Cilengitide in Subjects With Newly Diagnosed Glioblastoma Multiforme and Unmethylated MGMT Gene Promoter - a Multicenter, Open-label Phase II Study, Investigating Two Cilengitide Regimens in Combination With Standard Treatment (Temozolomide With Concomitant Radiation Therapy, Followed by Temozolomide Maintenance Therapy).
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).
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
10. Clinically manifest myocardial insufficiency (New York Heart Association [NYHA] III,
IV) or history of myocardial infarction during the past 6 months; or uncontrolled
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
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.