Enzastaurin Before and Concomitant With Radiation, Followed by Enzastaurin in Participants With Newly Diagnosed Glioblastoma

Lilly

Status and phase

Completed

Phase 2

Conditions

Glioblastoma Multiforme

Treatments

Drug: Enzastaurin 250 mg Twice Daily (BID)

Drug: Enzastaurin 500 milligram (mg) Once Daily (QD)

Study type

Interventional

Funder types

Industry

Identifiers

NCT00509821

H6Q-MC-S039 (Other Identifier)

11491

Details and patient eligibility

About

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.

Enrollment

60 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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