A Dose-Finding, Safety, And Pharmacokinetic Study Of The Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor OSI-774 (NSC 718781) In Patients With Unresectable Hepatocellular Carcinoma And Moderate Hepatic Dysfunction
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Dose-limiting toxicity and maximum tolerated dose as measured by NCI CTCAE v3.0 continuously
研究概览
简要总结
Phase I trial to study the effectiveness of erlotinib in treating patients who have unresectable liver cancer and liver dysfunction. Biological therapies such as erlotinib may interfere with the growth of tumor cells and slow the growth of the tumor
详细描述
PRIMARY OBJECTIVES:
I. Establish the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of OSI-774 in patients with unresectable hepatocellular carcinoma (HCC) with moderate liver dysfunction.
II. Establish the pharmacokinetic and pharmacodynamic profile of OSI-774 in HCC patients with moderate liver dysfunction.
SECONDARY OBJECTIVES:
I. Assess possible anti-tumor effects of OSI-774 in patients with advanced hepatocellular carcinoma in terms of partial response (PR) and complete response (CR) as assessed by tumor shrinkage by RECIST criteria.
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 unresectable hepatocellular carcinoma (HCC) with or without extrahepatic metastasis
- •No fibrolamellar HCC
- •No more than 2 prior therapies for HCC, including systemic chemotherapy, chemoembolization, hepatic arterial infusion of chemotherapeutic agents, and other novel agents
- •Measurable disease
- •At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
- •Moderate hepatic dysfunction with any of the following:
- •Bilirubin 2-4 g/dL
- •Albumin < 2.5 g/dL
- •PT 2-4 seconds > upper limit of normal (ULN)
- •AST/ALT 2.6-10 times > ULN
- •No known brain metastases
- •No ascites that are refractory to conservative management (e.g., sodium restriction to 50 mEq/day dietary sodium and fluid restrictions and/or diuretics)
- •Performance status - ECOG 0-2
- •At least 16 weeks
- •Granulocyte count ≥ 1,500/mm^3
- •Platelet count ≥ 60,000/mm^3
- •Hemoglobin ≥ 10 g/dL
- •No decompensated liver disease
- •No jaundice
- •No portosystemic encephalopathy (evidenced by confusion, asterixis, significant sleep disturbance, or hypothermia less than 36º Celsius)
- •No hyponatremia < 130 mEq/L
- •No portal hypertension with bleeding esophageal or gastric varices within the past 3 months
- •Creatinine ≤ 2 mg/dL
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •No gastrointestinal tract disease resulting in an inability to take oral medication or requirement for IV alimentation
- •No active peptic ulcer disease
- •No abnormalities of the cornea (e.g., dry eye syndrome or Sjögren's syndrome)
- •No congenital abnormality (e.g., Fuch's dystrophy)
- •No significant traumatic injury within the past 21 days
- •No other uncontrolled concurrent illness that would preclude study participation
- •No ongoing or active infection
- •No psychiatric illness or social situation that would preclude study compliance
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- •At least 4 weeks since prior radiotherapy and recovered
- •No prior surgical therapy affecting absorption
- •At least 21 days since prior major surgery
- •At least 4 weeks since any other prior agents and recovered
- •No prior epidermal growth factor-receptor targeting therapies
- •No other concurrent investigational agents
- •No concurrent combination antiretroviral therapy for HIV-positive patients
排除标准
- 未提供
研究组 & 干预措施
Treatment (erlotinib hydrochloride)
Patients receive oral erlotinib once daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
干预措施: erlotinib hydrochloride (Drug)
Treatment (erlotinib hydrochloride)
Patients receive oral erlotinib once daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
干预措施: pharmacological study (Other)
Treatment (erlotinib hydrochloride)
Patients receive oral erlotinib once daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Dose-limiting toxicity and maximum tolerated dose as measured by NCI CTCAE v3.0 continuously
时间窗: 28 days
Pharmacokinetic (PK) and pharmacodynamic profile, as measured by Cmax, Tmax, AUC0-24, AUC0-infinity, Cl/F, T1/2, accumulation ratio, and Cssmin
时间窗: Days 8-28
PK parameters characterized by use of descriptive statistics. Nonparametric statistical test for several unrelated (Kruskal-Wallis ANOVA) or related (Wilcoxon matched-pairs signed-rank test) parameters used. Relationships between drug dose and indices that reflect drug exposure (Cmax, AUC, Cssmin) evaluated with Kruskal-Wallis one-way ANOVA test. Extent of drug exposure (Cmax, AUC, Cssmin) compared among patients with various grades of toxicity using nonparametric statistical tests for two (Mann-Whitney U test) or several (Kruskal-Wallis one-way ANOVA) independent samples.
次要结局
- Objective response rates (partial, complete, stable disease), as measured by CT scans using RECIST criteria(Up to 3 years)