Glioblastoma
Conditions
Keywords
newly diagnosed Glioblastoma (WHO Grade IV), Cilengitide, Temozolomide, Radiotherapy
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.
Interventions
DRUGCilengitide
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.
DRUGTemozolomide
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.
RADIATIONRadiotherapy
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.
Sponsors
European Organisation for Research and Treatment of Cancer - EORTC
Merck KGaA, Darmstadt, Germany
EMD Serono
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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: a) Age \< 50 years and ECOG PS 1 or b) Age \>= 50 years, underwent prior partial or total tumor resection, mini mental state examination \[MMSE\] \>= 27). Class V (meeting one of the following criteria: a) Age \>= 50 years and underwent prior partial or total tumor resection, MMSE \< 27 or b) Age \>= 50 years and underwent prior tumor biopsy only) 8. 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, IV) or history of myocardial infarction during the past 6 months; uncontrolled arterial hypertension 12. Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 |
| 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). |
| 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. |
| 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. |
| Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) and Lab Parameters | Up to 50 months | — |
| 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). |
Countries
Germany, United States
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 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.
Participants by arm
| Arm | Count |
|---|---|
| Cilengitide + Temozolomide + Radiotherapy 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. | 272 |
| Temozolomide + Radiotherapy 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. | 273 |
| Total | 545 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Ongoing at cut-off date | 39 | 36 |
Baseline characteristics
| Characteristic | Cilengitide + Temozolomide + Radiotherapy | Temozolomide + Radiotherapy | Total |
|---|---|---|---|
| Age, Continuous | 56.8 years STANDARD_DEVIATION 11 | 56.0 years STANDARD_DEVIATION 10.97 | 56.4 years STANDARD_DEVIATION 10.98 |
| Sex: Female, Male Female | 124 Participants | 130 Participants | 254 Participants |
| Sex: Female, Male Male | 148 Participants | 143 Participants | 291 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 251 / 263 | 240 / 258 |
| serious Total, serious adverse events | 138 / 263 | 115 / 258 |
Outcome results
Primary
Overall Survival (OS) Time
The OS time is defined as the time (in months) from randomization to death or last day known to be alive. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier.
Time frame: Time from randomization to death or last day known to be alive, reported between day of first participant randomized, that is, Sep 2008 until cut-off date, (19 Nov 2012)
Population: ITT population included all the participants who were randomized to study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cilengitide + Temozolomide + Radiotherapy | Overall Survival (OS) Time | 26.3 Months |
| Temozolomide + Radiotherapy | Overall Survival (OS) Time | 26.3 Months |
p-value: 0.862395% CI: [0.808, 1.291]Log Rank
Secondary
Area Under the Plasma Concentration Curve From Time 0 to 6 Hours (AUC [0-6]) After Dose
The AUC (0-6) for cilengitide was calculated by non-compartmental analysis using the computer program WinNonlin, Version 6.2.1.
Time frame: Day 1 of Week -1
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cilengitide + Temozolomide + Radiotherapy | Area Under the Plasma Concentration Curve From Time 0 to 6 Hours (AUC [0-6]) After Dose | 295171.2 hour*ng/mL | Standard Deviation 198050.62 |
Secondary
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores
The QLQ-BN20 is a questionnaire specifically designed as the QLQ-C30 supplement for the evaluation of quality of life in brain tumor participants. It includes 4 multi-item sub-scales: future uncertainty, visual disorder, motor dysfunction, communication deficits, and 7 single-item scales: headaches, seizures, drowsiness, itchy skin, hair loss, weakness of legs, and bladder control. All items are rated on a 4-point Likert-type scale ('1=not at all', '2=a little', '3=quite a bit' and '4=very much'), and are linearly transformed to a 0-100 scale, with higher scores indicating more severe symptoms.
