A Phase I Study of Epothilone B Analog BMS 247550 in Combination With Carboplatin in Recurrent and/or Refractory Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- MTD of ixabepilone defined as the first dosage tier below the MAD in which =< 1/6 patients experiences a DLT
研究概览
简要总结
This phase I trial is studying the side effects and best dose of BMS-247550 when given together with carboplatin in treating patients with recurrent or refractory solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells
详细描述
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.
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 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)
排除标准
- 未提供
研究组 & 干预措施
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
干预措施: ixabepilone (Drug)
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
干预措施: carboplatin (Drug)
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
干预措施: laboratory biomarker analysis (Other)
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
干预措施: pharmacological study (Other)
结局指标
主要结局
MTD of ixabepilone defined as the first dosage tier below the MAD in which =< 1/6 patients experiences a DLT
时间窗: 28 days
次要结局
- Pharmacokinetics of ixabepilone and carboplatin(Week 1)