BMS-247550 Plus Carboplatin in Treating Patients With Recurrent or Refractory Solid Tumors
A Phase I Study of Epothilone B Analog BMS 247550 in Combination With Carboplatin in Recurrent and/or Refractory Solid Tumors
研究概览
详细说明
OBJECTIVES:
I. Determine the maximum tolerated dose of BMS-247550 when given in combination with carboplatin in patients with recurrent or refractory solid tumors.
II. Determine the dose-limiting toxicity and safety of this regimen in these patients.
III. Determine the plasma pharmacokinetics of this regimen in these patients. IV. Determine, preliminarily, any antitumor activity of this regimen in these patients.
V. Correlate the protein expression of survivin with the expression of other apoptotic regulators, the apoptotic index, and response in patients treated with this regimen.
OUTLINE: This is a dose-escalation study of BMS-247550.
Patients receive BMS-247550 IV over 1 hour on days 1, 8, and 15 followed by carboplatin IV over 1 hour on day 1. Treatment repeats every 28 days for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients with a complete response (CR) receive 2 additional courses after achieving CR or up to a total of 6 courses. The first two cohorts of 3-6 patients each receive escalating doses of BMS-247550 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 (DLT).The third and fourth cohorts of 10 patients each receive escalating doses of BMS-247550 until the MTD is determined. The MTD is defined as the dose preceding that at which at least 3 of 10 patients experience DLT. Once the MTD is determined for the third and fourth cohorts, 15 additional patients are treated at the MTD. Patients are followed for 30 days.
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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Florida
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Tampa、Florida、美国、33612
- H. Lee Moffitt Cancer Center and Research Institute
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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 or cytologically confirmed metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective
- Measurable or evaluable disease
Lesion accessible for core or excisional biopsy if being treated at the maximum tolerated dose (MTD)
- No biliary tract dilation if radiologically guided biopsy of the liver is planned
- No requirement for core biopsy of lung lesion that is not pleural based
- No requirement for laparotomy or thoracotomy solely for biopsy
- No medical condition that would preclude biopsy
- No known brain metastases
- Performance status - ECOG 0-2
- Performance status - ECOG 0-1 if being treated at the MTD
- More than 3 months
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- No prior bleeding disorder or unexplained bleeding if being treated at the MTD
- Bilirubin no greater than 1.5 mg/dL
- AST/ALT no greater than 2 times upper limit of normal (ULN) (5 times ULN if liver metastases present)
- PT/PTT normal
- Creatinine no greater than 1.5 times ULN
- 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
- No other concurrent uncontrolled illness that would preclude study participation
- No ongoing or active infection
- No grade 2 or greater neuropathy (sensory or motor)
- No prior severe allergic reaction attributable to compounds containing Cremophor EL or platinum agents
- No psychiatric illness or social situation that would preclude study compliance
- No medical condition that would preclude study if being treated at the MTD
- At least 4 week since prior immunotherapy
- At least 24 hours since prior growth factors
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- No more than 3 prior chemotherapy regimens
- No prior epothilone agents
- At least 1 week since prior hormonal therapy directed at malignancy
- Concurrent hormone replacement therapy allowed
- At least 4 weeks since prior wide-field radiotherapy involving 30% or more of bone marrow
- See Disease Characteristics
- At least 4 weeks since prior investigational agents
- No prior or concurrent St. John's Wort
- No concurrent combination anti-retroviral therapy for HIV-positive patients
- No other concurrent investigational agents
- No concurrent heparin or other anticoagulants if being treated at the MTD
- No concurrent inhibitors of cytochrome P450 3AP (CYP3A4)
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 (ixabepilone, carboplatin)
Patients receive BMS-247550 IV over 1 hour on days 1, 8, and 15 followed by carboplatin IV over 1 hour on day 1.
Treatment repeats every 28 days for at least 2 courses in the absence of disease progression or unacceptable toxicity.
Patients with a CR receive 2 additional courses after achieving CR or up to a total of 6 courses
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相关研究
相关研究
其他名称:
鉴于IV
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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MTD of ixabepilone defined as the first dosage tier below the MAD in which =< 1/6 patients experiences a DLT
大体时间:28 days
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28 days
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次要结果测量
结果测量 |
大体时间 |
|---|---|
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Pharmacokinetics of ixabepilone and carboplatin
大体时间:Week 1
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Week 1
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合作者和调查者
调查人员
- 首席研究员:Daniel Sullivan、H. Lee Moffitt Cancer Center and Research Institute
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
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