NABTT 0306 EMD 121974 TRIAL

这个子项目是许多利用 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。 本临床试验的目的是评估EMD 121974（西仑吉肽）每周两次1小时输注给药，同时伴随和辅助替莫唑胺与放射疗法治疗新诊断的多形性胶质母细胞瘤的安全性特征。该研究还将有助于估计新诊断的多形性胶质母细胞瘤患者接受EMD 121974同时伴随和辅助替莫唑胺与放射治疗的总生存期。次要目的包括：估计和比较用EMD 121974同时伴随和辅助替莫唑胺与放射疗法治疗的新诊断患者中低剂量治疗组和高剂量治疗组之间的总存活率。确定EMD 121974在体内给药时的毒性 与伴随的和辅助的替莫唑胺联合放射疗法。评估个体患者的分子谱，并将分子表达谱与临床结果相关联。最后，在新诊断的多形性胶质母细胞瘤中使用灌注MR表征肿瘤血容量、肿瘤血流量和渗透率，并在EMD 121974治疗期间跟踪这些参数。恶性神经胶质瘤是最致命的癌症之一。 多形性胶质母细胞瘤诊断的发病率和死亡率可归因于胶质瘤细胞的侵袭性和与该肿瘤相关的稳健血管生长。EMD 121974具有抗血管生成特性。它是一种有效的和选择性的α v，β 3和α v，β 5整联蛋白受体拮抗剂，阻断α v-整联蛋白介导的细胞附着和迁移。它已被证明在各种体内系统中抑制肿瘤生长，包括鸡绒毛尿囊膜模型、裸鼠和接种人肿瘤细胞的严重联合免疫缺陷小鼠。此外，α v、β 3整联蛋白在GBM中表达并在肿瘤生长中起作用。它已被证明在 体外研究表明，这些整联蛋白的抑制剂不仅抑制血管生成，而且表现出有效的抗有丝分裂作用。EMD 121974不仅通过其抗血管生成作用，而且通过直接抑制肿瘤生长，具有影响GBM肿瘤生长的潜力。本临床试验将最多入组94例患者，每组约47例患者，患者将接受每周两次、每次1小时的研究药物输注，直至出现剂量限制性毒性或重大事件或符合其他停止治疗的标准。

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 this clinical trial are to assess the safety profile of EMD 121974 (cilengitide) when administered as a one-hour infusion twice weekly concurrently with concomitant and adjuvant temozolomide with radiation therapy for newly diagnosed glioblastoma multiforme. The study also will help to estimate the overall survival in newly diagnosed patients with glioblastoma multiforme treated with EMD 121974 concurrently with concomitant and adjuvant temozolomide with radiation therapy. Secondary objectives include: estimating and comparing the overall survival between a low dose treatment group and a high dose treatment group in newly diagnosed patients treated with EMD 121974 concurrently with concomitant and adjuvant temozolomide with radiation therapy. Determining the toxicity of EMD 121974 when it is administered in conjunction with concomitant and adjuvant temozolomide with radiation therapy. Evaluating the molecular profile of individual patients and correlate molecular expression profiles with clinical outcomes. And lastly to characterize tumor blood volume, tumor blood flow, and permeability ratios using perfusion MR in newly diagnosed glioblastoma multiforme and follow these parameters during treatment with EMD 121974. Malignant gliomas are among the deadliest form of cancer. The morbidity and mortality surrounding the diagnosis of glioblastoma multiforme can be attributed to the invasiveness of glioma cells and robust blood vessel growth associated with this tumor. EMD 121974 has an antiangiogenic property. It is a potent and selective alpha v, beta 3 and alpha v, beta 5 integrin receptor antagonist that blocks alpha v-integrin-mediated cell attachment and migration. It has been shown to inhibit tumor growth in various in vivo systems including chicken chorioallantoic membrane model, nude mice, and severe combined immunodeficiency mice inoculated with human tumor cells. In addition, alpha v, beta 3 integrins are expressed in GBM and play a role in tumor growth. It has been shown in in vitro studies that inhibitors of these integrins not only inhibit angiogenesis, but also exhibit potent antimitotic effects. EMD 121974 has the potential to impact GBM tumor growth not only by its antiangiogenic effect, but also by direct inhibition of tumor growth. This clinical trial will enroll a maximum of 94 patients, approximately 47 patients in each arm. The patients will receive a twice weekly, one hour infusion of the study drug until they experience a dose-limiting toxicity or major event or meet other criteria for going off treatment.