Please select the eligibility criteria that correspond to the clinical trial below.
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)
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.


Options:
A: Key Inclusion Criteria:

* newly diagnosed glioblastoma
* World Health Organization (WHO) performance status less than or equal to (\<=2)
* stable or decreasing corticosteroid dose within 5 days prior to randomization

Key Exclusion Criteria:

* evidence of recent hemorrhage on postoperative magnetic resonance imaging (MRI) of brain
* any prior chemotherapy or immunotherapy for glioblastomas and low grade astrocytomas
* any prior radiotherapy to brain
* clinically significant cardiovascular disease
* history of greater than or equal to (\>=) grade 2 hemoptysis within 1 month prior to randomization
* previous centralized screening for Methylguanine-DNA methyltransferase (MGMT) status for enrollment into a clinical trial
B: 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 exclusion criteria could apply
C: Inclusion Criteria:

All the eligibility criteria must be met before registration :

* delay upper or equal to 14 days from stereotaxic biopsy and 28 days from surgical biopsy
* Histopathologically proven diagnosis of glioblastoma (WHO grade IV astrocytoma)
* Patient belonging to the RPA V class or associated
* only supratentorial glioblastoma
* Diagnosis must be obtained by a stereotactic or surgical biopsy
* Age between 18 and 70
* A contrast-enhanced MRI must be performed within 28 days prior to study registration
* Total or partial surgical resection deemed as not possible by a neurosurgeon
* Karnofsky Index (KI) performance status over 50
* Life expectancy of at least 3 months
* A stable dose of corticosteroid for at least 7 days to control intracranial pressure and neurological symptoms
* Adequate blood function : absolute neutrophil count \> 1.5 x 109/L, platelets count \> 100 x 109/L platelets; hemoglobin \> 10 g/dl after blood transfusion if required
* Adequate liver function: bilirubin \< 1.5 ULN (upper limit of normal), ALT and AST \< 2.5 ULN, Prothrombin rate \> 75 %
* Adequate renal function: creatinine \< 1.2 ULN; proteinuria test 0 or trace (or urine protein concentration \< 1g/24h if proteinuria test is + or ++).
* Negative pregnancy test for women of childbearing potential and adequate contraception for men and women.
* systolic arterial blood pressure at rest ≤ 170 mmHg
* Patient must have been informed and must have signed the specific informed consent form.
* holder of a coverage by the health insurance

Exclusion Criteria:

* patient belonging to the RPA III or IV
* prior malignant tumor in the recent 5 years or concomitant malignancy
* prior anti-tumoral chemotherapy or radiotherapy
* prior gross resection of the brain tumor
* patient receiving gliadel
* cardiovascular contra-indications to bevacizumab : prior angina pectoris, prior myocardial infarction, prior brain stroke, even transient, distal severe arteriopathy, uncontrolled high blood pressure
* anticomitial drug p450 cytochrome inductors
* other substances inducing p450 cytochrome
* proteinuria ≥ 1g/L
* concurrent anticoagulant or platelet anti-aggregant treatment
* congenital haemorrhagic pathology (haemophilia, Willebrandt)
* sign of brain haemorrhage on the RMI initial exam
* non resolved infectious disease
* non controlled arterial hypertension (≥170 mmHg)
* intracranial high pressure not controlled by a stable dose of steroids for at least 7 days
* pregnancy or refusal of the contraception for women and men
* psychiatric, behavioural disorders or geographical situation precluding the administration or follow-up of the protocol (including claustrophobia)
* digestive haemorrhage and / or gastro-duodenal ulcer occurring in the last 3 months
* pregnant, nursing woman, or without contraception
* private individuals of freedom or under tutelage (including legal guardianship)
D: Inclusion Criteria:

* adult patients, 18-70 years of age;
* glioblastoma, confirmed histologically;
* no previous chemotherapy or radiotherapy for glioblastoma;
* non-methylated MGMT promoter in the tumor.

Exclusion Criteria:

* prior systemic treatment for glioblastoma multiforme;
* prior treatment with Avastin;
* significant cardiovascular disease;
* other active malignant disease.

Answer: B