Bortezomib and Docetaxel in Treating Patients With Advanced Solid Tumors
A Phase 1 Study of PS-341 in Combination With Docetaxel in Patients With Advanced Solid Tumors
研究概览
详细说明
OBJECTIVES:
I. Determine the maximum tolerated dose of bortezomib and docetaxel in patients with advanced solid tumors.
II. Determine the toxicity and tolerability of this regimen in these patients. III. Determine the biologic correlates of proteasome inhibition of bortezomib and determine the effects of this inhibition on the pharmacokinetics of docetaxel in these patients.
IV. Determine the antitumor efficacy of this regimen in these patients.
OUTLINE: This is a dose-escalation study.
For course 1, patients receive docetaxel IV over 1 hour on days 1 and 8 and bortezomib IV over 3-5 seconds on days 9 and 12. Patients then receive 1 week of rest. For course 2 and all subsequent courses, patients receive docetaxel on days 1 and 8 and bortezomib on days 2, 5, 9, and 12. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 2-6 patients receive escalating doses of bortezomib and docetaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6 patients experiences dose-limiting toxicity.
PROJECTED ACCRUAL: A minimum of 24 patients will be accrued for this study.
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
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Maryland
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Baltimore、Maryland、美国、21287-8936
- Johns Hopkins University
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
Histologically confirmed solid tumor for which standard curative or palliative measures do not exist or are no longer effective
- Metastatic or unresectable disease
- No known brain metastases
- Performance status - ECOG 0-2
- Performance status - Karnofsky 50-100%
- 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
- Hemoglobin at least 8 g/dL
- Bilirubin normal
- AST and ALT no greater than 1.5 times upper limit of normal (ULN) and alkaline phosphatase no greater than 2.5 times ULN
- Alkaline phosphatase no greater than 5 times ULN (unless bone-derived) and AST and ALT less than 1.5 times ULN
- Creatinine normal
- Creatinine clearance at least 60 mL/min
- 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 during and for 3 months after study
- No prior allergic reactions attributed to taxanes (e.g., docetaxel or paclitaxel) or compounds of similar chemical or biological composition
- No prior allergic reactions to compounds similar to bortezomib or other study agents
- No known hypersensitivity to corticosteroids
- No predicted intolerance to regular, repeated administration of corticosteroids (e.g., poorly controlled diabetes or significant osteoporosis/osteopenia)
- No ongoing or active infection
- No other uncontrolled concurrent illness that would preclude study participation
- No psychiatric illness or social situation that would preclude study participation
- No peripheral neuropathy grade 2 or greater
At least 4 weeks since prior chemotherapy (6 weeks for carmustine, nitrosoureas, or mitomycin) and recovered
- No more than 3 courses of mitomycin
Prior taxanes allowed
- At least 6 months since prior docetaxel administered on a weekly schedule
- At least 4 weeks since prior radiotherapy and recovered
- No other concurrent investigational agents
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent anticancer agents or therapies (commercial or investigational)
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：Treatment (docetaxel, bevacizumab)
For course 1, patients receive docetaxel IV over 1 hour on days 1 and 8 and bortezomib IV over 3-5 seconds on days 9 and 12. Patients then receive 1 week of rest.
For course 2 and all subsequent courses, patients receive docetaxel on days 1 and 8 and bortezomib on days 2, 5, 9, and 12. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 2-6 patients receive escalating doses of bortezomib and docetaxel until the maximum tolerated dose (MTD) is determined.
The MTD is defined as the dose at which no more than 1 of 6 patients experiences dose-limiting toxicity.
|
相关研究
鉴于IV
其他名称：
相关研究
其他名称：
鉴于IV
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
大体时间 |
|---|---|
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Maximum-tolerated dose (MTD) based on the incidence of dose-limiting toxicity (DLT) as assessed by the NCI Common Toxicity Criteria (CTC) version 2.0
大体时间：21 days
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21 days
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Toxicity and tolerability as assessed by NCI CTC version 2.0
大体时间：Up to 30 days after completion of study treatment
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Up to 30 days after completion of study treatment
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次要结果测量
结果测量 |
大体时间 |
|---|---|
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Pharmacokinetics of docetaxel
大体时间：At baseline, at 30 and 60 during infusion, at 10 min, 30 min, 1, 3, 7.5, 24, and 48 hours, and at 8 days after completion of docetaxel infusion
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At baseline, at 30 and 60 during infusion, at 10 min, 30 min, 1, 3, 7.5, 24, and 48 hours, and at 8 days after completion of docetaxel infusion
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Response rate
大体时间：Up to 30 days after completion of study treatment
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Up to 30 days after completion of study treatment
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20S proteasome activity
大体时间：At 1 hour after first PS-341 infusion (week 2, day 2), and at 24 and 48 hours
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At 1 hour after first PS-341 infusion (week 2, day 2), and at 24 and 48 hours
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合作者和调查者
调查人员
- 首席研究员：Deborah Armstrong、Johns Hopkins University
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
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