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:

* Histologically confirmed WHO grades 3 to 4 malignant glioma
* Diagnosed recurrence or progression by clinical or radiological evidence
* Fit for intraarterial infusion and intravenous chemotherapy
* Adequate hepatic, renal, and hematologic function.
* Legal age ≥18 years
* Life expectancy ≥12 weeks
* Eastern Cooperative Oncology Group performance (ECOG) ≥2
* Chemotherapy completion ≥4 weeks prior and recovery from drug induced toxicities.

Exclusion Criteria:

* Active pregnancy
* Prior gene therapy
* Second primary tumor
* Gravidity, lactation, hypersensitivity to antiviral drugs, immunologic deficit, active uncontrolled infections
* Requiring treatment with warfarin or any other anticoagulants
B: 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
C: Inclusion Criteria:

* unifocal, supratentorial recurrent glioma
* contrast enhancement on T1-weighted MRI and/or Amino-Acid-PET-positive high-grade tumor areas
* indication re-irradiation
* age ≥ 18 years of age
* Karnofsky Performance Score ≥60
* For women with childbearing potential, (and men) adequate contraception.
* Ability of subject to understand character and individual consequences of the clinical trial
* Written informed consent (must be available before enrolment in the trial)

Exclusion Criteria:

* Multifocal Glioma or Gliomatosis cerebri
* refusal of the patients to take part in the study
* previous re-irradiation or prior radiosurgery or prio treatment with interstitial radioactive seeds
* time interval of \< 6 months after primary radiotherapy
* Patients who have not yet recovered from acute toxicities of prior therapies
* Known carcinoma \< 5 years ago (excluding Carcinoma in situ of the cervix, basal cell carcinoma, squamous cell carcinoma of the skin) requiring immediate treatment interfering with study therapy
* Pregnant or lactating women
* Participation in another clinical study or observation period of competing trials, respectively.
D: Inclusion Criteria:

* Local recurrence of GBM (WHO grade IV) and either not eligible for tumor resection or with macroscopic residual tumor after resection of recurrent GBM
* Recurrent tumor visible on AA-PET and MRI-T1-Gd with the diameter measuring 1 cm to 6 cm by either technique
* Target volume definition possible according to both study arms
* Previous radiation therapy of the primary with a maximal total dose 60 Gy
* At least 9 months since the end of pre-irradiation and randomisation
* At most 2 prior chemotherapy regimes
* Start of radiation therapy possible within 2 weeks from AA-PET
* Karnofsky Performance Score (KPS) ≥ 70%
* Age ≥ 18 years
* Written informed consent (IC) obtained

Exclusion Criteria:

* - No histological confirmation of Glioma at initial diagnosis)
* Recent (≤ 4 weeks before IC) histological result showing no tumor recurrence
* No recurrent tumor detectable on last AA-PET or MRI-T1-Gd
* Technical impossibility to use existing AA-PET for RT-planning
* No prior radiation treatment to the primary tumor
* less than 9 months between the end of first radiation treatment and randomisation
* more than 2 previous chemotherapy regimes or previous treatment with Avastin or other molecular targeted therapies
* less than 2 weeks between application of chemotherapy and randomisation
* additional chemotherapy or molecular targeted therapy or further surgery planned before diagnosis of further tumor progression after study intervention
* pregnancy, nursing or patient not willing to prevent pregnancy during treatment

Answer: B