CLINICAL TRIAL: PHASE 1 CLINICAL TRIAL OF DAILY ORAL GLEEVE AND ONE HOUR WEEKLY

临床试验：每日口服手套和每周一小时的第一阶段临床试验

• 批准号: 7719032
• 负责人: JOHN L. MARSHALL
• 金额: $ 9.92万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7719032
• 关键词: Anaphase; Angiogenesis Inhibitors; Antineoplastic Agents; Antitumor Response; Biopsy; Cancer Patient; Cell Cycle; Cell Proliferation; Chronic Myeloid Leukemia; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Daily; Dose-Limiting; Drug Kinetics; Funding; Gastrointestinal Stromal Tumors; Gleevec; Grant; Hour; Institution; Maximum Tolerated Dose; Metaphase; Microtubule Stabilization; Microtubules; Mitotic; New Agents; Non-Small-Cell Lung Carcinoma; Oral; Paclitaxel; Pathway interactions; Patients; Phase I Clinical Trials; Platelet-Derived Growth Factor Receptor; Protein Tyrosine Kinase; Refractory; Research; Research Personnel; Resources; Safety; Secondary to; Source; Taxane Compound; Toxic effect; United States National Institutes of Health; chemotherapy; cohort; depolymerization; malignant breast neoplasm; preclinical study; receptor expression; response; taxane; tumor

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. Gleevec has shown activity in chronic myeloid leukemia (CML) and gastrointestinal stromal tumors via potent activity against Bcr-Abl, platelet-derived growth factor receptor, and the C-Kit activated tyrosine kinase pathway. Paclitaxel has broad antitumor activity on microtubules via its action on microtubular assembly and stabilization of the microtubules against depolymerization, thereby inhibiting cellular proliferation by inducing a sustained mitotic block at the metaphase-anaphase portion of the cell cycle. Previous preclinical studies have shown significant synergistic effects when other chemotherapy agents have been combined with Gleevec, however Paclitaxel has not been evaluated in such a comparison. By combining the broad acting agent Paclitaxel with the new agent Gleevec we may observe additive or even synergistic effects without significant increases in toxicities secondary to independent antineoplastic mechanisms SPECIFIC AIMS: Primary Aims: + Determine the dose-limiting toxicity and maximum tolerated dose of Gleevec and Paclitaxel when given in combination to patients with advanced tumors. + Characterize the pharmacokinetics of Gleevec and Paclitaxel when given in combination. Secondary Aims: + Document any objective antitumor response in patients treated with Gleevec and Paclitaxel. + Document the relationship between C-Kit and platelet derived growth factor receptor (PDGF-R) expression on tumor biopsies and tumor response to the combination of Gleevec and Paclitaxel. Additional Cohort Objectives: + Document any relationship between C-Kit and PDGF-R expression on tumor biopsies and tumor response to Gleevec and Paclitaxel in Taxane refractory breast cancer patients. + Document any relationship between C-Kit and PDGF-R expression on tumor biopsies and tumor response to Gleevec and Paclitaxel in Taxane refractory Non-Small Cell Lung Cancer patients. Hypothesis: To determine the safety of combining these two potential anti-angiogenic agents.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 Gleevec通过对BCR-ABL，血小板衍生的生长因子受体和C-KIT激活的酪氨酸激酶途径的有效活性表现出了慢性髓样白血病（CML）和胃肠道间质肿瘤的活性。 紫杉醇通过微管对微管组装的作用和微管的稳定性对去聚合的作用具有广泛的抗肿瘤活性，从而抑制了细胞周期中期 - 移动酶的持续有丝分裂块，从而抑制细胞增殖。 先前的临床前研究表明，当其他化学疗法与Gleevec结合使用时，尚未在这种比较中评估紫杉醇。通过将宽阔的作用剂紫杉醇与新药物Gleevec相结合，我们可以观察到添加剂甚至协同作用，而没有显着继发于独立抗肿瘤机制的毒性的显着增加 具体目的： 主要目的： +确定剂量限制毒性以及Gleevec和Paclitaxel的最大耐受剂量在给患有晚期肿瘤患者的情况下。 +当组合给出时Gleevec和Paclitaxel的药代动力学表征。 次要目的： +记录用Gleevec和紫杉醇治疗的患者中的任何客观抗肿瘤反应。 +记录C-KIT和血小板衍生的生长因子受体（PDGF-R）在肿瘤活检中的表达与肿瘤对Gleevec和Paclitaxel组合的反应之间的关系。 其他队列目标： +记录肿瘤活检中C-KIT和PDGF-R表达之间的任何关系，以及紫杉烷难治性乳腺癌患者对Gleevec和紫杉醇对Gleevec和紫杉醇的反应。 +记录了肿瘤活检中C-KIT和PDGF-R表达之间的任何关系，以及紫杉烷难治性非小细胞肺癌患者中对Gleevec和Paclitaxel对Gleevec和Paclitaxel的反应。 假设：确定将这两种潜在抗血管生成剂结合起来的安全性。