Phase 3
N=545
Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Methylated Gene Promoter Status
Glioblastoma
Bottom Line
View on ClinicalTrials.gov: NCT00689221 ↗Enrolled (actual)
545
Serious AEs
48.6%
Results posted
Nov 2014
Primary outcome: Primary: Overall Survival (OS) Time — 26.3; 26.3 Months — p=0.8623
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Cilengitide (Drug); Temozolomide (Drug); Radiotherapy (Radiation)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- EMD Serono
- Primary completion
- Nov 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Survival (OS) Time |
26.3; 26.3 | 0.8623 |
| SECONDARY Progression Free Survival (PFS) Time - Investigator and Independent Read |
13.5; 10.7; 10.6; 7.9 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) |
167363.2 | — |
| SECONDARY Time to Maximum Plasma Concentration (Tmax) |
1.029 | — |
| SECONDARY Area Under the Plasma Concentration Curve From Time 0 to 6 Hours (AUC [0-6]) After Dose |
295171.2 | — |
| SECONDARY European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores |
54.34; 55.43; 65.70; 67.46; 56.34; 56.34 | — |
| SECONDARY European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores |
44.49; 39.31; 12.99; 17.78; 27.45; 23.39 | — |
| SECONDARY EuroQol 5-Dimensions (EQ-5D) Questionnaire Index |
0.598; 0.623 | — |
| SECONDARY Number of Participants With Change From Baseline in Work Status at End of Study |
3; 6; 2; 1; 1; 0 | — |
| SECONDARY Number of Participants With Adverse Events (AEs), Serious AEs, Treatment-Related AEs, Treatment-Related Serious AEs, AEs Leading to Death, Treatment Related AEs Leading to Death, AEs of Grade 3 or 4 and Treatment Related AEs of Grade 3 or 4 |
261; 253; 138; 115; 229; 222 | — |
| SECONDARY Number of Participants With AEs Belonging to Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) Thromboembolic Events and Hemorrhage With NCI-CTC Toxicity Grade 3 or 4 |
35; 23; 4; 4 | — |
| SECONDARY Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) and Lab Parameters |
— | — |
Summary
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.
Eligibility Criteria
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 ( =) 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, 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 = 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
Data sourced from ClinicalTrials.gov (NCT00689221). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.