Safety Study to Determine the Maximum Tolerated Dose, Pharmacokinetics and Pharmacodynamics of Oral MP470, a Multitargeted Tyrosine Kinase Inhibitor, in Patients With Solid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 4
- 主要终点
- Safety and tolerability
研究概览
简要总结
Multicenter, open-label, dose-ranging study in two parts: maximum tolerated dose (MTD) segment (the first 28-day course of MP 470) followed by long-term safety segment.
MTD segment: follows standard oncology phase-I design; within-patient dose level adjustments prohibited; each patient participates in one of three stages:
- Accelerated Titration Stage
- Dose Escalation/De-Escalation Stage
- Dose Confirmation Stage
详细描述
Multicenter, open-label, dose-ranging study in two parts: MTD Segment (the first 28-day course of MP 470) followed by Long-Term Safety Segment
MTD Segment: follows standard oncology phase-I design; within-patient dose level adjustments prohibited; each patient participates in one of three stages:
Accelerated Titration Stage: 1 patient per dose level; first patient receives MP 470 at 100 mg/day; subsequent patients assigned higher dose levels based on modified Fibonacci sequence; stage stops when any first-course DLT is observed or when grade-2 or greater MP 470-related toxicity is observed at 2 dose levels; dosing next patient prohibited until previous patient's MTD-Segment result is confirmed Dose Escalation/De-Escalation Stage: 3 patients per cohort; two additional patients enrolled to receive last dose level studied during Accelerated Titration Stage (first 3-patient cohort); subsequent 3-patient cohorts assigned dose level conditional on number of patients with first-course DLT in previous cohort; new cohorts enrolled until MTD is defined; dosing next cohort prohibited until previous cohort's MTD-Segment results are confirmed Dose Confirmation Stage: an additional 6-10 patients enrolled to receive MP 470 at the established MTD; patient accrual stops following Dose Confirmation Long-Term Safety Segment: patients continue receiving 28-day courses of MP 470 until experiencing unmanageable toxicity or disease progression; within-patient dose level adjustments based on toxicity; DLT during preceding 28-day course mandates one-level dose reduction; one-level dose increase possible in absence of grade-3 or greater MP 470-related AEs during preceding 28-day course
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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient has a histological or cytological diagnosis of unresectable or metastatic solid-tumor cancer that is refractory to standard therapies or for which no standard therapy exists. Patients with refractory lymphoma (Hodgkin's or NHL) are also permitted to participate.
- •The patient must read, understand and sign the IRB-approved informed consent form (ICF) confirming his or her willingness to participate in this trial.
- •The patient is willing and able to participate in all of the required evaluations and procedures described in this study protocol, including swallowing MP 470 capsules.
- •The patient is at least 18 years old.
- •The patient is capable of fasting for 6 hours.
- •The patient has Karnofsky Performance Status ≥ 70 (see Appendix 5).
- •The patient has adequate bone marrow function evidenced, at minimum, by Hgb ≥ 9 g/dL, ANC ≥ 1.5 x 109/L and platelet count ≥ 100 x 109/L.
- •The patient has normal renal and hepatic function evidenced, at minimum, by total serum bilirubin ≤ 2 mg/dL; AST and ALT ≤ 2.5 x ULN (upper limit of normal for the clinical laboratory), but ≤ 5 x ULN is acceptable if due to hepatic metastases; serum albumin ≥ 2 g/dL; and serum creatinine ≤ 2 mg/dL.
- •The patient has normal cardiac function in the opinion of the investigator and supported by left ventricular ejection fraction (LVEF) 50% or greater on the screening echocardiogram, no significant abnormalities on the screening ECG (eg, left bundle branch block, III degree AV block, acute myocardial infarction or QTc interval > 450 msec) and no history of additional risk factors for torsade de pointes (eg, heart failure, hypokalemia or family history of Long QT Syndrome).
- •The patient has recuperated from any prior surgical procedures including at least 4 weeks rest since a major surgery.
- •The patient does not have childbearing potential or has had a negative serum pregnancy test within the past 14 days.
- •The patient does not have reproductive potential or has agreed to use and will use an approved method of contraception during the study and for 3 months following the last dose of MP
- •The patient is not lactating.
排除标准
- •The patient has a life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of oral MP 470, or put the study outcomes at risk.
- •The patient has any serious, uncontrolled active infection that requires systemic treatment.
- •The patient has a history of significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure and/or myocardial infarction.
- •The patient has received any anticancer agent(s) within the past 3 weeks, including investigational agents, chemotherapy (6 weeks for nitrosoureas or mitomycin), immunotherapy, biologic or hormonal therapy other than LHRH agonists.
- •The patient has received radiation therapy within the past 4 weeks.
- •The patient has a grade-2 or more severe toxicity (other than alopecia) continuing from prior anticancer therapy.
- •The patient has active CNS metastases (primary brain tumors are permitted).
- •The patient requires treatment with immunosuppressive agents other than corticosteroids that have been at stable doses for at least 2 weeks.
结局指标
主要结局
Safety and tolerability
时间窗: 6 months
次要结局
未报告次要终点