Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase II, Multicenter, Randomized, Non-Comparative Clinical Trial to Evaluate the Efficacy and Safety of Bevacizumab Alone or in Combination With Irinotecan for Treatment of Glioblastoma Multiforme in First or Second Relapse
Brief Summary: This is a Phase II, open-label, multicenter, randomized, non comparative study consisting of two concurrent single-arms. Approximately 160 subjects will be randomized in a 1:1 ratio to Arm 1 (bevacizumab alone) or Arm 2 (bevacizumab + irinotecan).


Options:
A: Inclusion Criteria:

* Signed Informed Consent Form
* Age ≥ 18 years
* Histologically confirmed GBM in first or second relapse
* Radiographic demonstration of disease progression following prior therapy
* Bi-dimensionally measurable disease with a minimum measurement of 1 cm (10 mm) in one diameter on MRI performed within 14 days prior to first treatment (Day 0)
* An interval of ≥ 4 weeks since prior surgical resection
* Prior standard radiation for GBM
* Prior chemotherapy: first-relapse subjects
* Prior chemotherapy: second-relapse subjects
* Recovery from the effects of prior therapy, including the following: 4 weeks from cytotoxic agents (except 6 weeks from nitrosoureas, 3 weeks from procarbazine, 2 weeks from vincristine); 4 weeks from any investigational agent; 1 week from non-cytotoxic agents; 8 weeks from radiotherapy to minimize the potential for MRI changes related to radiation necrosis that might be misdiagnosed as progression of disease, or 4 weeks if a new lesion, relative to the pre-radiation MRI, develops that is outside the primary radiation field
* Prior therapy with gamma knife or other focal high-dose radiation is allowed but the subject must have subsequent histologic documentation of recurrence, unless the recurrence is a new lesion outside the irradiated field
* Karnofsky performance status ≥ 70
* Life expectancy \> 12 weeks
* Use of an effective means of contraception in males and in females of childbearing potential
* Ability to comply with study and follow-up procedures

Exclusion Criteria:

* Prior treatment with irinotecan, bevacizumab, or another VEGF or VEGFR-targeted agent
* Prior treatment with prolifeprospan 20 with carmustine wafer
* Prior intracerebral agents
* Need for urgent palliative intervention for primary disease (e.g., impending herniation)
* Evidence of recent hemorrhage on baseline MRI of the brain with the following exceptions: Presence of hemosiderin; Resolving hemorrhagic changes related to surgery; Presence of punctate hemorrhage in the tumor
* Received more than two treatment regimens for Grade III and/or Grade IV glioma
* Blood pressure of \> 150 mmHg systolic and \> 100 mmHg diastolic
* History of hypertensive encephalopathy
* New York Heart Association (NYHA) Grade II or greater CHF
* History of myocardial infarction or unstable angina within 6 months prior to Day 0
* History of stroke or transient ischemic attack within 6 months prior to study enrollment
* Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis within 6 months prior to Day 0
* Evidence of bleeding diathesis or coagulopathy
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0
* History of intracerebral abscess within 6 months prior to Day 0
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study
* Minor surgical procedures (excluding placement of a vascular access device), stereotactic biopsy, fine needle aspirations, or core biopsies within 7 days prior to Day 0
* Serious non-healing wound, ulcer, or bone fracture
* Pregnancy (positive pregnancy test) or lactation
* Known hypersensitivity to any component of bevacizumab
* History of any other malignancy within 5 years (except non-melanoma skin cancer or carcinoma in situ of the cervix)
* Pregnant or nursing females
* Unstable systemic disease, including active infection, uncontrolled hypertension, or serious cardiac arrhythmia requiring medication
* Subjects unable to undergo an MRI with contrast
B: 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
C: DISEASE CHARACTERISTICS: Histologically confirmed newly diagnosed glioblastoma multiforme by biopsy or surgical resection Grade IV disease Initial diagnosis no greater than 6 weeks prior to study

PATIENT CHARACTERISTICS: Age: 18 to 70 Performance status: WHO 0-2 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) AST or ALT less than 2.5 times ULN Alkaline phosphatase less than 2.5 times ULN No chronic hepatitis B or C Renal: Creatinine no greater than 1.5 times ULN Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No known HIV infection No medical condition that would interfere with oral medication intake (e.g., frequent vomiting or partial bowel obstruction) No other prior or concurrent malignancy except surgically cured carcinoma in situ of the cervix or nonmelanoma skin cancer No serious medical, psychological, familial, sociological, or geographical condition that would preclude study

PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent filgrastim (G-CSF), sargramostim (GM-CSF), or epoetin alfa No concurrent biologic therapy No concurrent immunotherapy Chemotherapy: No prior chemotherapy No other concurrent chemotherapy Endocrine therapy: At least 14 days of prior corticosteroids at a stable dose required Concurrent corticosteroids allowed Radiotherapy: No prior radiotherapy No concurrent stereotactic boost radiotherapy Surgery: See Disease Characteristics No concurrent surgery for tumor debulking Other: No other concurrent investigational drugs
D: 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

Answer: A