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

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ClinicalTrials.gov Identifier: NCT00689221
Recruitment Status : Completed
First Posted : June 3, 2008
Results First Posted : November 4, 2014
Last Update Posted : November 4, 2014
Sponsor:
Collaborators:
European Organisation for Research and Treatment of Cancer - EORTC
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Glioblastoma
Interventions Drug: Cilengitide
Drug: Temozolomide
Radiation: Radiotherapy
Enrollment 545
Recruitment Details First/last participant (informed consent): Sep 2008/Aug 2011. Clinical data cut-off: 19 Nov 2012, Study completion date: Aug 2013.
Pre-assignment Details Enrolled: 3471 screened for eligibility; 2926 excluded (mainly due to unmethylated O6-methylguanine-DNA methyltransferase status and non-fulfillment of inclusion or exclusion criteria), 545 participants randomized.
Arm/Group Title Cilengitide + Temozolomide + Radiotherapy Temozolomide + Radiotherapy
Hide Arm/Group Description Cilengitide 2000 milligram (mg) twice weekly over 1 hour intravenous infusion from Weeks -1 to 77, Temozolomide (TMZ) 75 milligram per square meter [mg/m^2] intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and radiotherapy (RTX) at a dose of 2 Gray (Gy) per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason. Continuation of cilengitide treatment after Week 77 was optional in participants without disease progression, If considered beneficial in the opinion of the Investigator. TMZ 75 mg/m^2 administered intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and RTX at a dose of 2 Gy per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason.
Period Title: Overall Study
Started 272 273
Completed 233 237
Not Completed 39 36
Reason Not Completed
Ongoing at cut-off date             39             36
Arm/Group Title Cilengitide + Temozolomide + Radiotherapy Temozolomide + Radiotherapy Total
Hide Arm/Group Description Cilengitide 2000 milligram (mg) twice weekly over 1 hour intravenous infusion from Weeks -1 to 77, Temozolomide (TMZ) 75 milligram per square meter [mg/m^2] intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and radiotherapy (RTX) at a dose of 2 Gray (Gy) per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason. Continuation of cilengitide treatment after Week 77 was optional in participants without disease progression, If considered beneficial in the opinion of the Investigator. TMZ 75 mg/m^2 administered intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and RTX at a dose of 2 Gy per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason. Total of all reporting groups
Overall Number of Baseline Participants 272 273 545
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population included all the participants who were randomized to study treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 272 participants 273 participants 545 participants
56.8  (11.00) 56.0  (10.97) 56.4  (10.98)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 272 participants 273 participants 545 participants
Female
124
  45.6%
130
  47.6%
254
  46.6%
Male
148
  54.4%
143
  52.4%
291
  53.4%
1.Primary Outcome
Title Overall Survival (OS) Time
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all the participants who were randomized to study treatment.
Arm/Group Title Cilengitide + Temozolomide + Radiotherapy Temozolomide + Radiotherapy
Hide Arm/Group Description:
Cilengitide 2000 milligram (mg) twice weekly over 1 hour intravenous infusion from Weeks -1 to 77, Temozolomide (TMZ) 75 milligram per square meter [mg/m^2] intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and radiotherapy (RTX) at a dose of 2 Gray (Gy) per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason. Continuation of cilengitide treatment after Week 77 was optional in participants without disease progression, If considered beneficial in the opinion of the Investigator.
TMZ 75 mg/m^2 administered intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and RTX at a dose of 2 Gy per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason.
Overall Number of Participants Analyzed 272 273
Median (95% Confidence Interval)
Unit of Measure: Months
26.3
(23.8 to 28.8)
26.3
(23.9 to 34.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cilengitide + Temozolomide + Radiotherapy, Temozolomide + Radiotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8623
Comments P-value is not adjusted for multiple testing.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.021
Confidence Interval (2-Sided) 95%
0.808 to 1.291
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Progression Free Survival (PFS) Time - Investigator and Independent Read
Hide Description

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)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all the participants who were randomized to study treatment.
Arm/Group Title Cilengitide + Temozolomide + Radiotherapy Temozolomide + Radiotherapy
Hide Arm/Group Description:
Cilengitide 2000 milligram (mg) twice weekly over 1 hour intravenous infusion from Weeks -1 to 77, Temozolomide (TMZ) 75 milligram per square meter [mg/m^2] intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and radiotherapy (RTX) at a dose of 2 Gray (Gy) per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason. Continuation of cilengitide treatment after Week 77 was optional in participants without disease progression, If considered beneficial in the opinion of the Investigator.
TMZ 75 mg/m^2 administered intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and RTX at a dose of 2 Gy per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason.
Overall Number of Participants Analyzed 272 273
Median (95% Confidence Interval)
Unit of Measure: Months
PFS Time: Investigator read
13.5
(10.8 to 15.9)
10.7
(8.1 to 13.3)
PFS Time: Independent read
10.6
(8.2 to 13.4)
7.9
(5.9 to 12.5)
3.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants of "Cilengitide + Temozolomide + Radiotherapy" group who received at least 1 cilengitide dose with plasma concentration data available on Day 1 of Week -1.
Arm/Group Title Cilengitide + Temozolomide + Radiotherapy
Hide Arm/Group Description:
Cilengitide 2000 milligram (mg) twice weekly over 1 hour intravenous infusion from Weeks -1 to 77, Temozolomide (TMZ) 75 milligram per square meter [mg/m^2] intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and radiotherapy (RTX) at a dose of 2 Gray (Gy) per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason. Continuation of cilengitide treatment after Week 77 was optional in participants without disease progression, If considered beneficial in the opinion of the Investigator.
Overall Number of Participants Analyzed 38
Mean (Standard Deviation)
Unit of Measure: nanogram per milliliter (ng/mL)
167363.2  (368301.11)
4.Secondary Outcome
Title Time to Maximum Plasma Concentration (Tmax)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants of "Cilengitide + Temozolomide + Radiotherapy" group who received at least 1 cilengitide dose with plasma concentration data available on Day 1 of Week -1.
