Enzastaurin Before and Concomitant With Radiation Therapy, Followed by Enzastaurin Maintenance Therapy in Patients With Newly Diagnosed Glioblastoma Without Methylation of the Promoter Gene of MGMT Enzyme - a Phase II Study
Inclusion Criteria:
- Present with newly diagnosed histologically proven supratentorial GBM.
- Demonstration of an unmethylated MGMT-promotor
- Patients must sign an informed consent document. Patients 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
- Patients 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. Patients 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 GliadelĀ® wafer at surgery
- Have a serious concomitant systemic disorder (for example, active infection including
HIV, or cardiac disease) - patients 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