Inclusion Criteria:

• Written informed consent obtained before undergoing any study-related activities.
• Males or females 18 years of age or older who can be treated in an outpatient setting.
• Histologically proven GBM, which is recurrent or progressive following surgery or biopsy, external beam radiation therapy, and 1 previous regimen of systemic chemotherapy (Gliadel wafer therapy is not considered systemic chemotherapy). Malignancy is to be documented with a previous histopathological report.
• Subjects initially diagnosed with other conditions similar to GBM (such as anaplastic astrocytoma [AA] or low grade glioma) that subsequently progressed to histologically proven GBM and have had surgery or biopsy, external beam radiation therapy, and 1 previous regimen of systemic chemotherapy for the original diagnosis are eligible if they meet all inclusion criteria.
• GBM recurring only in the contralateral hemisphere must be histologically confirmed by biopsy. GBM recurring bilaterally does not need to be histologically confirmed by biopsy (i.e., if recurrence is ipsilateral and contralateral).
• Archived tumor tissue specimens from the GBM surgery or biopsy must be available for central pathology review and exploratory analysis of angiogenic markers (e.g. avb3 and avb5 integrins).
• Measurable disease (solid contrast-enhancing lesion ~1 cm in any dimension) evaluated by Gd MRI within 2 weeks prior to the first dose of EMD 121974.
• At least 12 weeks have elapsed since the last radiation treatment, and at least 4 weeks have elapsed since the last chemotherapy dose (at least 6 weeks for nitrosourea-containing chemotherapy) prior to the first dose of EMD 121974.
• If the subject underwent recent surgery, status must be ~2 weeks post surgery or ~1 week post biopsy, in stable condition, and maintained on a stable corticosteroid regimen for ~5 days prior to first dose of EMD 121974.
• Karnofsky Performance Score (KPS) of ≥ 70%.
• Subjects with the potential for pregnancy or impregnating their partner must agree to follow acceptable methods of birth control to avoid conception during the study and for at least 6 months after receiving the last dose of study drug.
• Women of childbearing potential must have a negative pregnancy test at screening.
• Laboratory values (within 1 week prior to the first dose of EMD 121974, except for blood count and PT/PTT, which are to be within 72 hours of the first dose): * Absolute neutrophil count ≥1500/mm 3. * Platelets ≥ 100,000/mm 3. * Creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 60 mL/min. * Hematocrit ≥ 30%. * Prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits. * Hemoglobin ≥ 10 mg/dL. * Total bilirubin ≤ 1.5 times the upper limit of normal. * Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 times above upper limit of normal.
• No more than 8 weeks have elapsed since recurrence was detected

Exclusion Criteria:

• Prior radiation therapy >66 Gray.
• Subject anticipates undergoing elective surgery, dental extraction, or invasive dental procedures.
• History of recent peptic ulcer disease (endoscopically proven gastric ulcer, duodenal ulcer, or esophageal ulcer) within 6 months of enrollment.
• History of prior malignancy. Subjects with curatively treated cervical carcinoma in situ or basal cell carcinoma of the skin, or subjects who have been free of other malignancies for ≥5 years are eligible for this study.
• History of coagulation disorder associated with bleeding or recurrent thrombotic events.
• Concurrent illness, including severe infection, which may jeopardize the ability of the subject to receive the procedures outlined in this protocol with reasonable safety.
• Subject is pregnant, anticipates becoming pregnant within 6 months after study participation, or is currently breast-feeding.
• Receiving concurrent investigational agents or has received an investigational agent within the past 30 days prior to the first dose of EMD 121974.
• Prior antiangiogenic therapy.
• Placement of Gliadel wafer at surgery for recurrence.
• Unable to undergo Gd MRI.
• Current known alcohol dependence or drug abuse.
• Requiring concomitant chemotherapy.
• Treatment with a prohibited concomitant medication.
• Known hypersensitivity to the study treatment.
• Legal incapacity or limited legal capacity.