Arm/Group Title Cilengitide + Temozolomide + Radiotherapy
Hide Arm/Group Description:
Cilengitide 2000 milligram (mg) twice weekly over 1 hour intravenous infusion from Weeks -1 to 77, Temozolomide (TMZ) 75 milligram per square meter [mg/m^2] intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and radiotherapy (RTX) at a dose of 2 Gray (Gy) per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason. Continuation of cilengitide treatment after Week 77 was optional in participants without disease progression, If considered beneficial in the opinion of the Investigator.
Overall Number of Participants Analyzed 38
Mean (Standard Deviation)
Unit of Measure: hours
1.029  (0.401)
5.Secondary Outcome
Title Area Under the Plasma Concentration Curve From Time 0 to 6 Hours (AUC [0-6]) After Dose
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants of "Cilengitide + Temozolomide + Radiotherapy" group who received at least 1 cilengitide dose with plasma concentration data available on Day 1 of Week -1. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Cilengitide + Temozolomide + Radiotherapy
Hide Arm/Group Description:
Cilengitide 2000 milligram (mg) twice weekly over 1 hour intravenous infusion from Weeks -1 to 77, Temozolomide (TMZ) 75 milligram per square meter [mg/m^2] intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and radiotherapy (RTX) at a dose of 2 Gray (Gy) per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason. Continuation of cilengitide treatment after Week 77 was optional in participants without disease progression, If considered beneficial in the opinion of the Investigator.
Overall Number of Participants Analyzed 37
Mean (Standard Deviation)
Unit of Measure: hour*ng/mL
295171.2  (198050.62)
6.Secondary Outcome
Title European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all the participants who were randomized to study treatment. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure and 'n' signifies those participants who were evaluable for the specified category.
Arm/Group Title Cilengitide + Temozolomide + Radiotherapy Temozolomide + Radiotherapy
Hide Arm/Group Description:
Cilengitide 2000 milligram (mg) twice weekly over 1 hour intravenous infusion from Weeks -1 to 77, Temozolomide (TMZ) 75 milligram per square meter [mg/m^2] intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and radiotherapy (RTX) at a dose of 2 Gray (Gy) per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason. Continuation of cilengitide treatment after Week 77 was optional in participants without disease progression, If considered beneficial in the opinion of the Investigator.
TMZ 75 mg/m^2 administered intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and RTX at a dose of 2 Gy per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason.
Overall Number of Participants Analyzed 71 93
Mean (Standard Deviation)
Unit of Measure: units on a scale
Global Health Status (n=71, 92) 54.34  (25.58) 55.43  (27.02)
Physical Functioning (n=71, 92) 65.70  (33.01) 67.46  (31.19)
Role Functioning (n=71, 92) 56.34  (37.31) 56.34  (35.19)
Emotional Functioning (n=71, 93) 67.49  (30.58) 67.00  (27.29)
Cognitive Functioning (n=70, 93) 64.05  (29.16) 65.41  (31.40)
Social Activity (n=71, 93) 56.34  (36.77) 62.72  (35.73)
Fatigue (n=71, 92) 44.37  (33.07) 39.73  (29.93)
Nausea and Vomiting (n=71, 93) 10.33  (20.77) 7.71  (16.03)
Pain (n=71, 93) 22.30  (29.40) 24.37  (28.93)
Dyspnoea (n=71, 92) 15.96  (28.09) 13.04  (22.62)
Insomnia (n=71, 91) 20.66  (30.01) 20.51  (26.65)
Appetite Loss (n=71, 92) 21.13  (30.47) 15.94  (28.59)
Constipation (n=71, 93) 18.78  (28.02) 13.98  (25.69)
Diarrhoea (n=70, 92) 6.67  (18.48) 4.35  (13.28)
Financial Difficulties (n=71, 93) 27.23  (31.53) 22.94  (31.46)
7.Secondary Outcome
Title European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all the participants who were randomized to study treatment. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure and 'n' signifies those participants who were evaluable for the specified category.
Arm/Group Title Cilengitide + Temozolomide + Radiotherapy Temozolomide + Radiotherapy
Hide Arm/Group Description:
Cilengitide 2000 milligram (mg) twice weekly over 1 hour intravenous infusion from Weeks -1 to 77, Temozolomide (TMZ) 75 milligram per square meter [mg/m^2] intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and radiotherapy (RTX) at a dose of 2 Gray (Gy) per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason. Continuation of cilengitide treatment after Week 77 was optional in participants without disease progression, If considered beneficial in the opinion of the Investigator.
TMZ 75 mg/m^2 administered intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and RTX at a dose of 2 Gy per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason.
Overall Number of Participants Analyzed 68 87
Mean (Standard Deviation)
Unit of Measure: units on a scale
Future Uncertainty (n=68, 86) 44.49  (29.70) 39.31  (30.24)
Visual Disorder (n=68, 85) 12.99  (20.24) 17.78  (23.77)
Motor Dysfunction (n=68, 86) 27.45  (30.62) 23.39  (25.95)
Communication Deficit (n=68, 86) 26.14  (28.59) 19.96  (27.89)
Headaches (n=68, 86) 25.98  (32.50) 21.71  (26.45)
Seizures (n=68, 87) 9.31  (22.93) 8.05  (20.94)
Drowsiness (n=66, 87) 38.38  (33.71) 35.25  (31.07)
Itchy Skin (n=68, 86) 9.80  (20.00) 13.57  (24.72)
Hair Loss (n=66, 86) 13.13  (22.55) 15.12  (26.40)
Weakness of Legs (n=67, 85) 24.38  (34.12) 20.39  (28.68)
Bladder Control (n=67, 85) 19.40  (29.67) 10.20  (21.22)
8.Secondary Outcome
Title EuroQol 5-Dimensions (EQ-5D) Questionnaire Index
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all the participants who were randomized to study treatment. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Cilengitide + Temozolomide + Radiotherapy Temozolomide + Radiotherapy
Hide Arm/Group Description:
Cilengitide 2000 milligram (mg) twice weekly over 1 hour intravenous infusion from Weeks -1 to 77, Temozolomide (TMZ) 75 milligram per square meter [mg/m^2] intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and radiotherapy (RTX) at a dose of 2 Gray (Gy) per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason. Continuation of cilengitide treatment after Week 77 was optional in participants without disease progression, If considered beneficial in the opinion of the Investigator.
