Phase I Trial Of Benzoylphenylurea (NSC#639829) In Advanced Malignancy
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Maximum-tolerated dose (MTD) defined as the highest dose level where 0/6 or 1/6 patients experience dose-limiting toxicity (DLT) as assessed by CTCAE version 3.0
研究概览
简要总结
This phase I trial is studying the side effects and best dose of benzoylphenylurea in treating patients with advanced cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die
详细描述
OBJECTIVES:
I. Determine the dose-limiting toxicity and the maximum tolerated dose of benzoylphenylurea in patients with advanced malignancy.
II. Determine the pharmacokinetics of this drug in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive oral benzoylphenylurea weekly for 6 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of benzoylphenylurea until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed malignancy
- •Metastatic or unresectable
- •No standard curative or palliative measures exist or are ineffective
- •Brain metastases allowed provided 1 of the following criteria is met:
- •Lesions were previously treated with surgery, radiotherapy, or chemotherapy AND are currently asymptomatic AND no steroid therapy or antiseizure medication within the past 2 weeks
- •Untreated, asymptomatic metastases AND no requirement for steroid therapy or antiseizure medication
- •Performance status - ECOG 0-2
- •More than 12 weeks
- •WBC at least 3,000/mm^3
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Bilirubin normal
- •SGOT/SGPT no greater than 2.5 times upper limit of normal
- •Albumin at least 3.0 mg/dL
- •Creatinine normal
- •Creatinine clearance at least 60 mL/min
- •No symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
- •No prior allergic reactions to compounds of similar chemical or biologic composition to benzoylphenylurea
- •No neuropathy greater than grade 1
- •No other uncontrolled medical or psychiatric illness that would preclude study compliance
- •No ongoing or active infection
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Prior immunotherapy allowed
- •No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)
- •At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and recovered
- •At least 2 weeks since steroids for CNS disease
- •At least 4 weeks since prior radiotherapy and recovered
- •Prior surgery allowed
- •At least 2 weeks since antiseizure medications for CNS disease
- •More than 7 days since prior CYP3A4 or CYP2D6 inhibitors
- •More than 7 days since prior CYP3A4 inducers
- •No concurrent CYP3A4 or CYP2D6 inhibitors
- •No concurrent CYP3A4 inducers
- •No other concurrent investigational agents
- •No concurrent combination anti-retroviral therapy for HIV
排除标准
- 未提供
研究组 & 干预措施
Treatment (benzoylphenylurea)
Patients receive oral benzoylphenylurea weekly for 6 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of benzoylphenylurea until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 6 patients experience dose-limiting toxicity.
干预措施: benzoylphenylurea (Drug)
Treatment (benzoylphenylurea)
Patients receive oral benzoylphenylurea weekly for 6 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of benzoylphenylurea until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 6 patients experience dose-limiting toxicity.
干预措施: pharmacological study (Other)
结局指标
主要结局
Maximum-tolerated dose (MTD) defined as the highest dose level where 0/6 or 1/6 patients experience dose-limiting toxicity (DLT) as assessed by CTCAE version 3.0
时间窗: 8 weeks
DLT defined as grade 3 or worse non-hematologic and sustained (> 5 days) grade 3 hematologic toxicity or grade 4 hematologic toxicity of any duration, and the moderate toxicity is grade 2 toxicity as assessed by CTCAE version 3.0
时间窗: 8 weeks
Pharmacokinetics of benzoylphenylurea
时间窗: At baseline, at 0.5, 1.0, 1.5, 2, 4, 6, 8, 24, 48, 72, and 96 hours (weeks 1 and 6)
Relationships between drug exposure and toxicity, efficacy, and biological endpoints will be explored using univariate and multivariate analysis techniques.
次要结局
- Response (complete and partial response) rate(Up to 7 years)
- Survival(From the date of first treatment until death or last follow-up, assessed up to 7 years)