Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Methylated Gene Promoter Status (CENTRIC)

Merck KGaA (EMD Serono)

Status and phase

Completed

Phase 3

Conditions

Glioblastoma

Treatments

Drug: Temozolomide

Radiation: Radiotherapy

Drug: Cilengitide

Study type

Interventional

Funder types

NETWORK

Industry

Identifiers

NCT00689221

2007-004344-78 (EudraCT Number)

EORTC 26071-22072

EMD 121974-011

Details and patient eligibility

About

CENTRIC is a Phase 3 clinical trial assessing efficacy and safety of the investigational integrin inhibitor, cilengitide, in combination with standard treatment versus standard treatment alone in newly diagnosed glioblastoma subjects with a methylated O6-methylguanine-deoxyribonucleic acid methyltransferase (MGMT) gene promoter in the tumor tissue.

The MGMT gene promoter is a section of deoxyribonucleic acid (DNA) that acts as a controlling element in the expression of MGMT. Methylation of the MGMT gene promoter has been found to be a predictive marker for benefit from temozolomide (TMZ) treatment.

Enrollment

545 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Tumor tissue specimens from the glioblastoma surgery or open biopsy (formalin-fixed, paraffin-embedded block; stereotactic biopsy not allowed) must be available for MGMT status analysis and central pathology review
Newly diagnosed histologically proven supratentorial glioblastoma (World Health Organization [WHO] Grade IV)
Proven methylated MGMT gene promoter methylation status
Available post-operative gadolinium-enhanced magnetic resonance imaging (Gd-MRI) performed within less than (<) 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)
Stable or decreasing dose of steroids for greater than or equal to (>=) 5 days prior to randomization
Eastern Cooperative Oncology Group performance score (ECOG PS) of 0-1
Meets 1 of the following recursive partitioning analysis (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: 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)
Other protocol defined inclusion criteria could apply

Exclusion criteria

Prior chemotherapy within the last 5 years
Prior RTX of the head
Receiving concurrent investigational agents or has received an investigational agent within the past 30 days prior to the first dose of cilengitide
Prior systemic antiangiogenic therapy
Placement of Gliadel® wafer at surgery
Inability to undergo Gd-MRI.
Planned surgery for other diseases
History of recent peptic ulcer disease (endoscopically proven gastric ulcer, duodenal ulcer, or esophageal ulcer) within 6 months of enrollment
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
History of coagulation disorder associated with bleeding or recurrent thrombotic events
Clinically manifest myocardial insufficiency (New York Heart Association [NYHA] III, IV) or history of myocardial infarction during the past 6 months; uncontrolled arterial hypertension
Other protocol defined exclusion criteria could apply