TMZ 75 mg/m^2 administered intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and RTX at a dose of 2 Gy per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason.
Overall Number of Participants Analyzed 69 90
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.598  (0.43) 0.623  (0.36)
9.Secondary Outcome
Title Number of Participants With Change From Baseline in Work Status at End of Study
Hide Description 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])
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all the participants who received any dose of study treatment that is Cilengitide, Temozolomide or Radiotherapy. According to trial design safety data in trial arms (Cilengitide vs Control) were collected based on different visit frequency and different safety surveillance period.
Arm/Group Title Cilengitide + Temozolomide + Radiotherapy Temozolomide + Radiotherapy
Hide Arm/Group Description:
Cilengitide 2000 milligram (mg) twice weekly over 1 hour intravenous infusion from Weeks -1 to 77, Temozolomide (TMZ) 75 milligram per square meter [mg/m^2] intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and radiotherapy (RTX) at a dose of 2 Gray (Gy) per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason. Continuation of cilengitide treatment after Week 77 was optional in participants without disease progression, If considered beneficial in the opinion of the Investigator.
TMZ 75 mg/m^2 administered intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and RTX at a dose of 2 Gy per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason.
Overall Number of Participants Analyzed 263 258
Measure Type: Number
Unit of Measure: participants
Baseline: FT, EOS: FT 3 6
Baseline: FT, EOS: PT1 2 1
Baseline: FT, EOS: PT2 1 0
Baseline: FT, EOS: PT3 0 0
Baseline: FT, EOS: U/R 24 22
Baseline: PT1, EOS: FT 3 2
Baseline: PT1, EOS: PT1 3 1
Baseline: PT1, EOS: PT2 0 0
Baseline: PT1, EOS: PT3 0 0
Baseline: PT1, EOS: U/R 9 12
Baseline: PT2, EOS: FT 0 1
Baseline: PT2, EOS: PT1 0 0
Baseline: PT2, EOS: PT2 0 0
Baseline: PT2, EOS: PT3 1 0
Baseline: PT2, EOS: U/R 5 4
Baseline: PT3, EOS: FT 0 0
Baseline: PT3, EOS: PT1 0 0
Baseline: PT3, EOS: PT2 0 0
Baseline: PT3, EOS: PT3 0 0
Baseline: PT3, EOS: U/R 0 0
Baseline: U/R, EOS: FT 5 8
Baseline: U/R, EOS: PT1 5 7
Baseline: U/R, EOS: PT2 1 1
Baseline: U/R, EOS: PT3 0 0
Baseline: U/R, EOS: U/R 199 191
Baseline: Missing, EOS: FT 0 0
Baseline: Missing, EOS: PT1 0 0
Baseline: Missing, EOS: PT2 0 0
Baseline: Missing, EOS: PT3 0 0
Baseline: Missing, EOS: U/R 1 1
Baseline: Missing, EOS: Missing 1 1
10.Secondary Outcome
Title 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
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all the participants who received any dose of study treatment that is Cilengitide, Temozolomide or Radiotherapy. According to trial design safety data in trial arms (Cilengitide vs Control) were collected based on different visit frequency and different safety surveillance period.
Arm/Group Title Cilengitide + Temozolomide + Radiotherapy Temozolomide + Radiotherapy
Hide Arm/Group Description:
Cilengitide 2000 milligram (mg) twice weekly over 1 hour intravenous infusion from Weeks -1 to 77, Temozolomide (TMZ) 75 milligram per square meter [mg/m^2] intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and radiotherapy (RTX) at a dose of 2 Gray (Gy) per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason. Continuation of cilengitide treatment after Week 77 was optional in participants without disease progression, If considered beneficial in the opinion of the Investigator.
TMZ 75 mg/m^2 administered intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and RTX at a dose of 2 Gy per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason.
Overall Number of Participants Analyzed 263 258
Measure Type: Number
Unit of Measure: Participants
AEs 261 253
Serious AEs 138 115
Treatment-related AEs 229 222
Treatment-Related Serious AEs 55 47
AEs leading to death 11 9
Treatment-related AEs leading to death 3 3
AEs with NCI-CTC toxicity Grade 3 or 4 169 158
Treatment-related AEs of Grade 3 or 4 100 101
11.Secondary Outcome
Title 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
Hide Description 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)
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Hide Analysis Population Description
Safety population included all the participants who received any dose of study treatment that is Cilengitide, Temozolomide or Radiotherapy. According to trial design safety data in trial arms (Cilengitide vs Control) were collected based on different visit frequency and different safety surveillance period.
Arm/Group Title Cilengitide + Temozolomide + Radiotherapy Temozolomide + Radiotherapy
Hide Arm/Group Description:
Cilengitide 2000 milligram (mg) twice weekly over 1 hour intravenous infusion from Weeks -1 to 77, Temozolomide (TMZ) 75 milligram per square meter [mg/m^2] intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and radiotherapy (RTX) at a dose of 2 Gray (Gy) per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason. Continuation of cilengitide treatment after Week 77 was optional in participants without disease progression, If considered beneficial in the opinion of the Investigator.
TMZ 75 mg/m^2 administered intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and RTX at a dose of 2 Gy per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason.
