Phase I Study Of R(+)XK469 In Patients With Advanced Neuroblastoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 85
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose of XK469 in pediatric patients with advanced neuroblastoma
研究概览
简要总结
This phase I trial is studying the side effects and best dose of R(+)XK469 in treating patients with advanced neuroblastoma. Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die.
详细描述
OBJECTIVES:
I. Determine the maximum tolerated dose, recommended phase II dose, and dose-limiting toxicity of R(+)XK469 in two different dosing schedules in patients with advanced neuroblastoma.
II. Determine the safety of this drug in these patients. III. Determine the tolerance to this drug in these patients. IV. Determine the pharmacokinetics and pharmacodynamics of this drug and its metabolites in these patients.
V. Determine, preliminarily, any antineoplastic activity of this drug in these patients.
OUTLINE: This is a dose-escalation study.
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
- 5 Years 至 20 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed high-risk neuroblastoma that has relapsed or is refractory to standard therapy
- •No active brain metastases
- •Previously treated brain metastases allowed if there is no requirement for corticosteroids or anticonvulsants
- •Performance status - Karnofsky performance status 70-100% or Lansky score ≥ 70 for your pediatric patients
- •More than 3 months
- •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 (unless due to documented Gilbert's syndrome)
- •Creatinine less than 1.5 times upper limit of normal
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No other concurrent uncontrolled illness that would preclude study participation
- •No ongoing or active infection
- •No psychiatric illness or social situation that would preclude study participation
- •No prior allergic reaction to compounds of similar chemical or biological composition to study drug (e.g., flurbiprofen or ibuprofen)
- •No HIV-positive patients
- •No concurrent biologic agents
- •At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
- •No other concurrent chemotherapy
- •See Disease Characteristics
- •At least 4 weeks since prior radiotherapy
- •No concurrent palliative radiotherapy
- •See Disease Characteristics
- •Recovered from all prior therapy
- •No other concurrent investigational agents
- •No concurrent commercial agents or therapies directed at malignancy
- •No concurrent combination anti-retroviral therapy for HIV-positive patients
排除标准
- 未提供
研究组 & 干预措施
Treatment (chemotherapy)
SCHEDULE A: Patients receive R(+)XK469 IV over 30 minutes on days 1, 3, and 5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of R(+)XK469 until the recommended phase II dose or MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued and treated at the recommended phase II dose (for a maximum of 20 patients treated at that dose).
SCHEDULE B: Once the recommended phase II dose is determined on schedule A, additional patients are accrued and receive escalating doses of R(+)XK469 IV over 30-60 minutes on day 1, beginning at a reduced dose. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Dose escalation continues as in Schedule A.
干预措施: R(+)XK469 (Drug)
结局指标
主要结局
Maximum tolerated dose of XK469 in pediatric patients with advanced neuroblastoma
时间窗: Day 29 of course 1
Defined as the highest dose studied for which the incidence of dose-limiting toxicity (DLT) was less than 33%.
DLT
时间窗: Day 29 of course 1
Defined as the occurrence of any of the following: 1) grade 3 or higher nonhematologic toxicity except fatigue, alopecia, nausea, vomiting, 2) grade 4 thrombocytopenia or anemia, 3) any fever accompanied by granulocyte count \< 1000/mm\^3 (grade 3 or 4 neutropenia), 4) failure to recover absolute neutrophil count 1500/μL
Recommended phase II dose
时间窗: Day 29 of course 1
Generally defined as the MTD. For both schedules A and B and the pediatric dosing schedule, once the recommended phase II dose has been tentatively defined, a total of 12 evaluable patients will be studied to ensure the feasibility of this dose for phase II trials. If interindividual pharmacokinetic variability is high, additional patients will be enrolled (maximum of 20 at the phase II dose) to permit adequate pharmacological characterization of XK469 and the relationship of interindividual pharmacokinetic variability to toxicity.
次要结局
- Pharmacodynamics of XK469 in pediatric patients(Continuously over the course of study treatment)
- Metabolism of XK469 in pediatric patients(Days 1-3 of course 1)
- Antineoplastic activity of XK469 for neuroblastoma(Every 2 courses)
- Pharmacokinetics of XK469 in pediatric patients(Days 1-3 of course 1)