NABTT2111 - BMS-247550

NABTT2111 - BMS-247550

• 批准号: 7603229
• 负责人: BURTON L NABORS
• 金额: $ 0.08万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603229
• 关键词: Adult; Anticonvulsants; Biological Factors; Breast; CA-125 Antigen; Cancer Patient; Cell Line; Cervical; Clinical; Computer Retrieval of Information on Scientific Projects Database; Cytochrome P450; Development; Dose; Drug Kinetics; Enzymes; Epothilone B; Funding; Glioma; Grant; Hepatic; Institution; Malignant Glioma; Malignant neoplasm of cervix uteri; Malignant neoplasm of ovary; Maximum Tolerated Dose; Measures; Methods; Multienzyme Complexes; Paclitaxel; Patients; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Progression-Free Survivals; Rate; Recurrence; Research; Research Personnel; Resistance; Resources; Route; Safety; Source; Taxane Compound; Toxic effect; Treatment Protocols; United States National Institutes of Health; analog; base; pre-clinical; response; taxane

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. The objectives of the Dose Finding (Continual Reassessment Method (CRM)) phase of this clinical trial are 1) To determine the maximum tolerated dose of BMS-247550 when administered to adults with recurrent malignant gliomas, receiving (Group A) or not receiving (Group B) anticonvulsants known to be metabolized by the P450 hepatic enzyme complex. 2) To describe the pharmacokinetics of this route of administration, measuring BMS-247550, and determine the effects of hepatic enzyme inducing drugs, such as anticonvulsants , on the pharmacokinetics . The objectives for the Safety/Efficacy at Maximum Tolerated Dose (MTD) phase are 1) To determine the response rate of adult patients with recurrent glioma to BMS-247550 administered at the MTD. 2) To describe the toxicity associated with this regimen in adult patients with recurrent malignant gliomas. Secondary Objective a) To determine the percent of patients with 6 month progression free survival, duration of progression free survival and survival associated with this therapy in adult patients with recurrent malignant gliomas. BMS-247550 is a methyl, semi-synthetic analog of the natural product epothilone B produced by Bristol-Myers Squibb. This compound was selected for clinical development based on impressive preclinical activity against paclitaxel-sensitive and -resistant cell lines. Objective responses have been observed in patients with breast and cervical cancer; with > 50% reduction in CA125 in two of 12 patients with advanced ovarian cancer (all breast, cervical and ovary cancer patients had prior taxane therapy).

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本临床试验的剂量探索（持续重新评估方法（CRM））阶段的目的是1）确定复发性恶性胶质瘤成人患者接受（A组）或未接受（B组）已知由P450肝酶复合物代谢的抗惊厥药给药时BMS-247550的最大耐受剂量。2)描述该给药途径的药代动力学，测量BMS-247550，并确定肝酶诱导药物（如抗惊厥药）对药代动力学的影响。最大耐受剂量（MTD）阶段的安全性/疗效的目的是1）确定复发性胶质瘤成人患者对MTD BMS-247550给药的缓解率。 2)描述该方案在复发性恶性胶质瘤成人患者中的毒性。 次要目的a）确定复发性恶性胶质瘤成人患者中6个月无进展生存期的患者百分比、无进展生存期的持续时间以及与该治疗相关的生存期。BMS-247550是Bristol-Myers Squibb生产的天然产物埃坡霉素B的甲基半合成类似物。基于对紫杉醇敏感和耐药细胞系的令人印象深刻的临床前活性，选择该化合物进行临床开发。在乳腺癌和宫颈癌患者中观察到了客观反应; 12名晚期卵巢癌患者中有2名CA 125降低> 50%（所有乳腺癌、宫颈癌和卵巢癌患者既往均接受过紫杉烷治疗）。