PHASE I, PHARMACOKINETIC, PHARMACODYNAMIC TRIAL OF PTK787 AND PACLITAXEL IN C

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这将是一项单中心I期研究，将进入符合纳入标准的患者，并且没有下列排除标准。我们计划研究PTK787联合紫杉醇治疗晚期实体肿瘤患者。这项研究的主要目标如下：“评估增加剂量的紫杉醇与PTK787联合使用的安全性和耐受性。“评价PTK787和紫杉醇单独及联合用药的药代动力学”评价PTK787和紫杉醇的药效学活性。通过放射学方法评价PTK787和紫杉醇的药效学作用。利用C11一氧化碳正电子发射计算机断层扫描评价肿瘤血流的变化。患者将按顺序进入6个队列中的1个队列，每个队列由3~6名患者组成。将评估六个剂量水平。从D-11开始，PTK787的剂量水平将分别为250、500、750、1000和1250毫克。紫杉醇的剂量水平分别为75、85、100 mg/m2，静脉滴注，第1、8、15天，每28天一次。在纳入下一个队列之前，将在28天的治疗周期中对队列中的所有患者进行安全性评估。这项研究将包括筛查和基准期、磨合期和治疗期，其中包括28天的研究用药。PTK787将一直持续到出现与治疗相关的重大毒性或疾病进展。紫杉醇将在毒性允许的情况下继续使用，直到进展，最多6个周期。这项研究的评估如下：“治疗突发不良事件，包括实验室评估和直接神经”检查“肿瘤测量和肿瘤标记物测量(如果适用)”全血样本的药代动力学评估

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. " This will be a single center Phase I study which will enter patients who meet the inclusion criteria and exhibit none of the exclusion criteria listed below. We plan on studying PTK787 plus paclitaxel in patients with advanced solid tumors. The primary objectives of this study are as follows: " To evaluate the safety and tolerability of escalating doses of paclitaxel in combination with PTK787. " To evaluate the pharmacokinetics of PTK787 and paclitaxel alone and in combination from patients with cancer accrued to this study " To evaluate the pharmacodynamic activity of PTK787 and paclitaxel via radiographic changes caused by the combination utilizing C11 Carbon Monoxide PET scanning to evaluate tumor blood flow changes with therapy Patients will be enrolled sequentially into 1 of 6 cohorts and each cohort will consist of 3 to 6 patients. Six dose levels will be assessed. The dose levels of PTK787 will be 250, 500, 750, 1000, and 1250 mg administered orally every day starting on D-11. The dose levels of Paclitaxel will be 75, 85,100mg/m2 IV given on days 1, 8, and 15 every 28 days. All patients in a cohort will be evaluated for safety throughout the 28-day treatment cycle prior to enrollment of the next cohort. The study will consist of a Screening and Baseline Period, Run-in Period, Treatment Period consisting of 28 days of study drug administration. PTK787 will continue until the appearance of significant treatment-related toxicities or disease progression. Paclitaxel will be continued until progression as toxicity permits with a maximum of 6 cycles. The assessments for this study are as follows: " Treatment emergent adverse events including laboratory assessments and directed neurological " Examinations " Tumor measurements and measurements of tumor markers (if appropriate) " Pharmacokinetic assessments from whole blood sample