A Phase I Study of PS-341 (NSC 681239), Carboplatin, and Etoposide in Patients With Advanced Solid Tumors Refractory to Standard Therapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- MTD defined as the dose level below the dose level that results in DLT in >= 2 of 6 new patients assessed using NCI CTC version 2.0
研究概览
简要总结
Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. 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 combining bortezomib with carboplatin and etoposide in treating patients who have advanced solid tumors that have not responded to previous treatment
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose (MTD) of bortezomib, carboplatin, and etoposide in patients with advanced solid tumors refractory to standard therapy.
II. Evaluate biologic effects of bortezomib on relevant targets in the tumor tissues of patients treated with this regimen.
OUTLINE: This is a dose-escalation study of bortezomib, etoposide, and carboplatin.
Patients receive bortezomib IV on days 1 and 8, carboplatin IV over 30 minutes on day 1, and etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity.
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
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed advanced solid tumor cancer for which no curativetherapy exists
- •Clinically stable CNS disease is allowed provided the following criteria are met:
- •No uncontrolled brain metastases or CNS involvement
- •No active seizures
- •On stable dose of antiseizure or steroid medication for at least 7 days before study enrollment
- •Performance status - ECOG 0-2
- •At least 12 weeks
- •Absolute neutrophil count at least 1,500/mm^3
- •Hemoglobin at least 9 g/dL
- •Platelet count at least 100,000/mm^3
- •Bilirubin no greater than 1.5 mg/dL
- •AST/ALT no greater than 2.5 times upper limit of normal
- •Creatinine no greater than 1.5 mg/dL
- •Creatinine clearance at least 60 mL/min
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No active infection
- •No other serious concurrent systemic disorders (including other malignancy)
- •No prior bone marrow or peripheral blood stem cell transplantation
- •No concurrent immunotherapy
- •See Disease Characteristics
- •At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- •Prior carboplatin and/or etoposide allowed
- •No more than 2 prior courses of mitomycin
- •See Disease Characteristics
- •No concurrent hormonal therapy
- •At least 4 weeks since prior radiotherapy and recovered
- •Palliative radiotherapy involving less than 35% bone marrow reserve allowed if completed at least 2 weeks before study enrollment
- •No prior wide-field radiotherapy to 35% or more of bone marrow
- •No prior pelvic radiotherapy
- •No concurrent radiotherapy
- •At least 28 days since prior investigational agents
- •No other concurrent experimental medications
排除标准
- 未提供
研究组 & 干预措施
Treatment (bortezomib, carboplatin, and etoposide)
Patients receive bortezomib IV on days 1 and 8, carboplatin IV over 30 minutes on day 1, and etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: bortezomib (Drug)
Treatment (bortezomib, carboplatin, and etoposide)
Patients receive bortezomib IV on days 1 and 8, carboplatin IV over 30 minutes on day 1, and etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: carboplatin (Drug)
Treatment (bortezomib, carboplatin, and etoposide)
Patients receive bortezomib IV on days 1 and 8, carboplatin IV over 30 minutes on day 1, and etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: etoposide (Drug)
Treatment (bortezomib, carboplatin, and etoposide)
Patients receive bortezomib IV on days 1 and 8, carboplatin IV over 30 minutes on day 1, and etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Treatment (bortezomib, carboplatin, and etoposide)
Patients receive bortezomib IV on days 1 and 8, carboplatin IV over 30 minutes on day 1, and etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
结局指标
主要结局
MTD defined as the dose level below the dose level that results in DLT in >= 2 of 6 new patients assessed using NCI CTC version 2.0
时间窗: 21 days
Biological data
时间窗: Up to 4 years
The variation of these samples as a function of dose and time will be analyzed to define the mathematical function (e.g. linear, exponential, logistic) that best fits and models the data.
次要结局
未报告次要终点