Overall Number of Participants Analyzed 263 258
Measure Type: Number
Unit of Measure: Participants
SMQ:Thromboembolic events 35 23
SMQ: Hemorrhage 4 4
12.Secondary Outcome
Title Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) and Lab Parameters
Hide Description [Not Specified]
Time Frame Up to 50 months
Hide Outcome Measure Data
Hide Analysis Population Description
Any clinically significant abnormal ECG and lab finding was planned to be reported as AE only so they have been captured in the below mentioned adverse event section.
Arm/Group Title Cilengitide + Temozolomide + Radiotherapy Temozolomide + Radiotherapy
Hide Arm/Group Description:
Cilengitide 2000 milligram (mg) twice weekly over 1 hour intravenous infusion from Weeks -1 to 77, Temozolomide (TMZ) 75 milligram per square meter [mg/m^2] intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and radiotherapy (RTX) at a dose of 2 Gray (Gy) per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason. Continuation of cilengitide treatment after Week 77 was optional in participants without disease progression, If considered beneficial in the opinion of the Investigator.
TMZ 75 mg/m^2 administered intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and RTX at a dose of 2 Gy per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
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)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cilengitide + Temozolomide + Radiotherapy Temozolomide + Radiotherapy
Hide Arm/Group Description Cilengitide 2000 milligram (mg) twice weekly over 1 hour intravenous infusion from Weeks -1 to 77, Temozolomide (TMZ) 75 milligram per square meter [mg/m^2] intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and radiotherapy (RTX) at a dose of 2 gray (Gy) per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason. Continuation of cilengitide treatment after Week 77 will be optional in participants without disease progression, If cilengitide treatment considered beneficial in the opinion of the Investigator, TMZ 75 mg/m^2 administered intravenously once daily from Weeks 1 to 6, from Week 11 onward, TMZ was given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 and RTX at a dose of 2 Gy per fraction once daily, 5 days per week from Weeks 1 to 6 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason.
All-Cause Mortality
Cilengitide + Temozolomide + Radiotherapy Temozolomide + Radiotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Cilengitide + Temozolomide + Radiotherapy Temozolomide + Radiotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   138/263 (52.47%)   115/258 (44.57%) 
Blood and lymphatic system disorders     
THROMBOCYTOPENIA * 1  16/263 (6.08%)  24/258 (9.30%) 
NEUTROPENIA * 1  6/263 (2.28%)  11/258 (4.26%) 
LEUKOPENIA * 1  4/263 (1.52%)  10/258 (3.88%) 
ANAEMIA * 1  2/263 (0.76%)  2/258 (0.78%) 
PANCYTOPENIA * 1  1/263 (0.38%)  2/258 (0.78%) 
LYMPHOPENIA * 1  1/263 (0.38%)  1/258 (0.39%) 
DISSEMINATED INTRAVASCULAR COAGULATION * 1  0/263 (0.00%)  1/258 (0.39%) 
FEBRILE BONE MARROW APLASIA * 1  0/263 (0.00%)  1/258 (0.39%) 
FEBRILE NEUTROPENIA * 1  1/263 (0.38%)  0/258 (0.00%) 
HAEMATOTOXICITY * 1  0/263 (0.00%)  1/258 (0.39%) 
Cardiac disorders     
ATRIAL FIBRILLATION * 1  1/263 (0.38%)  1/258 (0.39%) 
ACUTE MYOCARDIAL INFARCTION * 1  0/263 (0.00%)  1/258 (0.39%) 
CARDIAC FAILURE * 1  0/263 (0.00%)  1/258 (0.39%) 
CORONARY ARTERY THROMBOSIS * 1  0/263 (0.00%)  1/258 (0.39%) 
MYOCARDIAL ISCHAEMIA * 1  1/263 (0.38%)  0/258 (0.00%) 
Ear and labyrinth disorders     
VERTIGO * 1  1/263 (0.38%)  1/258 (0.39%) 
Endocrine disorders     
ADRENAL INSUFFICIENCY * 1  0/263 (0.00%)  1/258 (0.39%) 
INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION * 1  0/263 (0.00%)  1/258 (0.39%) 
Gastrointestinal disorders     
VOMITING * 1  3/263 (1.14%)  4/258 (1.55%) 
NAUSEA * 1  2/263 (0.76%)  2/258 (0.78%) 
ABDOMINAL PAIN * 1  1/263 (0.38%)  2/258 (0.78%) 
CONSTIPATION * 1  2/263 (0.76%)  0/258 (0.00%) 
DYSPHAGIA * 1  1/263 (0.38%)  1/258 (0.39%) 
ENTERITIS * 1  2/263 (0.76%)  0/258 (0.00%) 
UPPER GASTROINTESTINAL HAEMORRHAGE * 1  1/263 (0.38%)  1/258 (0.39%) 
ABDOMINAL PAIN UPPER * 1  0/263 (0.00%)  1/258 (0.39%) 
COLITIS * 1  0/263 (0.00%)  1/258 (0.39%) 
DIARRHOEA * 1  1/263 (0.38%)  0/258 (0.00%) 
GASTRIC DISORDER * 1  1/263 (0.38%)  0/258 (0.00%) 
General disorders     
PYREXIA * 1  4/263 (1.52%)  3/258 (1.16%) 
ASTHENIA * 1  5/263 (1.90%)  1/258 (0.39%) 
FATIGUE * 1  4/263 (1.52%)  1/258 (0.39%) 
GENERAL PHYSICAL HEALTH DETERIORATION * 1  2/263 (0.76%)  3/258 (1.16%) 
DISEASE PROGRESSION * 1  4/263 (1.52%)  0/258 (0.00%) 
DEVICE MALFUNCTION * 1  1/263 (0.38%)  0/258 (0.00%) 
CHEST PAIN * 1  1/263 (0.38%)  0/258 (0.00%) 
GAIT DISTURBANCE * 1  1/263 (0.38%)  0/258 (0.00%) 
PAIN * 1  0/263 (0.00%)  1/258 (0.39%) 
Hepatobiliary disorders     
HEPATIC FAILURE * 1  0/263 (0.00%)  2/258 (0.78%) 
CHOLECYSTITIS * 1  0/263 (0.00%)  1/258 (0.39%) 
DRUG-INDUCED LIVER INJURY * 1  1/263 (0.38%)  0/258 (0.00%) 
HEPATIC STEATOSIS * 1  1/263 (0.38%)  0/258 (0.00%) 
Immune system disorders     
DRUG HYPERSENSITIVITY * 1  1/263 (0.38%)  0/258 (0.00%) 
HYPERSENSITIVITY * 1  1/263 (0.38%)  0/258 (0.00%) 
Infections and infestations     
PNEUMONIA * 1  9/263 (3.42%)  7/258 (2.71%) 
URINARY TRACT INFECTION * 1  2/263 (0.76%)  4/258 (1.55%) 
LOWER RESPIRATORY TRACT INFECTION * 1  3/263 (1.14%)  0/258 (0.00%) 
CELLULITIS * 1  1/263 (0.38%)  1/258 (0.39%) 
GASTROENTERITIS * 1  1/263 (0.38%)  1/258 (0.39%) 
H1N1 INFLUENZA * 1  1/263 (0.38%)  1/258 (0.39%) 
POSTOPERATIVE WOUND INFECTION * 1  1/263 (0.38%)  1/258 (0.39%) 
SEPSIS * 1  2/263 (0.76%)  0/258 (0.00%) 
SEPTIC SHOCK * 1  0/263 (0.00%)  2/258 (0.78%) 
WOUND INFECTION * 1  2/263 (0.76%)  0/258 (0.00%) 
NECROTISING FASCIITIS * 1  0/263 (0.00%)  1/258 (0.39%) 
WOUND ABSCESS * 1  1/263 (0.38%)  0/258 (0.00%) 
APPENDICITIS * 1  1/263 (0.38%)  0/258 (0.00%) 
BACTERIAL INFECTION * 1  1/263 (0.38%)  0/258 (0.00%) 
BRAIN ABSCESS * 1  0/263 (0.00%)  1/258 (0.39%) 
BRONCHITIS * 1  1/263 (0.38%)  0/258 (0.00%) 
BRONCHOPNEUMONIA * 1  1/263 (0.38%)  0/258 (0.00%) 
DEVICE RELATED SEPSIS * 1  1/263 (0.38%)  0/258 (0.00%) 
EPIGLOTTITIS * 1  1/263 (0.38%)  0/258 (0.00%) 
ESCHERICHIA URINARY TRACT INFECTION * 1  1/263 (0.38%)  0/258 (0.00%) 
HERPES ZOSTER * 1  1/263 (0.38%)  0/258 (0.00%) 
INFLUENZA * 1  0/263 (0.00%)  1/258 (0.39%) 
MENINGITIS * 1  0/263 (0.00%)  1/258 (0.39%) 
ORAL CANDIDIASIS * 1  1/263 (0.38%)  0/258 (0.00%) 
OSTEOMYELITIS * 1  1/263 (0.38%)  0/258 (0.00%) 
PYELONEPHRITIS ACUTE * 1  0/263 (0.00%)  1/258 (0.39%) 
SKIN INFECTION * 1  1/263 (0.38%)  0/258 (0.00%) 
SUBCUTANEOUS ABSCESS * 1  0/263 (0.00%)  1/258 (0.39%) 
Injury, poisoning and procedural complications     
FALL * 1  1/263 (0.38%)  2/258 (0.78%) 
FACIAL BONES FRACTURE * 1  0/263 (0.00%)  1/258 (0.39%) 
FRACTURE * 1  1/263 (0.38%)  0/258 (0.00%) 
LIMB INJURY * 1  0/263 (0.00%)  1/258 (0.39%) 
OPEN WOUND * 1  1/263 (0.38%)  0/258 (0.00%) 
OVERDOSE * 1  0/263 (0.00%)  1/258 (0.39%) 
POST PROCEDURAL OEDEMA * 1  0/263 (0.00%)  1/258 (0.39%) 
POSTOPERATIVE WOUND COMPLICATION * 1  1/263 (0.38%)  0/258 (0.00%) 
RADIATION INJURY * 1  0/263 (0.00%)  1/258 (0.39%) 
RADIATION NECROSIS * 1  1/263 (0.38%)  0/258 (0.00%) 
RADIUS FRACTURE * 1  1/263 (0.38%)  0/258 (0.00%) 
THORACIC VERTEBRAL FRACTURE * 1  0/263 (0.00%)  1/258 (0.39%) 
Investigations     
LYMPHOCYTE COUNT DECREASED * 1  2/263 (0.76%)  1/258 (0.39%) 
PLATELET COUNT DECREASED * 1  2/263 (0.76%)  1/258 (0.39%) 
BLOOD URIC ACID INCREASED * 1  1/263 (0.38%)  0/258 (0.00%) 
ELECTROCARDIOGRAM QT PROLONGED * 1  1/263 (0.38%)  0/258 (0.00%) 
FIBRIN D DIMER INCREASED * 1  1/263 (0.38%)  0/258 (0.00%) 
NEUTROPHIL COUNT DECREASED * 1  1/263 (0.38%)  0/258 (0.00%) 
TRANSAMINASES INCREASED * 1  1/263 (0.38%)  0/258 (0.00%) 
Metabolism and nutrition disorders     
DEHYDRATION * 1  1/263 (0.38%)  2/258 (0.78%) 
