensitivity history or allergy to CKD-516
- •Pregnant or nursing, active serum pregnancy test. Fertile patients must use effective contraception
- •Participation in a clinical trial within 4 weeks of first dose of study drug
- •Patients judged to be inappropriate for this study by the investigator with other reasons
研究组 & 干预措施
CKD-516 inj.
CKD-516 Inj, 3.3~13mg/m2/day, D1, 4, 8, 11 every 3 weeks
干预措施: CKD-516 inj. (Drug)
结局指标
主要结局
MTD, Maximum Tolerated Dose
时间窗: up to 21days
次要结局
- Vascular disruption effect(4hr, 24hr post-dose)
- ORR%, Objective response rate(up to 42weeks)
- PK parameter of CKD-516(0(Pre-dose), 24hrs post dose (Day 1), 0, 0.5, 4, 8, 24hours post-dose(Day 11))
- DLT, Dose-limiting Toxicity(up to 21days)