Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Unmethylated Gene Promoter Status (CORE)

Inclusion Criteria:

1. Newly diagnosed histologically proven supratentorial GBM
2. Tumor tissue specimens from the GBM surgery or open biopsy must be available for MGMT gene promoter status analysis and central pathology review.
3. Proven unmethylated MGMT gene promoter status
4. Males or females ≥18 years of age.
5. Interval of ≥2 weeks but ≤7 weeks after surgery or biopsy before first administration of study treatment.
6. Available post-operative Gd-MRI performed within <48 hours after surgery
7. Stable or decreasing dose of steroids for ≥5 days prior to randomization.
8. ECOG PS of 0-1.

9. 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, Mini Mental State Examination [MMSE] ≥27).

   • Class V (meeting one of the following criteria:

     1. 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:

1. Prior chemotherapy within the last 5 years.
2. Prior RTX 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 (endoscopically proven gastric ulcer, duodenal ulcer, or esophageal ulcer) 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 (New York Heart Association [NYHA] III, IV) 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 infection, which may jeopardize the ability of the subject to receive the procedures outlined in this protocol with reasonable safety.
13. Subject is pregnant (positive serum beta human chorionic gonadotropin [b-HCG] test at screening) 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 pessar, 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.