Cilengitide for Subjects With Newly Diagnosed Glioblastoma Multiforme and Methylated MGMT Gene Promoter - A Multicenter, Open-label, Controlled Phase III Study, Testing Cilengitide in Combination With Standard Treatment (Temozolomide With Concomitant Radiation Therapy, Followed by Temozolomide Maintenance Therapy) Versus Standard Treatment Alone
1. 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.
2. Newly diagnosed histologically proven supratentorial GBM (World Health Organization
[WHO] Grade IV).
3. Proven methylated MGMT gene promoter methylation status.
4. 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).
5. Stable or decreasing dose of steroids for ³5 days prior to randomization
6. ECOG PS of 0-1.
7. 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).
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 antiangiogenic therapy.
5. Placement of Gliadel® wafer at surgery.
6. Inability to undergo Gd-MRI.
7. Planned surgery for other diseases (e.g. dental extraction).
8. History of recent peptic ulcer disease (endoscopically proven gastric ulcer, duodenal
ulcer, or esophageal ulcer) within 6 months of enrollment.
9. 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.
10. History of coagulation disorder associated with bleeding or recurrent thrombotic
11. Clinically manifest myocardial insufficiency (NYHA III, IV) or history of myocardial
infarction during the past 6 months. Uncontrolled arterial hypertension.