Time frame: Up to 50 months
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores | Communication Deficit (n=68, 86) | 26.14 units on a scale | Standard Deviation 28.59 |
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores | Drowsiness (n=66, 87) | 38.38 units on a scale | Standard Deviation 33.71 |
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores | Motor Dysfunction (n=68, 86) | 27.45 units on a scale | Standard Deviation 30.62 |
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores | Itchy Skin (n=68, 86) | 9.80 units on a scale | Standard Deviation 20 |
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores | Headaches (n=68, 86) | 25.98 units on a scale | Standard Deviation 32.5 |
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores | Hair Loss (n=66, 86) | 13.13 units on a scale | Standard Deviation 22.55 |
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores | Visual Disorder (n=68, 85) | 12.99 units on a scale | Standard Deviation 20.24 |
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores | Weakness of Legs (n=67, 85) | 24.38 units on a scale | Standard Deviation 34.12 |
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores | Seizures (n=68, 87) | 9.31 units on a scale | Standard Deviation 22.93 |
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores | Bladder Control (n=67, 85) | 19.40 units on a scale | Standard Deviation 29.67 |
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores | Future Uncertainty (n=68, 86) | 44.49 units on a scale | Standard Deviation 29.7 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores | Bladder Control (n=67, 85) | 10.20 units on a scale | Standard Deviation 21.22 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores | Future Uncertainty (n=68, 86) | 39.31 units on a scale | Standard Deviation 30.24 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores | Visual Disorder (n=68, 85) | 17.78 units on a scale | Standard Deviation 23.77 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores | Motor Dysfunction (n=68, 86) | 23.39 units on a scale | Standard Deviation 25.95 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores | Communication Deficit (n=68, 86) | 19.96 units on a scale | Standard Deviation 27.89 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores | Headaches (n=68, 86) | 21.71 units on a scale | Standard Deviation 26.45 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores | Seizures (n=68, 87) | 8.05 units on a scale | Standard Deviation 20.94 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores | Drowsiness (n=66, 87) | 35.25 units on a scale | Standard Deviation 31.07 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores | Itchy Skin (n=68, 86) | 13.57 units on a scale | Standard Deviation 24.72 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores | Hair Loss (n=66, 86) | 15.12 units on a scale | Standard Deviation 26.4 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Brain Module (EORTC QLQ-BN20) Sub-scale Scores | Weakness of Legs (n=67, 85) | 20.39 units on a scale | Standard Deviation 28.68 |
Secondary
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores
The EORTC QLQ-C30 is a questionnaire including following sub-scales: global health status, functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social activity), symptom scales (fatigue, nausea and vomiting, and pain) and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhoea and financial difficulties). Scores are averaged for each scale and transformed to 0-100 scale; higher score indicates better quality of life on global health status and functional scales and worse quality of life on symptom scales and financial difficulty scale.
Time frame: Up to 50 months
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Cognitive Functioning (n=70, 93) | 64.05 units on a scale | Standard Deviation 29.16 |
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Pain (n=71, 93) | 22.30 units on a scale | Standard Deviation 29.4 |
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Physical Functioning (n=71, 92) | 65.70 units on a scale | Standard Deviation 33.01 |
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Dyspnoea (n=71, 92) | 15.96 units on a scale | Standard Deviation 28.09 |
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Social Activity (n=71, 93) | 56.34 units on a scale | Standard Deviation 36.77 |
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Insomnia (n=71, 91) | 20.66 units on a scale | Standard Deviation 30.01 |
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Emotional Functioning (n=71, 93) | 67.49 units on a scale | Standard Deviation 30.58 |
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Appetite Loss (n=71, 92) | 21.13 units on a scale | Standard Deviation 30.47 |
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Fatigue (n=71, 92) | 44.37 units on a scale | Standard Deviation 33.07 |
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Constipation (n=71, 93) | 18.78 units on a scale | Standard Deviation 28.02 |
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Role Functioning (n=71, 92) | 56.34 units on a scale | Standard Deviation 37.31 |
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Diarrhoea (n=70, 92) | 6.67 units on a scale | Standard Deviation 18.48 |
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Nausea and Vomiting (n=71, 93) | 10.33 units on a scale | Standard Deviation 20.77 |
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Financial Difficulties (n=71, 93) | 27.23 units on a scale | Standard Deviation 31.53 |
| Cilengitide + Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Global Health Status (n=71, 92) | 54.34 units on a scale | Standard Deviation 25.58 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Financial Difficulties (n=71, 93) | 22.94 units on a scale | Standard Deviation 31.46 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Global Health Status (n=71, 92) | 55.43 units on a scale | Standard Deviation 27.02 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Physical Functioning (n=71, 92) | 67.46 units on a scale | Standard Deviation 31.19 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Role Functioning (n=71, 92) | 56.34 units on a scale | Standard Deviation 35.19 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Emotional Functioning (n=71, 93) | 67.00 units on a scale | Standard Deviation 27.29 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Cognitive Functioning (n=70, 93) | 65.41 units on a scale | Standard Deviation 31.4 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Social Activity (n=71, 93) | 62.72 units on a scale | Standard Deviation 35.73 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Fatigue (n=71, 92) | 39.73 units on a scale | Standard Deviation 29.93 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Nausea and Vomiting (n=71, 93) | 7.71 units on a scale | Standard Deviation 16.03 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Pain (n=71, 93) | 24.37 units on a scale | Standard Deviation 28.93 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Dyspnoea (n=71, 92) | 13.04 units on a scale | Standard Deviation 22.62 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Insomnia (n=71, 91) | 20.51 units on a scale | Standard Deviation 26.65 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Appetite Loss (n=71, 92) | 15.94 units on a scale | Standard Deviation 28.59 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Constipation (n=71, 93) | 13.98 units on a scale | Standard Deviation 25.69 |
| Temozolomide + Radiotherapy | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores | Diarrhoea (n=70, 92) | 4.35 units on a scale | Standard Deviation 13.28 |
Secondary
EuroQol 5-Dimensions (EQ-5D) Questionnaire Index
The EuroQuol-5D (EQ-5D) questionnaire is a measure of health status that provides a simple descriptive profile and a single index value. The optional part of the questionnaire was not applied. The EQ-5D defines health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5 items are combined to generate health profiles. These profiles were converted to a continuous single index score using a one to one matching. The lowest possible score is -0.594 (death) and the highest is 1.00 (full health).
