A Phase I and Pharmacologic Study of the Proteasome Inhibitor PS-341 in Combination With Paclitaxel and Carboplatin in Patients With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 96
- 试验地点
- 1
- 主要终点
- MTD of paclitaxel, bortezomib, and carboplatin defined as the highest safely-tolerated dose where =< 1 patient experience dose-limiting toxicity (DLT) with the next higher dose having at least 2 patients who experience DLT as assessed by CTC version 2.0
研究概览
简要总结
Phase I trial to study the effectiveness of combining PS-341 and combination chemotherapy in treating patients who have advanced solid tumors. PS-341 may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining PS-341 and chemotherapy may kill more tumor cells
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of bortezomib and paclitaxel administered in combination with carboplatin in patients with advanced solid tumors.
II. Compare the tolerability and efficacy of the different sequences of this regimen in these patients.
III. Determine the clinical toxic effects and pharmacokinetics of this regimen in these patients.
IV. Determine, preliminarily, the therapeutic activity of this regimen in these patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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 confirmed malignancy for which no known standard therapy that is potentially curative or definitely capable of extending life expectancy exists
- •No hematologic malignancies
- •No symptomatic CNS metastases
- •Brain metastases allowed if previously treated (radiotherapy and/or surgery)and patient is stable for at least 8 weeks
- •Performance status - ECOG 0-2
- •At least 12 weeks
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- •AST no greater than 2.5 times ULN
- •Creatinine no greater than 1.5 times ULN
- •No New York Heart Association class III or IV heart disease
- •HIV negative
- •No peripheral neuropathy grade 2 or greater
- •No uncontrolled infection
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •More than 4 weeks since prior biologic therapy
- •More than 4 weeks since prior immunotherapy
- •No prior bone marrow transplantation
- •No concurrent immunotherapy
- •More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- •No other concurrent chemotherapy
- •More than 4 weeks since prior radiotherapy
- •No prior radiotherapy to more than 30% of bone marrow
- •No concurrent radiotherapy
- •No concurrent investigational ancillary therapy
- •No concurrent enrollment in another study involving a pharmacologic agent (e.g., drugs, biologics, immunotherapy, or gene therapy) for symptom control or therapeutic intents
排除标准
- 未提供
研究组 & 干预措施
Group I (paclitaxel, carboplatin, bortezomib)
Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and bortezomib IV over 3-5 seconds on days 2, 5, and 8.
干预措施: bortezomib (Drug)
Group I (paclitaxel, carboplatin, bortezomib)
Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and bortezomib IV over 3-5 seconds on days 2, 5, and 8.
干预措施: paclitaxel (Drug)
Group I (paclitaxel, carboplatin, bortezomib)
Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and bortezomib IV over 3-5 seconds on days 2, 5, and 8.
干预措施: carboplatin (Drug)
Group I (paclitaxel, carboplatin, bortezomib)
Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and bortezomib IV over 3-5 seconds on days 2, 5, and 8.
干预措施: laboratory biomarker analysis (Other)
Group II (bortezomib, paclitaxel, carboplatin)
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, and 8 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 2
干预措施: bortezomib (Drug)
Group II (bortezomib, paclitaxel, carboplatin)
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, and 8 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 2
干预措施: paclitaxel (Drug)
Group II (bortezomib, paclitaxel, carboplatin)
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, and 8 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 2
干预措施: carboplatin (Drug)
Group II (bortezomib, paclitaxel, carboplatin)
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, and 8 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 2
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
MTD of paclitaxel, bortezomib, and carboplatin defined as the highest safely-tolerated dose where =< 1 patient experience dose-limiting toxicity (DLT) with the next higher dose having at least 2 patients who experience DLT as assessed by CTC version 2.0
时间窗: 21 days
Number of toxicity incidents as assessed by CTC Version 2.0
时间窗: 21 days
Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.
次要结局
- Number of responses(Up to 3 months)
- Change in p53 accumulation(From baseline to up to 3 months)
- Change in other proteasome levels(From baseline to up to 3 months)