CENTRIC is a Phase III clinical trial assessing efficacy and safety of the investigational integrin inhibitor, cilengitide, in combination with standard treatment versus standard treatment alone in newly diagnosed glioblastoma multiforme (GBM) patients with a methylated promoter of the methylguanine-DNA methyltransferase (MGMT) gene in the tumor tissue.

The MGMT gene promoter is a section of DNA that acts as a controlling element in the expression of MGMT. Methylation of the MGMT gene promoter has been found to be a predictive marker for benefit from temozolomide (TMZ) treatment.

• Drug: Cilengitide, Temozolomide & Radiotherapy
• Drug: Temozolomide & Radiotherapy

• Experimental: Cilengitide, Radiotherapy & Temozolomide
• Other: Temozolomide & Radiotherapy

Inclusion Criteria:

• Tumor tissue specimens from the GBM surgery or open biopsy (formalin-fixed, paraffin-embedded block; stereotactic biopsy not allowed) must be available for MGMT status analysis and central pathology review.
• Newly diagnosed histologically proven supratentorial GBM (World Health Organization [WHO] Grade IV).
• Proven methylated MGMT gene promoter methylation status.
• Available post-operative Gd-MRI performed within <48 hours after surgery (in case it was not possible to obtain a Gd-MRI within <48 hours post surgery, a Gd-MRI is to be performed prior to randomization).
• Stable or decreasing dose of steroids for ³5 days prior to randomization
• ECOG PS of 0-1.
• Meets 1 of the following RPA classifications:• Class III (Age <50 years and ECOG PS 0). Class IV (meeting one of the following criteria: a) Age <50 years and ECOG PS 1 or b) Age ≥50 years, underwent prior partial or total tumor resection, MMSE ≥27).•Class V (meeting one of the following criteria: a) Age ≥50 years and underwent prior partial or total tumor resection, MMSE <27 or b) Age ≥50 years and underwent prior tumor biopsy only).

Exclusion Criteria:

• Prior chemotherapy within the last 5 years.
• Prior RTX of the head.
• Receiving concurrent investigational agents or has received an investigational agent within the past 30 days prior to the first dose of cilengitide.
• Prior systemic antiangiogenic therapy.
• Placement of Gliadel® wafer at surgery.
• Inability to undergo Gd-MRI.
• Planned surgery for other diseases (e.g. dental extraction).
• History of recent peptic ulcer disease (endoscopically proven gastric ulcer, duodenal ulcer, or esophageal ulcer) within 6 months of enrollment.
• History of 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 ³ 5 years are eligible for this study.
• History of coagulation disorder associated with bleeding or recurrent thrombotic events.
• Clinically manifest myocardial insufficiency (NYHA III, IV) or history of myocardial infarction during the past 6 months. Uncontrolled arterial hypertension.