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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
545
Cilengitide 2000 milligram (mg) will be administered intravenously twice weekly over 1 hour infusion from Weeks -1 to 77 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason. If considered beneficial in the opinion of the Investigator, continuation of cilengitide treatment will be optional in subjects without disease progression and after Week 77 since start of treatment.
Temozolomide (TMZ) 75 milligram per square meter \[mg/m\^2\] will be administered intravenously once daily from Weeks 1 to 6. From Week 11 onwards, TMZ will be given as maintenance treatment at a dose of 150-200 mg/m\^2 for consecutive 5 days every 4 weeks until Week 34 or until disease progression.
Radiotherapy (RTX) at a dose of 2 gray (Gy) per fraction will be given once daily, 5 days per week from Weeks 1 to 6, total dose 60 Gy.
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Rockland, Massachusetts, United States
Please Contact the Merck KGaA Communication Center Located in
Darmstadt, Germany
Overall Survival (OS) Time
The OS time is defined as the time (in months) from randomization to death or last day known to be alive. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier.
Time frame: Time from randomization to death or last day known to be alive, reported between day of first participant randomized, that is, Sep 2008 until cut-off date, (19 Nov 2012)
Progression Free Survival (PFS) Time - Investigator and Independent Read
The PFS time is defined as the duration from randomization to either first observation of progressive disease (PD) or occurrence of death due to any cause. Investigator read is the assessment of all imaging by the treating physician at the local trial site and Independent Read is the assessment of all imaging centrally by an Independent Review Committee (IRC). Investigator's assessed progression according to MacDonald criteria and IRC by Response Assessment in Neuro-Oncology Working Group (RANO) criteria using Gadolinium-enhanced magnetic resonance imaging. Investigator and IRC read: Progression is defined as greater than 25 percent increase in the sum of the product of the largest perpendicular diameters of enhancing tumor compared to the smallest prior sum, or Worsening of an evaluable lesion(s),or Marked increase in T2/FLAIR non-enhancing lesions (IRC only) or Any new lesion
Time frame: Time from randomization to disease progression, death or last tumor assessment, reported between day of first participant randomized, that is, Sep 2008 until cut-off date, (19 Nov 2012)
Maximum Observed Plasma Concentration (Cmax)
The Cmax for cilengitide was calculated by non-compartmental analysis using the computer program WinNonlin, Version 6.2.1.
Time frame: Day 1 of Week -1
Time to Maximum Plasma Concentration (Tmax)
The Tmax for cilengitide was calculated by non-compartmental analysis using the computer program WinNonlin, Version 6.2.1.
Time frame: Day 1 of Week -1
Area Under the Plasma Concentration Curve From Time 0 to 6 Hours (AUC [0-6]) After Dose
The AUC (0-6) for cilengitide was calculated by non-compartmental analysis using the computer program WinNonlin, Version 6.2.1.
Time frame: Day 1 of Week -1
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores
The EORTC QLQ-C30 is a questionnaire including following sub-scales: global health status, functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social activity), symptom scales (fatigue, nausea and vomiting, and pain) and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhoea and financial difficulties). Scores are averaged for each scale and transformed to 0-100 scale; higher score indicates better quality of life on global health status and functional scales and worse quality of life on symptom scales and financial difficulty scale.
Time frame: Up to 50 months
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores
The QLQ-BN20 is a questionnaire specifically designed as the QLQ-C30 supplement for the evaluation of quality of life in brain tumor participants. It includes 4 multi-item sub-scales: future uncertainty, visual disorder, motor dysfunction, communication deficits, and 7 single-item scales: headaches, seizures, drowsiness, itchy skin, hair loss, weakness of legs, and bladder control. All items are rated on a 4-point Likert-type scale ('1=not at all', '2=a little', '3=quite a bit' and '4=very much'), and are linearly transformed to a 0-100 scale, with higher scores indicating more severe symptoms.
Time frame: Up to 50 months
EuroQol 5-Dimensions (EQ-5D) Questionnaire Index
The EuroQuol-5D (EQ-5D) questionnaire is a measure of health status that provides a simple descriptive profile and a single index value. The optional part of the questionnaire was not applied. The EQ-5D defines health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5 items are combined to generate health profiles. These profiles were converted to a continuous single index score using a one to one matching. The lowest possible score is -0.594 (death) and the highest is 1.00 (full health).
Time frame: Up to 50 months
Number of Participants With Change From Baseline in Work Status at End of Study
Number of participants with change from baseline in work status (working full time \[FT\], part-time \[PT\], unemployed/retired \[U/R\]) at end of study (EOS) (up to cut-off date, \[19 Nov 2012\]) was reported. For the category 'part-time', the following sub-categories were defined: part-time due to basic disease (PT1); part-time not due to basic disease (PT2); part-time reason not known (PT3).
Time frame: Baseline, End of study (up to cut-off date, [19 Nov 2012])
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
An AE is defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. Treatment-emergent AEs are the events between first dose of study drug and up to 28 days after last dose of study treatment. A Serious AE is an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. Treatment-related AEs are the AEs which are suspected to be reasonably related to the study treatment (cilengitide, or radiotherapy, or temozolomide) as per investigator assessment. The severity of AEs was assessed according to the National Cancer Institute-Common Toxicity Criteria (NCI-CTCAE) (version 3.0): Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling. Note: Death (Grade 5) was regarded as an outcome.
Time frame: Time from first dose up to 28 days after last dose of study treatment, reported between day of first participant randomized, that is, Sep 2008 until cut-off date (19 Nov 2012)
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
Thromboembolic events (standardized MedDRA query \[SMQ\]) Grade 3 or 4 AEs encompassed hemiparesis and cerebrovascular accident, pulmonary embolism, and deep vein thrombosis. Thromboembolic events (SMQ) of any grade and of Grade 3 or 4 were generally more frequent in the Cilengitide + Temozolomide/Radiotherapy group than in the Temozolomide/Radiotherapy group but were still in the expected range of this patient population The severity of AEs was assessed according to the National Cancer Institute-Common Toxicity Criteria (NCI-CTCAE) (version 3.0): Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling. Note: Death (Grade 5) was regarded as an outcome.
Time frame: Time from first dose up to 28 days after last dose of study treatment, reported between day of first participant randomized, that is, Sep 2008 until cut-off date (19 Nov 2012)
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) and Lab Parameters
Time frame: Up to 50 months
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