NCT02150733已完成1 期
A Phase 1, Open-Label Study Assessing the Impact of Hepatic Impairment on the Pharmacokinetics of Tivantinib in Subjects With Advanced Solid Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Composite of plasma pharmacokinetic parameters of Tivantinib
研究概览
简要总结
This is a multi-center, open-label, Phase 1 study to evaluate the impact of hepatic impairment on the pharmacokinetics of Tivantinib in cancer subjects with varying degrees of hepatic function, from normal to severely impaired.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Subjects must have histologically or cytologically confirmed advanced solid tumor. However, Hepatocellular Carcinoma (HCC) subjects are allowed without histological confirmation as long as there is radiological diagnosis as per standard criteria
- •Male or female ≥18 years of age
- •Life expectancy of >12 weeks
- •Women of childbearing potential (WOCBP) must have a negative pregnancy test performed prior to the start of study drug
- •Male subjects and WOCBP must agree to use double barrier contraceptive measures or avoid intercourse during the study and for 90 days after the last dose of study drug
- •Subjects with impaired hepatic function will be grouped according to Child-Pugh classification score
- •Subjects with biliary obstruction for whom a biliary drain or stent has been placed are eligible, provided that the drain or stent has been in place for at least 10 days prior to the first dose of Tivantinib, and the subject's liver function has stabilized as defined by 2 measurements at least 5 days apart that put the subject in the same hepatic impairment group
- •Eastern Cooperative Oncology Group (ECOG) performance status ≥2
- •Adequate bone marrow and renal function
- •Ability to provide written informed consent, comply with protocol visits and procedures, take oral medication, and not have any active infection or chronic comorbidity that would interfere with therapy
- •Fully informed about their illness and the investigational nature of the study protocol and must sign and date an Institutional Review Board-approved Informed Consent Form
排除标准
- •History of liver transplant
- •Any major surgical procedure within 3 weeks prior to the first dose of study drug;
- •Active, clinically serious infections defined as ≥Grade 2 according to NCI Common Toxicity Criteria for Adverse Effects (CTCAE), version 4.0
- •Known metastatic brain or meningeal tumors, unless the subject is >3 months from definitive therapy and clinically stable (supportive therapy with steroids or anticonvulsant medications is allowed) with respect to the tumor at the time of the first dose of study drug
- •History of cardiac disease
- •Active coronary artery disease, defined as myocardial infarction, unstable angina, coronary bypass graft, or stenting within 6 months prior to study entry
- •Evidence of uncontrolled bradycardia or other cardiac arrhythmia defined as ≥Grade 2 according to NCI CTCAE, version 4.0, or uncontrolled hypertension
- •Any condition that is unstable or that could jeopardize the safety of the subject and the subject's protocol compliance, including known infection with human immunodeficiency virus
- •Significant gastrointestinal disorders, in the opinion of the Investigator
- •Pregnant or breastfeeding
- •Received Tivantinib as prior therapy
- •Received anti-cancer therapy, including antibody, retinoid, or hormonal treatment (except megestrol acetate as supportive care), and radiation, within 3 weeks before dosing. Prior and concurrent use of hormone replacement therapy, the use of gonadotropin-releasing hormone modulators for prostate cancer, and the use of somatostatin and analogs for neuroendocrine tumors are permitted
- •Any other investigational drug/medical device within 3 weeks prior to the first dose
- •Substance abuse or medical, psychological, or social conditions that, in the opinion of the Investigator, may interfere with the subject's participation in the clinical study or evaluation of the clinical study results
- •Subjects receiving Coumadin anticoagulants
- •Inability to swallow oral medications
- •Administration or possibility of initiating or continuing any treatment with any known Cytochrome P450 3A4 (CYP3A4) and CYP2C19 enzyme and P-glycoprotein altering drugs (inducer or inhibitor) or non drug agents within 14 days prior to dosing and during the primary objective phase
研究组 & 干预措施
Group 1 - Normal hepatic function
Experimental
Subjects with normal hepatic function
干预措施: Tivantinib (Drug)
Group 2 - Mild hepatic impairment
Experimental
Subjects with mild hepatic impairment by Child-Pugh classification scores
干预措施: Tivantinib (Drug)
Group 3 - Moderate hepatic impairment
Experimental
Subjects with moderate hepatic impairment by Child-Pugh classification scores
干预措施: Tivantinib (Drug)
Group 4 - Severe hepatic impairment
Experimental
Subjects with severe hepatic impairment by Child-Pugh classification scores
干预措施: Tivantinib (Drug)
结局指标
主要结局
Composite of plasma pharmacokinetic parameters of Tivantinib
时间窗: 0 (predose), 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours after a single dose and 0 (predose), 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours after Cycle 1 Day 11 dose
The following pharmacokinetic parameters will be determined: population estimates of apparent total clearance (CL/F), apparent volume of distribution (V/F), area under the concentration-time curve during the dosing interval (AUCtau), and maximum concentration (Cmax) during the dosing interval.
次要结局
- Composite of plasma pharmacokinetic parameters of Tivantinib(0 (predose), 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours after a single dose and 0 (predose), 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours after Cycle 1 Day 11 dose)
- Composite of plasma pharmacokinetic parameters of Tivantinib metabolites(0 (predose), 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours after a single dose and 0 (predose), 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours after Cycle 1 Day 11 dose])
研究者
研究点 (1)
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