Time frame: Up to 50 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cilengitide + Temozolomide + Radiotherapy | EuroQol 5-Dimensions (EQ-5D) Questionnaire Index | 0.598 units on a scale | Standard Deviation 0.43 |
| Temozolomide + Radiotherapy | EuroQol 5-Dimensions (EQ-5D) Questionnaire Index | 0.623 units on a scale | Standard Deviation 0.36 |
Secondary
Maximum Observed Plasma Concentration (Cmax)
The Cmax for cilengitide was calculated by non-compartmental analysis using the computer program WinNonlin, Version 6.2.1.
Time frame: Day 1 of Week -1
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cilengitide + Temozolomide + Radiotherapy | Maximum Observed Plasma Concentration (Cmax) | 167363.2 nanogram per milliliter (ng/mL) | Standard Deviation 368301.11 |
Secondary
Number of Participants With Adverse Events (AEs), Serious AEs, Treatment-Related AEs, Treatment-Related Serious AEs, AEs Leading to Death, Treatment Related AEs Leading to Death, AEs of Grade 3 or 4 and Treatment Related AEs of Grade 3 or 4
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)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cilengitide + Temozolomide + Radiotherapy | 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 | AEs | 261 Participants |
| Cilengitide + Temozolomide + Radiotherapy | 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 | Serious AEs | 138 Participants |
| Cilengitide + Temozolomide + Radiotherapy | 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 | Treatment-related AEs | 229 Participants |
| Cilengitide + Temozolomide + Radiotherapy | 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 | Treatment-Related Serious AEs | 55 Participants |
| Cilengitide + Temozolomide + Radiotherapy | 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 | AEs leading to death | 11 Participants |
| Cilengitide + Temozolomide + Radiotherapy | 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 | Treatment-related AEs leading to death | 3 Participants |
| Cilengitide + Temozolomide + Radiotherapy | 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 | AEs with NCI-CTC toxicity Grade 3 or 4 | 169 Participants |
| Cilengitide + Temozolomide + Radiotherapy | 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 | Treatment-related AEs of Grade 3 or 4 | 100 Participants |
| Temozolomide + Radiotherapy | 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 | Treatment-related AEs of Grade 3 or 4 | 101 Participants |
| Temozolomide + Radiotherapy | 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 | AEs | 253 Participants |
| Temozolomide + Radiotherapy | 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 | AEs leading to death | 9 Participants |
| Temozolomide + Radiotherapy | 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 | Serious AEs | 115 Participants |
| Temozolomide + Radiotherapy | 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 | AEs with NCI-CTC toxicity Grade 3 or 4 | 158 Participants |
| Temozolomide + Radiotherapy | 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 | Treatment-related AEs | 222 Participants |
| Temozolomide + Radiotherapy | 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 | Treatment-related AEs leading to death | 3 Participants |
| Temozolomide + Radiotherapy | 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 | Treatment-Related Serious AEs | 47 Participants |
Secondary
Number of Participants With AEs Belonging to Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) Thromboembolic Events and Hemorrhage With NCI-CTC Toxicity Grade 3 or 4
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)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cilengitide + Temozolomide + Radiotherapy | 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 | SMQ:Thromboembolic events | 35 Participants |
| Cilengitide + Temozolomide + Radiotherapy | 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 | SMQ: Hemorrhage | 4 Participants |
| Temozolomide + Radiotherapy | 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 | SMQ:Thromboembolic events | 23 Participants |
| Temozolomide + Radiotherapy | 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 | SMQ: Hemorrhage | 4 Participants |
Secondary
Number of Participants With Change From Baseline in Work Status at End of Study
Number of participants with change from baseline in work status (working full time \[FT\], part-time \[PT\], unemployed/retired \[U/R\]) at end of study (EOS) (up to cut-off date, \[19 Nov 2012\]) was reported. For the category 'part-time', the following sub-categories were defined: part-time due to basic disease (PT1); part-time not due to basic disease (PT2); part-time reason not known (PT3).
