The purpose of the protocol was to induce a novel radiochemotherapy with enzastaurin as first-line treatment regimen in glioblastoma: Participants with active, unmethylated MGMT promoter were treated with enzastaurin before, concomitant, and after radiotherapy to determine safety and PFS at 6 months (PFS-6) in phase II.

Inclusion Criteria:

• Present with newly diagnosed histologically proven supratentorial GBM.
• Demonstration of an unmethylated MGMT-promotor
• Participants must sign an informed consent document. Participants must be at least 18 years of age.
• Estimated life expectancy of at least 12 weeks
• Tumor tissue specimens (paraffin-embedded and/or frozen) from the GBM surgery or biopsy must be available for central pathology review and exploratory analysis of PKC-beta targets (for example, GSK3beta).
• Disease evaluated by Gd-MRI (magnetic resonance imaging) within 72 hours postoperatively
• Interval of greater than or equal to 2 and less than or equal to 4 weeks since surgery or biopsy
• ECOG Performance Status of less than or equal to 2
• Adequate organ function including the following:
• adequate bone marrow reserve: white blood cell (WBC) count greater than or equal to 3.0 X 109/L, absolute neutrophil count (ANC) greater than or equal to 1.5 X 109/L, platelet count greater than or equal to 75.0 X 109/L, and hemoglobin greater than or equal to 10.0 g/dL (greater than or equal to 6.2 mmol/L).
• Hepatic: bilirubin less than or equal to 1.5 times the upper limit of normal (X ULN), alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT) less than or equal to 2.5 X ULN, or less than or equal to 5 X ULN with liver metastases
• Renal: serum creatinine less than or equal to 1.5 X ULN
• Blood clotting: prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits
• Participants must discontinue use of enzyme-inducing antiepileptic drugs (EIAEDs) greater than or equal to 14 days prior to study enrollment. The investigator may prescribe non-EIAEDs. Participants who must begin EIAED therapy while on study will be allowed to remain on study.
• Clinically normal cardiac function without history of ischemic heart disease in the past 6 months and normal 12-lead electrocardiogram (ECG); no history of stroke

Exclusion Criteria:

• Have a prior malignancy (other than glioblastoma, or adequately treated carcinoma in situ of the cervix, or nonmelanoma skin cancer), unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence
• Unable to undergo Gd MRI
• Prior chemotherapy within the last 5 years
• Prior chemotherapy for a brain tumor
• Prior radiotherapy of the head
• Are unable to discontinue use of carbamazepine, phenobarbital, and phenytoin
• History of coagulation disorder associated with bleeding, or recurrent thrombotic events
• Are receiving concurrent administration of anticoagulant therapy
• Placement of Gliadel® wafer at surgery
• Have a serious concomitant systemic disorder (for example, active infection including HIV, or cardiac disease) - participants who are pregnant, anticipate becoming pregnant within 6 months after study participation, or are currently breast-feeding
• Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry