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

• Sponsor: EMD Serono (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00689221
• Collaborator: European Organisation for Research and Treatment of Cancer - EORTC (Other), Merck KGaA, Darmstadt, Germany (Industry)
• Enrollment: 545
• Locations: 2
• Arms: 2
• Duration (Months): 59
• Patients Per Site: 272.5
• Patients Per Site Per Month: 4.6

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma	Drug: Cilengitide; Drug: Temozolomide; Radiation: Radiotherapy	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 545 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Cilengitide for Subjects With Newly Diagnosed Glioblastoma and Methylated MGMT Gene Promoter - A Multicenter, Open-label, Controlled Phase III Study, Testing Cilengitide in Combination With Standard Treatment (Temozolomide With Concomitant Radiation Therapy, Followed by Temozolomide Maintenance Therapy) Versus Standard Treatment Alone (CENTRIC)
• Study Start Date: Sep 1, 2008
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cilengitide + Temozolomide + Radiotherapy	Drug: Cilengitide; 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.; Drug: Temozolomide; 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.; Radiation: Radiotherapy; 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.
Active Comparator: Temozolomide + Radiotherapy	Drug: Temozolomide; 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.; Radiation: Radiotherapy; 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.

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) Time [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)]

   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.

Secondary Outcome Measures

1. Progression Free Survival (PFS) Time - Investigator and Independent Read [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)]

   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

2. Maximum Observed Plasma Concentration (Cmax) [Day 1 of Week -1]

   The Cmax for cilengitide was calculated by non-compartmental analysis using the computer program WinNonlin, Version 6.2.1.

3. Time to Maximum Plasma Concentration (Tmax) [Day 1 of Week -1]

   The Tmax for cilengitide was calculated by non-compartmental analysis using the computer program WinNonlin, Version 6.2.1.

4. Area Under the Plasma Concentration Curve From Time 0 to 6 Hours (AUC [0-6]) After Dose [Day 1 of Week -1]

   The AUC (0-6) for cilengitide was calculated by non-compartmental analysis using the computer program WinNonlin, Version 6.2.1.

5. European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores [Up to 50 months]

   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.

6. European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores [Up to 50 months]

   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.

7. EuroQol 5-Dimensions (EQ-5D) Questionnaire Index [Up to 50 months]

   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).

8. Number of Participants With Change From Baseline in Work Status at End of Study [Baseline, End of study (up to cut-off date, [19 Nov 2012])]

   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).

9. 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 [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)]

   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.

10. 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 [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)]

    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.

11. Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) and Lab Parameters [Up to 50 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. 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

2. Newly diagnosed histologically proven supratentorial glioblastoma (World Health Organization [WHO] Grade IV)

3. Proven methylated MGMT gene promoter methylation status

4. 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)

5. Stable or decreasing dose of steroids for greater than or equal to (>=) 5 days prior to randomization

6. Eastern Cooperative Oncology Group performance score (ECOG PS) of 0-1

7. 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:

1. 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)

1. Other protocol defined inclusion criteria could apply

Exclusion Criteria:

1. Prior chemotherapy within the last 5 years

2. Prior RTX of the head

3. Receiving concurrent investigational agents or has received an investigational agent within the past 30 days prior to the first dose of cilengitide

4. Prior systemic antiangiogenic therapy

5. Placement of Gliadel® wafer at surgery

6. Inability to undergo Gd-MRI.

7. Planned surgery for other diseases

8. History of recent peptic ulcer disease (endoscopically proven gastric ulcer, duodenal ulcer, or esophageal ulcer) within 6 months of enrollment

9. 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

10. History of coagulation disorder associated with bleeding or recurrent thrombotic events

11. Clinically manifest myocardial insufficiency (New York Heart Association [NYHA] III,

1. or history of myocardial infarction during the past 6 months; uncontrolled arterial hypertension

1. Other protocol defined exclusion criteria could apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Please Contact U.S. Medical Information Located in	Rockland	Massachusetts	United States
2	Please Contact the Merck KGaA Communication Center Located in	Darmstadt		Germany

Sponsors and Collaborators

• EMD Serono
• European Organisation for Research and Treatment of Cancer - EORTC
• Merck KGaA, Darmstadt, Germany

Investigators

• Study Chair: Roger Stupp, Prof. Dr., University of Lausanne Medical Center (CHUV)
• Study Director: Andriy Markivskyy, MD, Merck KGaA, Darmstadt, Germany

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: EMD Serono
• ClinicalTrials.gov Identifier: NCT00689221
• Other Study ID Numbers: EMD 121974-011; EORTC 26071-22072; 2007-004344-78
• First Posted: Jun 3, 2008
• Last Update Posted: Nov 4, 2014
• Last Verified: Oct 1, 2014

• Keywords provided by EMD Serono: newly diagnosed Glioblastoma (WHO Grade IV); Cilengitide; Temozolomide; Radiotherapy
• Additional relevant MeSH terms: Glioblastoma; Temozolomide

Study Results

Participant Flow

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 Detail	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
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

Baseline Characteristics

Arm/Group Title	Cilengitide + Temozolomide + Radiotherapy	Temozolomide + Radiotherapy	Total
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 Participants	272	273	545
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.8 (11.00)	56.0 (10.97)	56.4 (10.98)
Sex: Female, Male (Count of Participants)
Female	124 45.6%	130 47.6%	254 46.6%
Male	148 54.4%	143 52.4%	291 53.4%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS) Time
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)

Outcome Measure Data

Analysis Population Description

ITT population included all the participants who were randomized to study treatment.

Arm/Group Title	Cilengitide + Temozolomide + Radiotherapy	Temozolomide + Radiotherapy
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.
Measure Participants	272	273
Median (95% Confidence Interval) [Months]	26.3	26.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cilengitide + Temozolomide + Radiotherapy, Temozolomide + Radiotherapy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8623
	Comments	P-value is not adjusted for multiple testing.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.021
	Confidence Interval	(2-Sided) 95%; 0.808 to 1.291
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Progression Free Survival (PFS) Time - Investigator and Independent Read
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)

Outcome Measure Data

Analysis Population Description

ITT population included all the participants who were randomized to study treatment.

Arm/Group Title	Cilengitide + Temozolomide + Radiotherapy	Temozolomide + Radiotherapy
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.
Measure Participants	272	273
PFS Time: Investigator read	13.5	10.7
PFS Time: Independent read	10.6	7.9

3. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax)
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

Outcome Measure Data

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
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.
Measure Participants	38
Mean (Standard Deviation) [nanogram per milliliter (ng/mL)]	167363.2 (368301.11)

4. Secondary Outcome

Title	Time to Maximum Plasma Concentration (Tmax)
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

Outcome Measure Data

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
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.
Measure Participants	38
Mean (Standard Deviation) [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
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

Outcome Measure Data

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
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.
Measure Participants	37
Mean (Standard Deviation) [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
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

Outcome Measure Data

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
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.
Measure Participants	71	93
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
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

Outcome Measure Data

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
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.
Measure Participants	68	87
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
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

Outcome Measure Data

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
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.
Measure Participants	69	90
Mean (Standard Deviation) [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
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])

Outcome Measure Data

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
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.
Measure Participants	263	258
Baseline: FT, EOS: FT	3 1.1%	6 2.2%
Baseline: FT, EOS: PT1	2 0.7%	1 0.4%
Baseline: FT, EOS: PT2	1 0.4%	0 0%
Baseline: FT, EOS: PT3	0 0%	0 0%
Baseline: FT, EOS: U/R	24 8.8%	22 8.1%
Baseline: PT1, EOS: FT	3 1.1%	2 0.7%
Baseline: PT1, EOS: PT1	3 1.1%	1 0.4%
Baseline: PT1, EOS: PT2	0 0%	0 0%
Baseline: PT1, EOS: PT3	0 0%	0 0%
Baseline: PT1, EOS: U/R	9 3.3%	12 4.4%
Baseline: PT2, EOS: FT	0 0%	1 0.4%
Baseline: PT2, EOS: PT1	0 0%	0 0%
Baseline: PT2, EOS: PT2	0 0%	0 0%
Baseline: PT2, EOS: PT3	1 0.4%	0 0%
Baseline: PT2, EOS: U/R	5 1.8%	4 1.5%
Baseline: PT3, EOS: FT	0 0%	0 0%
Baseline: PT3, EOS: PT1	0 0%	0 0%
Baseline: PT3, EOS: PT2	0 0%	0 0%
Baseline: PT3, EOS: PT3	0 0%	0 0%
Baseline: PT3, EOS: U/R	0 0%	0 0%
Baseline: U/R, EOS: FT	5 1.8%	8 2.9%
Baseline: U/R, EOS: PT1	5 1.8%	7 2.6%
Baseline: U/R, EOS: PT2	1 0.4%	1 0.4%
Baseline: U/R, EOS: PT3	0 0%	0 0%
Baseline: U/R, EOS: U/R	199 73.2%	191 70%
Baseline: Missing, EOS: FT	0 0%	0 0%
Baseline: Missing, EOS: PT1	0 0%	0 0%
Baseline: Missing, EOS: PT2	0 0%	0 0%
Baseline: Missing, EOS: PT3	0 0%	0 0%
Baseline: Missing, EOS: U/R	1 0.4%	1 0.4%
Baseline: Missing, EOS: Missing	1 0.4%	1 0.4%

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
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)

Outcome Measure Data

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
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.
Measure Participants	263	258
AEs	261 96%	253 92.7%
Serious AEs	138 50.7%	115 42.1%
Treatment-related AEs	229 84.2%	222 81.3%
Treatment-Related Serious AEs	55 20.2%	47 17.2%
AEs leading to death	11 4%	9 3.3%
Treatment-related AEs leading to death	3 1.1%	3 1.1%
AEs with NCI-CTC toxicity Grade 3 or 4	169 62.1%	158 57.9%
Treatment-related AEs of Grade 3 or 4	100 36.8%	101 37%

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
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)

Outcome Measure Data

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
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.
Measure Participants	263	258
SMQ:Thromboembolic events	35 12.9%	23 8.4%
SMQ: Hemorrhage	4 1.5%	4 1.5%

12. Secondary Outcome

Title	Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) and Lab Parameters
Time Frame	Up to 50 months

Outcome Measure Data

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
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.
Measure Participants	0	0

Adverse Events

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)
Arm/Group Title	Cilengitide + Temozolomide + Radiotherapy		Temozolomide + Radiotherapy
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cilengitide + Temozolomide + Radiotherapy		Temozolomide + Radiotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	138/263 (52.5%)		115/258 (44.6%)
Blood and lymphatic system disorders
THROMBOCYTOPENIA	16/263 (6.1%)		24/258 (9.3%)
NEUTROPENIA	6/263 (2.3%)		11/258 (4.3%)
LEUKOPENIA	4/263 (1.5%)		10/258 (3.9%)
ANAEMIA	2/263 (0.8%)		2/258 (0.8%)
PANCYTOPENIA	1/263 (0.4%)		2/258 (0.8%)
LYMPHOPENIA	1/263 (0.4%)		1/258 (0.4%)
DISSEMINATED INTRAVASCULAR COAGULATION	0/263 (0%)		1/258 (0.4%)
FEBRILE BONE MARROW APLASIA	0/263 (0%)		1/258 (0.4%)
FEBRILE NEUTROPENIA	1/263 (0.4%)		0/258 (0%)
HAEMATOTOXICITY	0/263 (0%)		1/258 (0.4%)
Cardiac disorders
ATRIAL FIBRILLATION	1/263 (0.4%)		1/258 (0.4%)
ACUTE MYOCARDIAL INFARCTION	0/263 (0%)		1/258 (0.4%)
CARDIAC FAILURE	0/263 (0%)		1/258 (0.4%)
CORONARY ARTERY THROMBOSIS	0/263 (0%)		1/258 (0.4%)
MYOCARDIAL ISCHAEMIA	1/263 (0.4%)		0/258 (0%)
Ear and labyrinth disorders
VERTIGO	1/263 (0.4%)		1/258 (0.4%)
Endocrine disorders
ADRENAL INSUFFICIENCY	0/263 (0%)		1/258 (0.4%)
INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION	0/263 (0%)		1/258 (0.4%)
Gastrointestinal disorders
VOMITING	3/263 (1.1%)		4/258 (1.6%)
NAUSEA	2/263 (0.8%)		2/258 (0.8%)
ABDOMINAL PAIN	1/263 (0.4%)		2/258 (0.8%)
CONSTIPATION	2/263 (0.8%)		0/258 (0%)
DYSPHAGIA	1/263 (0.4%)		1/258 (0.4%)
ENTERITIS	2/263 (0.8%)		0/258 (0%)
UPPER GASTROINTESTINAL HAEMORRHAGE	1/263 (0.4%)		1/258 (0.4%)
ABDOMINAL PAIN UPPER	0/263 (0%)		1/258 (0.4%)
COLITIS	0/263 (0%)		1/258 (0.4%)
DIARRHOEA	1/263 (0.4%)		0/258 (0%)
GASTRIC DISORDER	1/263 (0.4%)		0/258 (0%)
General disorders
PYREXIA	4/263 (1.5%)		3/258 (1.2%)
ASTHENIA	5/263 (1.9%)		1/258 (0.4%)
FATIGUE	4/263 (1.5%)		1/258 (0.4%)
GENERAL PHYSICAL HEALTH DETERIORATION	2/263 (0.8%)		3/258 (1.2%)
DISEASE PROGRESSION	4/263 (1.5%)		0/258 (0%)
DEVICE MALFUNCTION	1/263 (0.4%)		0/258 (0%)
CHEST PAIN	1/263 (0.4%)		0/258 (0%)
GAIT DISTURBANCE	1/263 (0.4%)		0/258 (0%)
PAIN	0/263 (0%)		1/258 (0.4%)
Hepatobiliary disorders
HEPATIC FAILURE	0/263 (0%)		2/258 (0.8%)
CHOLECYSTITIS	0/263 (0%)		1/258 (0.4%)
DRUG-INDUCED LIVER INJURY	1/263 (0.4%)		0/258 (0%)
HEPATIC STEATOSIS	1/263 (0.4%)		0/258 (0%)
Immune system disorders
DRUG HYPERSENSITIVITY	1/263 (0.4%)		0/258 (0%)
HYPERSENSITIVITY	1/263 (0.4%)		0/258 (0%)
Infections and infestations
PNEUMONIA	9/263 (3.4%)		7/258 (2.7%)
URINARY TRACT INFECTION	2/263 (0.8%)		4/258 (1.6%)
LOWER RESPIRATORY TRACT INFECTION	3/263 (1.1%)		0/258 (0%)
CELLULITIS	1/263 (0.4%)		1/258 (0.4%)
GASTROENTERITIS	1/263 (0.4%)		1/258 (0.4%)
H1N1 INFLUENZA	1/263 (0.4%)		1/258 (0.4%)
POSTOPERATIVE WOUND INFECTION	1/263 (0.4%)		1/258 (0.4%)
SEPSIS	2/263 (0.8%)		0/258 (0%)
SEPTIC SHOCK	0/263 (0%)		2/258 (0.8%)
WOUND INFECTION	2/263 (0.8%)		0/258 (0%)
NECROTISING FASCIITIS	0/263 (0%)		1/258 (0.4%)
WOUND ABSCESS	1/263 (0.4%)		0/258 (0%)
APPENDICITIS	1/263 (0.4%)		0/258 (0%)
BACTERIAL INFECTION	1/263 (0.4%)		0/258 (0%)
BRAIN ABSCESS	0/263 (0%)		1/258 (0.4%)
BRONCHITIS	1/263 (0.4%)		0/258 (0%)
BRONCHOPNEUMONIA	1/263 (0.4%)		0/258 (0%)
DEVICE RELATED SEPSIS	1/263 (0.4%)		0/258 (0%)
EPIGLOTTITIS	1/263 (0.4%)		0/258 (0%)
ESCHERICHIA URINARY TRACT INFECTION	1/263 (0.4%)		0/258 (0%)
HERPES ZOSTER	1/263 (0.4%)		0/258 (0%)
INFLUENZA	0/263 (0%)		1/258 (0.4%)
MENINGITIS	0/263 (0%)		1/258 (0.4%)
ORAL CANDIDIASIS	1/263 (0.4%)		0/258 (0%)
OSTEOMYELITIS	1/263 (0.4%)		0/258 (0%)
PYELONEPHRITIS ACUTE	0/263 (0%)		1/258 (0.4%)
SKIN INFECTION	1/263 (0.4%)		0/258 (0%)
SUBCUTANEOUS ABSCESS	0/263 (0%)		1/258 (0.4%)
Injury, poisoning and procedural complications
FALL	1/263 (0.4%)		2/258 (0.8%)
FACIAL BONES FRACTURE	0/263 (0%)		1/258 (0.4%)
FRACTURE	1/263 (0.4%)		0/258 (0%)
LIMB INJURY	0/263 (0%)		1/258 (0.4%)
OPEN WOUND	1/263 (0.4%)		0/258 (0%)
OVERDOSE	0/263 (0%)		1/258 (0.4%)
POST PROCEDURAL OEDEMA	0/263 (0%)		1/258 (0.4%)
POSTOPERATIVE WOUND COMPLICATION	1/263 (0.4%)		0/258 (0%)
RADIATION INJURY	0/263 (0%)		1/258 (0.4%)
RADIATION NECROSIS	1/263 (0.4%)		0/258 (0%)
RADIUS FRACTURE	1/263 (0.4%)		0/258 (0%)
THORACIC VERTEBRAL FRACTURE	0/263 (0%)		1/258 (0.4%)
Investigations
LYMPHOCYTE COUNT DECREASED	2/263 (0.8%)		1/258 (0.4%)
PLATELET COUNT DECREASED	2/263 (0.8%)		1/258 (0.4%)
BLOOD URIC ACID INCREASED	1/263 (0.4%)		0/258 (0%)
ELECTROCARDIOGRAM QT PROLONGED	1/263 (0.4%)		0/258 (0%)
FIBRIN D DIMER INCREASED	1/263 (0.4%)		0/258 (0%)
NEUTROPHIL COUNT DECREASED	1/263 (0.4%)		0/258 (0%)
TRANSAMINASES INCREASED	1/263 (0.4%)		0/258 (0%)
Metabolism and nutrition disorders
DEHYDRATION	1/263 (0.4%)		2/258 (0.8%)
HYPONATRAEMIA	1/263 (0.4%)		1/258 (0.4%)
DECREASED APPETITE	1/263 (0.4%)		0/258 (0%)
TYPE 2 DIABETES MELLITUS	1/263 (0.4%)		0/258 (0%)
HYPERGLYCAEMIA	0/263 (0%)		1/258 (0.4%)
HYPERURICAEMIA	1/263 (0.4%)		0/258 (0%)
HYPOCALCAEMIA	1/263 (0.4%)		0/258 (0%)
HYPOGLYCAEMIA	1/263 (0.4%)		0/258 (0%)
Musculoskeletal and connective tissue disorders
MUSCULAR WEAKNESS	1/263 (0.4%)		2/258 (0.8%)
BACK PAIN	0/263 (0%)		1/258 (0.4%)
MUSCLE SPASMS	1/263 (0.4%)		0/258 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA	1/263 (0.4%)		0/258 (0%)
GLIOBLASTOMA	0/263 (0%)		1/258 (0.4%)
INTRACRANIAL TUMOUR HAEMORRHAGE	1/263 (0.4%)		0/258 (0%)
METASTASES TO MENINGES	0/263 (0%)		1/258 (0.4%)
NEOPLASM RECURRENCE	1/263 (0.4%)		0/258 (0%)
NEURILEMMOMA	1/263 (0.4%)		0/258 (0%)
PANCREATIC CARCINOMA	1/263 (0.4%)		0/258 (0%)
SMALL CELL LUNG CANCER STAGE UNSPECIFIED	0/263 (0%)		1/258 (0.4%)
THYROID CANCER	1/263 (0.4%)		0/258 (0%)
TUMOUR HAEMORRHAGE	1/263 (0.4%)		0/258 (0%)
Nervous system disorders
CONVULSION	20/263 (7.6%)		14/258 (5.4%)
HEMIPARESIS	12/263 (4.6%)		1/258 (0.4%)
BRAIN OEDEMA	5/263 (1.9%)		5/258 (1.9%)
EPILEPSY	6/263 (2.3%)		3/258 (1.2%)
GRAND MAL CONVULSION	5/263 (1.9%)		3/258 (1.2%)
HEADACHE	5/263 (1.9%)		1/258 (0.4%)
PARTIAL SEIZURES	4/263 (1.5%)		2/258 (0.8%)
STATUS EPILEPTICUS	4/263 (1.5%)		1/258 (0.4%)
COGNITIVE DISORDER	3/263 (1.1%)		1/258 (0.4%)
DIZZINESS	3/263 (1.1%)		1/258 (0.4%)
SOMNOLENCE	3/263 (1.1%)		1/258 (0.4%)
ATAXIA	2/263 (0.8%)		1/258 (0.4%)
CEREBROVASCULAR ACCIDENT	2/263 (0.8%)		0/258 (0%)
INTRACRANIAL PRESSURE INCREASED	2/263 (0.8%)		0/258 (0%)
PERIPHERAL MOTOR NEUROPATHY	2/263 (0.8%)		0/258 (0%)
APHASIA	1/263 (0.4%)		1/258 (0.4%)
CEREBRAL ISCHAEMIA	1/263 (0.4%)		1/258 (0.4%)
SPEECH DISORDER	2/263 (0.8%)		0/258 (0%)
DEPRESSED LEVEL OF CONSCIOUSNESS	1/263 (0.4%)		0/258 (0%)
PERIPHERAL SENSORY NEUROPATHY	1/263 (0.4%)		0/258 (0%)
BRAIN INJURY	1/263 (0.4%)		0/258 (0%)
CENTRAL NERVOUS SYSTEM NECROSIS	1/263 (0.4%)		0/258 (0%)
CEREBRAL CYST	1/263 (0.4%)		0/258 (0%)
CEREBRAL HAEMORRHAGE	1/263 (0.4%)		0/258 (0%)
CEREBRAL VENTRICLE DILATATION	0/263 (0%)		1/258 (0.4%)
COMA	0/263 (0%)		1/258 (0.4%)
COORDINATION ABNORMAL	1/263 (0.4%)		0/258 (0%)
FACIAL NERVE DISORDER	1/263 (0.4%)		0/258 (0%)
HAEMORRHAGE INTRACRANIAL	0/263 (0%)		1/258 (0.4%)
HYDROCEPHALUS	1/263 (0.4%)		0/258 (0%)
LETHARGY	1/263 (0.4%)		0/258 (0%)
MEMORY IMPAIRMENT	0/263 (0%)		1/258 (0.4%)
MIGRAINE	1/263 (0.4%)		0/258 (0%)
NEUROLOGICAL DECOMPENSATION	0/263 (0%)		1/258 (0.4%)
NORMAL PRESSURE HYDROCEPHALUS	1/263 (0.4%)		0/258 (0%)
POST HERPETIC NEURALGIA	0/263 (0%)		1/258 (0.4%)
PYRAMIDAL TRACT SYNDROME	1/263 (0.4%)		0/258 (0%)
SYNCOPE	1/263 (0.4%)		0/258 (0%)
TRANSIENT ISCHAEMIC ATTACK	0/263 (0%)		1/258 (0.4%)
TRIGEMINAL NEURALGIA	1/263 (0.4%)		0/258 (0%)
VIITH NERVE PARALYSIS	1/263 (0.4%)		0/258 (0%)
VISUAL FIELD DEFECT	1/263 (0.4%)		0/258 (0%)
Psychiatric disorders
CONFUSIONAL STATE	5/263 (1.9%)		2/258 (0.8%)
AGITATION	0/263 (0%)		3/258 (1.2%)
DEPRESSION	1/263 (0.4%)		1/258 (0.4%)
DELIRIUM	0/263 (0%)		1/258 (0.4%)
DISORIENTATION	1/263 (0.4%)		0/258 (0%)
DYSTHYMIC DISORDER	1/263 (0.4%)		0/258 (0%)
HALLUCINATION, VISUAL	0/263 (0%)		1/258 (0.4%)
MENTAL STATUS CHANGES	1/263 (0.4%)		0/258 (0%)
PANIC ATTACK	0/263 (0%)		1/258 (0.4%)
PERSONALITY CHANGE	1/263 (0.4%)		0/258 (0%)
PSYCHOTIC DISORDER	0/263 (0%)		1/258 (0.4%)
SCHIZOPHRENIA	1/263 (0.4%)		0/258 (0%)
Renal and urinary disorders
RENAL FAILURE	1/263 (0.4%)		1/258 (0.4%)
BLADDER NECK OBSTRUCTION	1/263 (0.4%)		0/258 (0%)
CALCULUS URINARY	0/263 (0%)		1/258 (0.4%)
RENAL FAILURE ACUTE	0/263 (0%)		1/258 (0.4%)
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM	12/263 (4.6%)		7/258 (2.7%)
PNEUMONIA ASPIRATION	4/263 (1.5%)		0/258 (0%)
ACUTE RESPIRATORY DISTRESS SYNDROME	0/263 (0%)		2/258 (0.8%)
DYSPNOEA	1/263 (0.4%)		1/258 (0.4%)
RESPIRATORY FAILURE	2/263 (0.8%)		0/258 (0%)
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	1/263 (0.4%)		0/258 (0%)
HAEMOTHORAX	1/263 (0.4%)		0/258 (0%)
HYPOXIA	1/263 (0.4%)		0/258 (0%)
PLEURAL EFFUSION	0/263 (0%)		1/258 (0.4%)
PNEUMONITIS	1/263 (0.4%)		0/258 (0%)
RESPIRATORY DISTRESS	1/263 (0.4%)		0/258 (0%)
VOCAL CORD POLYP	1/263 (0.4%)		0/258 (0%)
Skin and subcutaneous tissue disorders
DRUG ERUPTION	0/263 (0%)		1/258 (0.4%)
EXFOLIATIVE RASH	1/263 (0.4%)		0/258 (0%)
RASH	0/263 (0%)		1/258 (0.4%)
Surgical and medical procedures
BLADDER CATHETERISATION	1/263 (0.4%)		0/258 (0%)
PALLIATIVE CARE	0/263 (0%)		1/258 (0.4%)
SURGERY	0/263 (0%)		1/258 (0.4%)
Vascular disorders
DEEP VEIN THROMBOSIS	5/263 (1.9%)		6/258 (2.3%)
HYPOTENSION	3/263 (1.1%)		1/258 (0.4%)
HYPERTENSION	1/263 (0.4%)		2/258 (0.8%)
PELVIC VENOUS THROMBOSIS	1/263 (0.4%)		1/258 (0.4%)
THROMBOSIS	0/263 (0%)		1/258 (0.4%)
EMBOLISM VENOUS	1/263 (0.4%)		0/258 (0%)
SUBCLAVIAN VEIN THROMBOSIS	1/263 (0.4%)		0/258 (0%)
VENOUS THROMBOSIS	1/263 (0.4%)		0/258 (0%)
Other (Not Including Serious) Adverse Events
	Cilengitide + Temozolomide + Radiotherapy		Temozolomide + Radiotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	251/263 (95.4%)		240/258 (93%)
Blood and lymphatic system disorders
THROMBOCYTOPENIA	46/263 (17.5%)		46/258 (17.8%)
LYMPHOPENIA	45/263 (17.1%)		35/258 (13.6%)
LEUKOPENIA	29/263 (11%)		23/258 (8.9%)
NEUTROPENIA	29/263 (11%)		18/258 (7%)
ANAEMIA	15/263 (5.7%)		15/258 (5.8%)
Eye disorders
VISION BLURRED	16/263 (6.1%)		11/258 (4.3%)
Gastrointestinal disorders
NAUSEA	128/263 (48.7%)		125/258 (48.4%)
CONSTIPATION	100/263 (38%)		78/258 (30.2%)
VOMITING	77/263 (29.3%)		83/258 (32.2%)
DIARRHOEA	44/263 (16.7%)		20/258 (7.8%)
DYSPEPSIA	24/263 (9.1%)		8/258 (3.1%)
ABDOMINAL PAIN UPPER	15/263 (5.7%)		7/258 (2.7%)
ABDOMINAL PAIN	15/263 (5.7%)		6/258 (2.3%)
General disorders
FATIGUE	98/263 (37.3%)		84/258 (32.6%)
ASTHENIA	42/263 (16%)		20/258 (7.8%)
OEDEMA PERIPHERAL	36/263 (13.7%)		24/258 (9.3%)
PYREXIA	26/263 (9.9%)		16/258 (6.2%)
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION	28/263 (10.6%)		16/258 (6.2%)
NASOPHARYNGITIS	32/263 (12.2%)		11/258 (4.3%)
URINARY TRACT INFECTION	16/263 (6.1%)		21/258 (8.1%)
Injury, poisoning and procedural complications
RADIATION SKIN INJURY	20/263 (7.6%)		22/258 (8.5%)
Investigations
ALANINE AMINOTRANSFERASE INCREASED	21/263 (8%)		17/258 (6.6%)
WEIGHT DECREASED	15/263 (5.7%)		14/258 (5.4%)
Metabolism and nutrition disorders
DECREASED APPETITE	53/263 (20.2%)		45/258 (17.4%)
HYPOKALAEMIA	14/263 (5.3%)		8/258 (3.1%)
Musculoskeletal and connective tissue disorders
BACK PAIN	31/263 (11.8%)		7/258 (2.7%)
PAIN IN EXTREMITY	24/263 (9.1%)		13/258 (5%)
MUSCULAR WEAKNESS	21/263 (8%)		14/258 (5.4%)
ARTHRALGIA	25/263 (9.5%)		6/258 (2.3%)
Nervous system disorders
HEADACHE	114/263 (43.3%)		87/258 (33.7%)
DIZZINESS	33/263 (12.5%)		24/258 (9.3%)
CONVULSION	37/263 (14.1%)		14/258 (5.4%)
MEMORY IMPAIRMENT	27/263 (10.3%)		17/258 (6.6%)
APHASIA	24/263 (9.1%)		11/258 (4.3%)
TREMOR	20/263 (7.6%)		11/258 (4.3%)
PARAESTHESIA	14/263 (5.3%)		7/258 (2.7%)
Psychiatric disorders
INSOMNIA	35/263 (13.3%)		24/258 (9.3%)
DEPRESSION	19/263 (7.2%)		14/258 (5.4%)
ANXIETY	13/263 (4.9%)		14/258 (5.4%)
Renal and urinary disorders
URINARY INCONTINENCE	15/263 (5.7%)		4/258 (1.6%)
Respiratory, thoracic and mediastinal disorders
COUGH	51/263 (19.4%)		23/258 (8.9%)
DYSPNOEA	21/263 (8%)		8/258 (3.1%)
OROPHARYNGEAL PAIN	20/263 (7.6%)		6/258 (2.3%)
Skin and subcutaneous tissue disorders
ALOPECIA	70/263 (26.6%)		70/258 (27.1%)
PRURITUS	32/263 (12.2%)		15/258 (5.8%)
RASH	28/263 (10.6%)		18/258 (7%)
ERYTHEMA	21/263 (8%)		10/258 (3.9%)
DRY SKIN	16/263 (6.1%)		12/258 (4.7%)
Vascular disorders
HYPERTENSION	17/263 (6.5%)		7/258 (2.7%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.