Time frame: Baseline, End of study (up to cut-off date, [19 Nov 2012])
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: FT, EOS: FT | 3 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: FT, EOS: PT1 | 2 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: FT, EOS: PT2 | 1 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: FT, EOS: PT3 | 0 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: FT, EOS: U/R | 24 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT1, EOS: FT | 3 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT1, EOS: PT1 | 3 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT1, EOS: PT2 | 0 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT1, EOS: PT3 | 0 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT1, EOS: U/R | 9 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT2, EOS: FT | 0 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT2, EOS: PT1 | 0 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT2, EOS: PT2 | 0 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT2, EOS: PT3 | 1 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT2, EOS: U/R | 5 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT3, EOS: FT | 0 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT3, EOS: PT1 | 0 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT3, EOS: PT2 | 0 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT3, EOS: PT3 | 0 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT3, EOS: U/R | 0 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: U/R, EOS: FT | 5 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: U/R, EOS: PT1 | 5 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: U/R, EOS: PT2 | 1 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: U/R, EOS: PT3 | 0 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: U/R, EOS: U/R | 199 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: Missing, EOS: FT | 0 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: Missing, EOS: PT1 | 0 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: Missing, EOS: PT2 | 0 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: Missing, EOS: PT3 | 0 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: Missing, EOS: U/R | 1 participants |
| Cilengitide + Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: Missing, EOS: Missing | 1 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT3, EOS: FT | 0 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: FT, EOS: FT | 6 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: U/R, EOS: PT3 | 0 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: FT, EOS: PT1 | 1 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT3, EOS: PT1 | 0 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: FT, EOS: PT2 | 0 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: Missing, EOS: PT2 | 0 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: FT, EOS: PT3 | 0 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT3, EOS: PT2 | 0 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: FT, EOS: U/R | 22 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: U/R, EOS: U/R | 191 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT1, EOS: FT | 2 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT3, EOS: PT3 | 0 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT1, EOS: PT1 | 1 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: Missing, EOS: U/R | 1 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT1, EOS: PT2 | 0 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT3, EOS: U/R | 0 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT1, EOS: PT3 | 0 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: Missing, EOS: FT | 0 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT1, EOS: U/R | 12 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: U/R, EOS: FT | 8 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT2, EOS: FT | 1 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: Missing, EOS: PT3 | 0 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT2, EOS: PT1 | 0 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: U/R, EOS: PT1 | 7 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT2, EOS: PT2 | 0 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: Missing, EOS: PT1 | 0 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT2, EOS: PT3 | 0 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: U/R, EOS: PT2 | 1 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: PT2, EOS: U/R | 4 participants |
| Temozolomide + Radiotherapy | Number of Participants With Change From Baseline in Work Status at End of Study | Baseline: Missing, EOS: Missing | 1 participants |
Secondary
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) and Lab Parameters
Time frame: Up to 50 months
Population: 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.
Secondary
Progression Free Survival (PFS) Time - Investigator and Independent Read
The PFS time is defined as the duration from randomization to either first observation of progressive disease (PD) or occurrence of death due to any cause. Investigator read is the assessment of all imaging by the treating physician at the local trial site and Independent Read is the assessment of all imaging centrally by an Independent Review Committee (IRC). Investigator's assessed progression according to MacDonald criteria and IRC by Response Assessment in Neuro-Oncology Working Group (RANO) criteria using Gadolinium-enhanced magnetic resonance imaging. Investigator and IRC read: Progression is defined as greater than 25 percent increase in the sum of the product of the largest perpendicular diameters of enhancing tumor compared to the smallest prior sum, or Worsening of an evaluable lesion(s),or Marked increase in T2/FLAIR non-enhancing lesions (IRC only) or Any new lesion
Time frame: Time from randomization to disease progression, death or last tumor assessment, reported between day of first participant randomized, that is, Sep 2008 until cut-off date, (19 Nov 2012)
Population: ITT population included all the participants who were randomized to study treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cilengitide + Temozolomide + Radiotherapy | Progression Free Survival (PFS) Time - Investigator and Independent Read | PFS Time: Investigator read | 13.5 Months |
| Cilengitide + Temozolomide + Radiotherapy | Progression Free Survival (PFS) Time - Investigator and Independent Read | PFS Time: Independent read | 10.6 Months |
| Temozolomide + Radiotherapy | Progression Free Survival (PFS) Time - Investigator and Independent Read | PFS Time: Investigator read | 10.7 Months |
| Temozolomide + Radiotherapy | Progression Free Survival (PFS) Time - Investigator and Independent Read | PFS Time: Independent read | 7.9 Months |
Secondary
Time to Maximum Plasma Concentration (Tmax)
The Tmax for cilengitide was calculated by non-compartmental analysis using the computer program WinNonlin, Version 6.2.1.
Time frame: Day 1 of Week -1
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cilengitide + Temozolomide + Radiotherapy | Time to Maximum Plasma Concentration (Tmax) | 1.029 hours | Standard Deviation 0.401 |