Bevacizumab in Recurrent Grade II and III Glioma (TAVAREC)

No more than one line of chemotherapy (concurrent and adjuvant temozolomide chemotherapy is considered one line of chemotherapy)

• If given, chemotherapy must have consisted of either temozolomide or PCV, and patients must be off chemotherapy treatment for more than 6 months without progression.

Absence of any cardiovascular disorder, including but not limited to:

• No history of myocardial infarction, unstable angina within 6 months prior to randomisation
• No "New York Heart Association" (NYHA) Grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication.
• No significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to randomisation
• No prior history of hypertensive crisis or hypertensive encephalopathy
• No inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 m Hg)

Absence of any thrombotic or hemorrhagic event, including but not limited to:

• No evidence of recent hemorrhage on MRI of the brain. However, patients with clinically asymptomatic presence of hemosiderin, resolving hemorrhagic changes related to surgery, and presence of punctate hemorrhage in the tumor are permitted entry into the study
• No history or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding.
• No arterial or venous thrombosis ≤ 12 months prior to randomization
• No history of stroke or TIAs within 6 months prior to randomization
• No history of pulmonary haemorrhage/haemoptysis ≥ grade 2 according to the NCI-CTCAE version 4.0 criteria within 1 month prior to randomization
• Absence of current or recent (within 10 days of first dose of Bevacizumab) use of aspirin (> 325 mg/day) or other NSAID with anti-platelet activity or treatment with dipyramidole, ticlopidine, clopidogrel or cilostaz.
• International normalized ratio (INR) > 1.5 ULN and activated partial thromboplastin time (aPTT) > 1.5 × the ULN. Patients using full-dose anticoagulants at baseline are excluded from the study; but prevention of thrombosis with low-dose anticoagulant is allowed

Absence of known hypersensitivity

• to any part of the Bevacizumab or Temozolomide formulations.
• to Chinese hamster ovary cell products or other recombinant human or humanized antibody.

No underlying or previous conditions that could interfere with treatment, including but not limited to:

• No history of intracranial abscess within 6 months prior to randomisation
• No clinically serious (as judged by the investigator) non-healing wounds, active skin ulcers or incompletely healed bone fracture.
• No history of active gastroduodenal ulcer(s).
• No history of abdominal fistula as well as non-GI fistula, gastrointestinal perforation or intraabdominal abscess within 6 months prior to inclusion.
• No evidence of active infection requiring hospitalization or antibiotics, within 2 weeks prior to randomisation.
• No other diseases, interfering with follow up.

Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized. In general, the decision for appropriate methods to prevent pregnancy should be determined by discussions between the investigator and the study subject. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal.

• Post menopause is defined as: amenorrhea ≥ 12 consecutive months without another cause or for women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL
• Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential.
• Women of child bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product.