NABTT 0306 EMD 121974 TRIAL

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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.