HYPONATRAEMIA * 1  1/263 (0.38%)  1/258 (0.39%) 
DECREASED APPETITE * 1  1/263 (0.38%)  0/258 (0.00%) 
TYPE 2 DIABETES MELLITUS * 1  1/263 (0.38%)  0/258 (0.00%) 
HYPERGLYCAEMIA * 1  0/263 (0.00%)  1/258 (0.39%) 
HYPERURICAEMIA * 1  1/263 (0.38%)  0/258 (0.00%) 
HYPOCALCAEMIA * 1  1/263 (0.38%)  0/258 (0.00%) 
HYPOGLYCAEMIA * 1  1/263 (0.38%)  0/258 (0.00%) 
Musculoskeletal and connective tissue disorders     
MUSCULAR WEAKNESS * 1  1/263 (0.38%)  2/258 (0.78%) 
BACK PAIN * 1  0/263 (0.00%)  1/258 (0.39%) 
MUSCLE SPASMS * 1  1/263 (0.38%)  0/258 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
BASAL CELL CARCINOMA * 1  1/263 (0.38%)  0/258 (0.00%) 
GLIOBLASTOMA * 1  0/263 (0.00%)  1/258 (0.39%) 
INTRACRANIAL TUMOUR HAEMORRHAGE * 1  1/263 (0.38%)  0/258 (0.00%) 
METASTASES TO MENINGES * 1  0/263 (0.00%)  1/258 (0.39%) 
NEOPLASM RECURRENCE * 1  1/263 (0.38%)  0/258 (0.00%) 
NEURILEMMOMA * 1  1/263 (0.38%)  0/258 (0.00%) 
PANCREATIC CARCINOMA * 1  1/263 (0.38%)  0/258 (0.00%) 
SMALL CELL LUNG CANCER STAGE UNSPECIFIED * 1  0/263 (0.00%)  1/258 (0.39%) 
THYROID CANCER * 1  1/263 (0.38%)  0/258 (0.00%) 
TUMOUR HAEMORRHAGE * 1  1/263 (0.38%)  0/258 (0.00%) 
Nervous system disorders     
CONVULSION * 1  20/263 (7.60%)  14/258 (5.43%) 
HEMIPARESIS * 1  12/263 (4.56%)  1/258 (0.39%) 
BRAIN OEDEMA * 1  5/263 (1.90%)  5/258 (1.94%) 
EPILEPSY * 1  6/263 (2.28%)  3/258 (1.16%) 
GRAND MAL CONVULSION * 1  5/263 (1.90%)  3/258 (1.16%) 
HEADACHE * 1  5/263 (1.90%)  1/258 (0.39%) 
PARTIAL SEIZURES * 1  4/263 (1.52%)  2/258 (0.78%) 
STATUS EPILEPTICUS * 1  4/263 (1.52%)  1/258 (0.39%) 
COGNITIVE DISORDER * 1  3/263 (1.14%)  1/258 (0.39%) 
DIZZINESS * 1  3/263 (1.14%)  1/258 (0.39%) 
SOMNOLENCE * 1  3/263 (1.14%)  1/258 (0.39%) 
ATAXIA * 1  2/263 (0.76%)  1/258 (0.39%) 
CEREBROVASCULAR ACCIDENT * 1  2/263 (0.76%)  0/258 (0.00%) 
INTRACRANIAL PRESSURE INCREASED * 1  2/263 (0.76%)  0/258 (0.00%) 
PERIPHERAL MOTOR NEUROPATHY * 1  2/263 (0.76%)  0/258 (0.00%) 
APHASIA * 1  1/263 (0.38%)  1/258 (0.39%) 
CEREBRAL ISCHAEMIA * 1  1/263 (0.38%)  1/258 (0.39%) 
SPEECH DISORDER * 1  2/263 (0.76%)  0/258 (0.00%) 
DEPRESSED LEVEL OF CONSCIOUSNESS * 1  1/263 (0.38%)  0/258 (0.00%) 
PERIPHERAL SENSORY NEUROPATHY * 1  1/263 (0.38%)  0/258 (0.00%) 
BRAIN INJURY * 1  1/263 (0.38%)  0/258 (0.00%) 
CENTRAL NERVOUS SYSTEM NECROSIS * 1  1/263 (0.38%)  0/258 (0.00%) 
CEREBRAL CYST * 1  1/263 (0.38%)  0/258 (0.00%) 
CEREBRAL HAEMORRHAGE * 1  1/263 (0.38%)  0/258 (0.00%) 
CEREBRAL VENTRICLE DILATATION * 1  0/263 (0.00%)  1/258 (0.39%) 
COMA * 1  0/263 (0.00%)  1/258 (0.39%) 
COORDINATION ABNORMAL * 1  1/263 (0.38%)  0/258 (0.00%) 
FACIAL NERVE DISORDER * 1  1/263 (0.38%)  0/258 (0.00%) 
HAEMORRHAGE INTRACRANIAL * 1  0/263 (0.00%)  1/258 (0.39%) 
HYDROCEPHALUS * 1  1/263 (0.38%)  0/258 (0.00%) 
LETHARGY * 1  1/263 (0.38%)  0/258 (0.00%) 
MEMORY IMPAIRMENT * 1  0/263 (0.00%)  1/258 (0.39%) 
MIGRAINE * 1  1/263 (0.38%)  0/258 (0.00%) 
NEUROLOGICAL DECOMPENSATION * 1  0/263 (0.00%)  1/258 (0.39%) 
NORMAL PRESSURE HYDROCEPHALUS * 1  1/263 (0.38%)  0/258 (0.00%) 
POST HERPETIC NEURALGIA * 1  0/263 (0.00%)  1/258 (0.39%) 
PYRAMIDAL TRACT SYNDROME * 1  1/263 (0.38%)  0/258 (0.00%) 
SYNCOPE * 1  1/263 (0.38%)  0/258 (0.00%) 
TRANSIENT ISCHAEMIC ATTACK * 1  0/263 (0.00%)  1/258 (0.39%) 
TRIGEMINAL NEURALGIA * 1  1/263 (0.38%)  0/258 (0.00%) 
VIITH NERVE PARALYSIS * 1  1/263 (0.38%)  0/258 (0.00%) 
VISUAL FIELD DEFECT * 1  1/263 (0.38%)  0/258 (0.00%) 
Psychiatric disorders     
CONFUSIONAL STATE * 1  5/263 (1.90%)  2/258 (0.78%) 
AGITATION * 1  0/263 (0.00%)  3/258 (1.16%) 
DEPRESSION * 1  1/263 (0.38%)  1/258 (0.39%) 
DELIRIUM * 1  0/263 (0.00%)  1/258 (0.39%) 
DISORIENTATION * 1  1/263 (0.38%)  0/258 (0.00%) 
DYSTHYMIC DISORDER * 1  1/263 (0.38%)  0/258 (0.00%) 
HALLUCINATION, VISUAL * 1  0/263 (0.00%)  1/258 (0.39%) 
MENTAL STATUS CHANGES * 1  1/263 (0.38%)  0/258 (0.00%) 
PANIC ATTACK * 1  0/263 (0.00%)  1/258 (0.39%) 
