NCT00388089已完成1 期
Phase I Study of Weekly Bortezomib (VELCADE, PS-341) and Weekly Topotecan (HYCAMTIN) in Solid Tumor Patients With an Emphasis on Small Cell Lung Cancer (SCLC)
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Safety
研究概览
简要总结
RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with topotecan may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib and topotecan in treating patients with advanced solid tumors.
详细描述
OBJECTIVES:
Primary
- Evaluate the safety and feasibility of bortezomib and topotecan hydrochloride in patients with advanced solid tumors.
Secondary
- Determine the maximum tolerated dose (MTD) of bortezomib and topotecan hydrochloride in these patients.
- Determine, preliminarily, the efficacy of this regimen in these patients.
- Perform laboratory correlative studies on tumor tissue and blood samples from these patients to investigate potential predictors of response.
- Obtain fresh tumor tissue for correlative studies from a subset of patients with small cell lung cancer treated at the MTD.
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
- •DISEASE CHARACTERISTICS:
- •Histologically or cytologically confirmed advanced solid tumor, meeting 1 of the following criteria:
- •Disease progressed after ≥ 1 prior standard therapy regimen
- •Treatment-naive with no standard therapy of curative intent available
- •Not a candidate for standard therapy due to poor performance status
- •Patients with small cell lung cancer are enrolled after the maximum tolerated dose has been determined
- •Must have tumor accessible for biopsy
- •Measurable disease by RECIST criteria or evaluable disease (e.g., pleural effusion, ascites, or bone metastasis)
- •Disease in previously irradiated sites is considered measurable provided there is clear disease progression after radiotherapy
- •Asymptomatic brain metastasis treated by prior surgical resection or radiotherapy allowed if both of the following criteria are met:
- •Neurologically stable
- •Off steroids and anticonvulsants for ≥ 4 weeks
- •PATIENT CHARACTERISTICS:
- •Karnofsky performance status 60-100%
- •Life expectancy ≥ 3 months
- •Absolute neutrophil count ≥ 1,500/mm³
- •Platelet count ≥ 100,000/mm³
- •Creatinine clearance ≥ 40 mL/min
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •AST and ALT ≤ 3.0 times ULN
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No preexisting neuropathy ≥ grade 2 within the past 14 days
- •No hypersensitivity to bortezomib, boron, or mannitol
- •No myocardial infarction within the past 6 months
- •No New York Heart Association class III or IV heart failure
- •No uncontrolled angina, severe uncontrolled ventricular arrhythmias, or ECG evidence of acute ischemia or active conduction system abnormalities
- •PRIOR CONCURRENT THERAPY:
- •See Disease Characteristics
- •Any number of prior chemotherapy regimens allowed
- •At least 4 weeks since prior chemotherapy and recovered
- •At least 2 weeks since prior radiotherapy and recovered
- •No prior topotecan hydrochloride or bevacizumab
- •At least 14 days since prior investigational drugs
- •No concurrent anticonvulsants metabolized by the cytochrome P450 pathway
排除标准
- 未提供
结局指标
主要结局
Safety
时间窗: Monitored on an ongoing basis during the study
If cumulative toxicities are seen in subsequent treatment cycles, a decision regarding modification or discontinuation of the study drug and/or patient enrollment will be made by the sponsor in conjunction with the investigator.
次要结局
- Toxicity(On Day 8 and at beginning of subsequent cycles)
- Response rate(At baseline and every 2 courses during treatment)
- Best response(From start of treatment until disease progression/recurrence)
- Survival(From registration to time of death due to any cause)
- Progression-free survival(From registration to the first observation of disease progression or death due to any cause)
- Topoisomerase levels as assessed by western blot and tumor tissue biopsy(From pre-treatment to post-treatment)
- NF-kB and BCL-2 family activity as assessed by immunohistochemistry(From pre-treatment to post-treatment)
- Loss of p27 as assessed by immunohistochemistry(From pre-treatment to post-treatment)
- Hypoxia-induced plasma proteins as measured by enzyme-linked immunosorbent assay (ELISA)(From pre-treatment to post-treatment)
- Shed tumor DNA in plasma(From pre-treatment to post-treatment)
- Biological activity of bortezomib as measured by flow cytometry(From pre-treatment to post-treatment)
研究者
研究点 (1)
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