A Phase I Study Of PS-341 In Pediatric Patients With Refractory Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Progression free survival
研究概览
简要总结
Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Phase I trial to study the effectiveness of bortezomib in treating children who have advanced solid tumors that have not responded to previous treatment.
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of bortezomib in pediatric patients with refractory solid tumors.
II. Determine the dose-limiting toxicity and other toxic effects of this regimen in these patients.
III. Preliminarily determine the antitumor activity of this regimen in these patients.
OUTLINE: This is a dose-escalation study.
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
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed solid tumor that is refractory to standard therapy or for which no standard therapy exists
- •Histologic confirmation not required for brainstem glioma or optic pathway tumor
- •Ineligible for therapies of higher priority
- •Stratum II only:
- •No bone marrow involvement
- •Performance status - Karnofsky 50-100% (over 10 years of age)
- •Performance status - Lansky 50-100% (10 years of age and under)
- •At least 8 weeks
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 75,000/mm^3 (transfusion independent)
- •Hemoglobin at least 8 g/dL (RBC transfusions allowed)
- •Bilirubin less than 1.5 mg/dL
- •ALT less than 5 times normal for age
- •Albumin at least 2 g/dL
- •Creatinine no greater than upper limit of normal for age
- •Creatinine clearance or radioisotope glomerular filtration rate greater than 70 mL/min
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Neurologic deficits related to CNS tumors allowed if relatively stable for at least 2 weeks
- •No uncontrolled infection
- •At least 7 days since prior biologic therapy and recovered
- •At least 3 months since prior allogeneic stem cell transplantation
- •At least 1 week since prior growth factors
- •Stratum II only:
- •No prior stem cell transplantation with or without total body irradiation
- •At least 2 weeks since prior chemotherapy (4 weeks for nitrosoureas) and recovered
- •Stratum II only:
- •No more than 2 prior multi-agent chemotherapy regimens
- •More than 2 single-agent regimens allowed
- •Concurrent dexamethasone allowed for CNS tumors if stable dose for at least 2 weeks
- •See Biologic therapy
- •At least 2 weeks since prior palliative local radiotherapy
- •At least 6 months since prior craniospinal radiotherapy or radiotherapy to at least 50% of pelvis
- •At least 6 weeks since prior substantial bone marrow radiotherapy
- •Recovered from prior radiotherapy
- •Stratum II only:
- •No prior radiotherapy to more than 20% of bone marrow
- •No prior bortezomib
- •No concurrent anticonvulsants
- •No other concurrent investigational agents
排除标准
- 未提供
研究组 & 干预措施
Treatment (bortezomib)
Patients receive bortezomib IV on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: bortezomib (Drug)
Treatment (bortezomib)
Patients receive bortezomib IV on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Treatment (bortezomib)
Patients receive bortezomib IV on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
结局指标
主要结局
Progression free survival
时间窗: Up to 24 months
MTD defined as the dose at which fewer than 20% of patients experience DLT assessed using CTC version 2.0
时间窗: 3 weeks
20S proteasome inhibition
时间窗: Up to 2 weeks
The 95% confidence interval for the percent of patients who exhibit inhibition at a recommended dose level determined according to the table above is 61%-100%, if six patients are evaluated or 55%-100% if five patients are evaluated.
次要结局
未报告次要终点