A Phase I/II Study of PXD101 in Patients With Unresectable Hepatocellular Carcinoma With Pharmacokinetic and Pharmacodynamic Evaluation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 2
- 主要终点
- Dose-limiting Toxicities (DLT) and Maximum Tolerated Dose (MTD) of Belinostat in Patients With Inoperable HCC (Phase I)
研究概览
简要总结
This phase I/II trial is studying the side effects and best dose of belinostat and to see how well it works in treating patients with liver cancer that cannot be removed by surgery. Belinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth
详细描述
PRIMARY OBJECTIVES:
I. Determine the dose-limiting toxicity (DLT) and establish the maximum tolerated dose (MTD) of PXD101 (belinostat) in patients with unresectable hepatocellular carcinoma (HCC). (Phase I) II. Assess the pharmacokinetic profiles of PXD101 in these patients. (Phase I) III. Assess tumor response in patients treated with this drug. (Phase II)
OUTLINE: This is a multicenter, dose-escalation phase I study followed by a phase II study.
PHASE I: Patients receive belinostat intravenously (IV) over 30 minutes on days 1-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of belinostat 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.
PHASE II: Patients receive belinostat (as in phase I) at the MTD determined in phase I.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed hepatocellular carcinoma that is not amenable to curative resection
- •Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques OR as ≥ 10 mm with MRI or spiral CT scan
- •No known brain metastases
- •No clinical ascites or encephalopathy
- •Life expectancy > 12 weeks
- •ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
- •WBC ≥ 3,000/mm³
- •Absolute neutrophil count ≥ 1,500/mm³
- •Platelet count ≥ 100,000/mm³
- •Bilirubin ≤ 1.7 mg/dL
- •Albumin ≥ 2.8 mg/dL
- •ALT ≤ 5.0 times upper limit of normal (ULN)
- •Alkaline phosphatase ≤ 6 times ULN
- •Prothrombin time ≤ 4 sec above ULN
- •Creatinine ≤ 1.6 mg/dL
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients use effective contraception
- •No Child's-Pugh's grading Class C hepatic impairment
- •No history of allergic reaction attributed to compounds of similar chemical or biologic composition to PXD101
- •No marked baseline prolongation of QT/QTc interval, including the following:
- •Repeated demonstration of a QTc interval > 500 msec
- •Long QT Syndrome
- •No ongoing or active infection
- •No significant cardiovascular disease, including any of the following:
- •Unstable angina pectoris
- •Uncontrolled hypertension
- •Congestive heart failure related to primary cardiac disease
- •Condition requiring anti-arrhythmic therapy
- •Ischemic or severe valvular heart disease
- •Myocardial infarction within the past 6 months
- •No psychiatric illness or social situation that would preclude study compliance
- •No other uncontrolled illness
- •More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
- •More than 4 weeks since prior radiotherapy and recovered
- •At least 2 weeks since prior valproic acid
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •No concurrent participation in another investigational study
- •No other concurrent investigational agents
- •No other concurrent anticancer therapy
- •No concurrent use of any of the following:
- •Disopyramide
- •Dofetilide
- •Ibutilide
- •Procainamide
- •Quinidine
- •Amiodarone
- •Arsenic trioxide
- •Cisapride
- •Calcium channel blockers (e.g., lidoflazine)
- 另有 12 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (enzyme inhibitor therapy)
Patients receive belinostat IV over 30 minutes on days 1-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: belinostat (Drug)
结局指标
主要结局
Dose-limiting Toxicities (DLT) and Maximum Tolerated Dose (MTD) of Belinostat in Patients With Inoperable HCC (Phase I)
时间窗: Course 1
DLT is defined as any grade 4 hematological toxicity and any grade 3 or 4 non hematological toxicity during cycle 1, excluding alopecia. Specifically, grade 3 nausea, vomiting, or diarrhea that does not respond to therapy is considered dose-limiting. Also, delays in treatment greater than 2 weeks are also dose-limiting. MTD is defined as the dose below which \>= 2 of 3 or \>= 2 of 6 patients experience DLT. Graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Tumor Response in Patients With Inoperable HCC Using Belinostat (Phase II)
时间窗: Every 2 courses (approximately 6 weeks)
Evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. The 95% confidence intervals should be provided.
次要结局
未报告次要终点