PERSONALITY CHANGE * 1  1/263 (0.38%)  0/258 (0.00%) 
PSYCHOTIC DISORDER * 1  0/263 (0.00%)  1/258 (0.39%) 
SCHIZOPHRENIA * 1  1/263 (0.38%)  0/258 (0.00%) 
Renal and urinary disorders     
RENAL FAILURE * 1  1/263 (0.38%)  1/258 (0.39%) 
BLADDER NECK OBSTRUCTION * 1  1/263 (0.38%)  0/258 (0.00%) 
CALCULUS URINARY * 1  0/263 (0.00%)  1/258 (0.39%) 
RENAL FAILURE ACUTE * 1  0/263 (0.00%)  1/258 (0.39%) 
Respiratory, thoracic and mediastinal disorders     
PULMONARY EMBOLISM * 1  12/263 (4.56%)  7/258 (2.71%) 
PNEUMONIA ASPIRATION * 1  4/263 (1.52%)  0/258 (0.00%) 
ACUTE RESPIRATORY DISTRESS SYNDROME * 1  0/263 (0.00%)  2/258 (0.78%) 
DYSPNOEA * 1  1/263 (0.38%)  1/258 (0.39%) 
RESPIRATORY FAILURE * 1  2/263 (0.76%)  0/258 (0.00%) 
CHRONIC OBSTRUCTIVE PULMONARY DISEASE * 1  1/263 (0.38%)  0/258 (0.00%) 
HAEMOTHORAX * 1  1/263 (0.38%)  0/258 (0.00%) 
HYPOXIA * 1  1/263 (0.38%)  0/258 (0.00%) 
PLEURAL EFFUSION * 1  0/263 (0.00%)  1/258 (0.39%) 
PNEUMONITIS * 1  1/263 (0.38%)  0/258 (0.00%) 
RESPIRATORY DISTRESS * 1  1/263 (0.38%)  0/258 (0.00%) 
VOCAL CORD POLYP * 1  1/263 (0.38%)  0/258 (0.00%) 
Skin and subcutaneous tissue disorders     
DRUG ERUPTION * 1  0/263 (0.00%)  1/258 (0.39%) 
EXFOLIATIVE RASH * 1  1/263 (0.38%)  0/258 (0.00%) 
RASH * 1  0/263 (0.00%)  1/258 (0.39%) 
Surgical and medical procedures     
BLADDER CATHETERISATION * 1  1/263 (0.38%)  0/258 (0.00%) 
PALLIATIVE CARE * 1  0/263 (0.00%)  1/258 (0.39%) 
SURGERY * 1  0/263 (0.00%)  1/258 (0.39%) 
Vascular disorders     
DEEP VEIN THROMBOSIS * 1  5/263 (1.90%)  6/258 (2.33%) 
HYPOTENSION * 1  3/263 (1.14%)  1/258 (0.39%) 
HYPERTENSION * 1  1/263 (0.38%)  2/258 (0.78%) 
PELVIC VENOUS THROMBOSIS * 1  1/263 (0.38%)  1/258 (0.39%) 
THROMBOSIS * 1  0/263 (0.00%)  1/258 (0.39%) 
EMBOLISM VENOUS * 1  1/263 (0.38%)  0/258 (0.00%) 
SUBCLAVIAN VEIN THROMBOSIS * 1  1/263 (0.38%)  0/258 (0.00%) 
VENOUS THROMBOSIS * 1  1/263 (0.38%)  0/258 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 15.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cilengitide + Temozolomide + Radiotherapy Temozolomide + Radiotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   251/263 (95.44%)   240/258 (93.02%) 
Blood and lymphatic system disorders     
THROMBOCYTOPENIA * 1  46/263 (17.49%)  46/258 (17.83%) 
LYMPHOPENIA * 1  45/263 (17.11%)  35/258 (13.57%) 
LEUKOPENIA * 1  29/263 (11.03%)  23/258 (8.91%) 
NEUTROPENIA * 1  29/263 (11.03%)  18/258 (6.98%) 
ANAEMIA * 1  15/263 (5.70%)  15/258 (5.81%) 
Eye disorders     
VISION BLURRED * 1  16/263 (6.08%)  11/258 (4.26%) 
Gastrointestinal disorders     
NAUSEA * 1  128/263 (48.67%)  125/258 (48.45%) 
CONSTIPATION * 1  100/263 (38.02%)  78/258 (30.23%) 
VOMITING * 1  77/263 (29.28%)  83/258 (32.17%) 
DIARRHOEA * 1  44/263 (16.73%)  20/258 (7.75%) 
DYSPEPSIA * 1  24/263 (9.13%)  8/258 (3.10%) 
ABDOMINAL PAIN UPPER * 1  15/263 (5.70%)  7/258 (2.71%) 
ABDOMINAL PAIN * 1  15/263 (5.70%)  6/258 (2.33%) 
General disorders     
FATIGUE * 1  98/263 (37.26%)  84/258 (32.56%) 
ASTHENIA * 1  42/263 (15.97%)  20/258 (7.75%) 
OEDEMA PERIPHERAL * 1  36/263 (13.69%)  24/258 (9.30%) 
PYREXIA * 1  26/263 (9.89%)  16/258 (6.20%) 
Infections and infestations     
UPPER RESPIRATORY TRACT INFECTION * 1  28/263 (10.65%)  16/258 (6.20%) 
NASOPHARYNGITIS * 1  32/263 (12.17%)  11/258 (4.26%) 
URINARY TRACT INFECTION * 1  16/263 (6.08%)  21/258 (8.14%) 
Injury, poisoning and procedural complications     
RADIATION SKIN INJURY * 1  20/263 (7.60%)  22/258 (8.53%) 
Investigations     
ALANINE AMINOTRANSFERASE INCREASED * 1  21/263 (7.98%)  17/258 (6.59%) 
WEIGHT DECREASED * 1  15/263 (5.70%)  14/258 (5.43%) 
Metabolism and nutrition disorders     
DECREASED APPETITE * 1  53/263 (20.15%)  45/258 (17.44%) 
HYPOKALAEMIA * 1  14/263 (5.32%)  8/258 (3.10%) 
Musculoskeletal and connective tissue disorders     
BACK PAIN * 1  31/263 (11.79%)  7/258 (2.71%) 
PAIN IN EXTREMITY * 1  24/263 (9.13%)  13/258 (5.04%) 
