Effect of Radiation Therapy Plus Temozolomide Combined With Cilengitide or Cetuximab on the 1-year Overall Survival of Patients With Newly Diagnosed MGMT-promoter Unmethylated Glioblastoma

Inclusion Criteria:

1. Written informed consent
2. Newly diagnosed histologically proven supratentorial glioblastoma (World Health Organization \[WHO\] Grade IV, including glioblastoma subtypes, e.g. gliosarcoma).
3. Tumor tissue specimens from the glioblastoma surgery or open biopsy (FFPE block) must be available for MGMT gene promoter status analysis and central pathology review and must have been submitted as part of the screen procedure for the CENTRIC phase III study
4. MGMT gene promoter status determined as NOT methylated during the screen procedure for the CENTRIC phase III study
5. Males or females ≥18 years of age.
6. Interval of ≥2 weeks but ≤7 weeks after surgery or biopsy before first administration of study treatment.
7. Available post-operative Gd-MRI performed within 48 hours after surgery
8. Stable or decreasing dose of steroids for 5 days prior to randomization.
9. Eastern Cooperative Oncology Group performance score (ECOG PS) of 0-1.
10. Meets one of the following recursive partitioning analysis (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, Mini Mental State Examination \[MMSE\] ≥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 open tumor biopsy only).
11. Laboratory values

    * Absolute neutrophil count 1500/mm3.
    * Platelets 100,000/mm3.
    * Creatinin 1.5 x upper limit of normal (ULN) or creatinine clearance rate 60 mL/min.
    * Hemoglobin 10 g/dL.
    * Total bilirubin 1.5 x the ULN.
    * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 2.5 x ULN (except when attributable to anticonvulsants).
    * Alkaline phosphatase 2.5 x ULN.
    * Prothrombin time (PT) international normalized ratio (INR) and partial thromboplastin time (PTT) within normal limits.

Exclusion Criteria:

1. Prior chemotherapy within the last 5 years.
2. Prior RT of the head.
3. Receiving concurrent investigational agents or has received an investigational agent within the past 30 days prior to the first dose of Cilengitide.
4. Prior systemic anti-angiogenic therapy.
5. Placement of Gliadel® wafer at surgery.
6. Planned surgery for other diseases (e.g. dental extraction).
7. History of recent peptic ulcer disease within 6 months of enrollment.
8. 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 5 years are eligible for this study.
9. History of coagulation disorder associated with bleeding or recurrent thrombotic events.
10. Clinically manifest myocardial insufficiency or history of myocardial infarction during the past 6 months; or uncontrolled arterial hypertension.
11. Inability to undergo Gd-MRI.
12. Concurrent illness, including severe dermatological conditions or infection, which may jeopardize the ability of the subject to receive the procedures outlined in this protocol with reasonable safety.
13. Subject is pregnant or is currently breast-feeding, anticipates becoming pregnant/ impregnating their partner during the study or within 6 months after study participation, or subject does not agree to follow acceptable methods of birth control, such as hormonal contraception, intra-uterine pessary, condoms or sterilization, to avoid conception during the study and for at least 6 months after receiving the last dose of study treatment.
14. Current alcohol dependence or drug abuse.
15. Known hypersensitivity to the study treatment.
16. Legal incapacity or limited legal capacity.
17. Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
18. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such.
19. Treatment with prohibited concomitant medication as defined in Section