MUSCULAR WEAKNESS * 1  21/263 (7.98%)  14/258 (5.43%) 
ARTHRALGIA * 1  25/263 (9.51%)  6/258 (2.33%) 
Nervous system disorders     
HEADACHE * 1  114/263 (43.35%)  87/258 (33.72%) 
DIZZINESS * 1  33/263 (12.55%)  24/258 (9.30%) 
CONVULSION * 1  37/263 (14.07%)  14/258 (5.43%) 
MEMORY IMPAIRMENT * 1  27/263 (10.27%)  17/258 (6.59%) 
APHASIA * 1  24/263 (9.13%)  11/258 (4.26%) 
TREMOR * 1  20/263 (7.60%)  11/258 (4.26%) 
PARAESTHESIA * 1  14/263 (5.32%)  7/258 (2.71%) 
Psychiatric disorders     
INSOMNIA * 1  35/263 (13.31%)  24/258 (9.30%) 
DEPRESSION * 1  19/263 (7.22%)  14/258 (5.43%) 
ANXIETY * 1  13/263 (4.94%)  14/258 (5.43%) 
Renal and urinary disorders     
URINARY INCONTINENCE * 1  15/263 (5.70%)  4/258 (1.55%) 
Respiratory, thoracic and mediastinal disorders     
COUGH * 1  51/263 (19.39%)  23/258 (8.91%) 
DYSPNOEA * 1  21/263 (7.98%)  8/258 (3.10%) 
OROPHARYNGEAL PAIN * 1  20/263 (7.60%)  6/258 (2.33%) 
Skin and subcutaneous tissue disorders     
ALOPECIA * 1  70/263 (26.62%)  70/258 (27.13%) 
PRURITUS * 1  32/263 (12.17%)  15/258 (5.81%) 
RASH * 1  28/263 (10.65%)  18/258 (6.98%) 
ERYTHEMA * 1  21/263 (7.98%)  10/258 (3.88%) 
DRY SKIN * 1  16/263 (6.08%)  12/258 (4.65%) 
Vascular disorders     
HYPERTENSION * 1  17/263 (6.46%)  7/258 (2.71%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 15.0
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
All manuscripts and materials relating to Study shall be submitted to Sponsor at least 60 days prior to submitting/presenting and allow Sponsor 60 days for review. If Sponsor requests, any confidential information shall be removed. In multi-center study, any publication shall not be made before the first multi-center publication; provided, however, that if no multi-center publication is made within 1 year from database lock, then Site may publish individually in accordance with this provision.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Merck KGaA Communication Center
Organization: Merck Serono, a division of Merck KGaA
Phone: +49-6151-72-5200
EMail: service@merckgroup.com
Publications of Results:
Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial Roger Stupp, Monika E Hegi, Thierry Gorlia, Sara C Erridge, James Perry, Yong-Kil Hong, Kenneth D Aldape, Benoit Lhermitte, Torsten Pietsch, Danica Grujicic, Joachim Peter Steinbach, Wolfgang Wick, Rafał Tarnawski, Do-Hyun Nam, Peter Hau, Astrid Weyerbrock, Martin J B Taphoorn, Chiung-Chyi Shen, Nalini Rao, László Thurzo, Ulrich Herrlinger, Tejpal Gupta, Rolf-Dieter Kortmann, Krystyna Adamska, Catherine McBain, Alba A Brandes, Joerg Christian Tonn, Oliver Schnell, Thomas Wiegel, Chae-Yong Kim, Louis Burt Nabors, David A Reardon, Martin J van den Bent, Christine Hicking, Andriy Markivskyy, Martin Picard, Michael Weller The Lancet Oncology 20 August 2014(Article in Press DOI: 10.1016/S1470-2045(14)70379-1)
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Stupp R, Hegi ME, Gorlia T, Erridge SC, Perry J, Hong YK, Aldape KD, Lhermitte B, Pietsch T, Grujicic D, Steinbach JP, Wick W, Tarnawski R, Nam DH, Hau P, Weyerbrock A, Taphoorn MJ, Shen CC, Rao N, Thurzo L, Herrlinger U, Gupta T, Kortmann RD, Adamska K, McBain C, Brandes AA, Tonn JC, Schnell O, Wiegel T, Kim CY, Nabors LB, Reardon DA, van den Bent MJ, Hicking C, Markivskyy A, Picard M, Weller M; European Organisation for Research and Treatment of Cancer (EORTC); Canadian Brain Tumor Consortium; CENTRIC study team. Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Sep;15(10):1100-8. doi: 10.1016/S1470-2045(14)70379-1. Epub 2014 Aug 19.
Layout table for additonal information
Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT00689221    
Other Study ID Numbers: EMD 121974-011
EORTC 26071-22072
2007-004344-78 ( EudraCT Number )
First Submitted: May 29, 2008
First Posted: June 3, 2008
Results First Submitted: August 28, 2014
Results First Posted: November 4, 2014
Last Update Posted: November 4, 2014