Brief Summary: RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as lomustine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known which regimen of bevacizumab given together with lomustine is most effective in treating patients with glioblastoma multiforme in first recurrence. PURPOSE: The primary objective of this study is to investigate whether the addition of bevacizumab to lomustine improves overall survival (OS) in patients with recurrent glioblastoma compared to treatment with lomustine alone.

Detailed Description: OBJECTIVES: * To determine the therapeutic role of bevacizumab as well as the most favorable approach to treatment optimization for sequencing the combination of bevacizumab and lomustine in patients with glioblastoma multiforme in first recurrence. OUTLINE: This is a multicenter study. Patients are stratified according to institution, WHO performance status (0 vs \> 0), steroid administration (yes vs no), and largest diameter of tumor (≤ 40 mm vs \> 40 mm). Patients are randomized at 2:1 ratio to 1 of 2 treatment arms. * Arm 1: Lomustine 90 mg/m² every 6 weeks (cap. 160 mg) + bevacizumab 10 mg/kg every 2 weeks (at further progression treatment will be according to investigators discretion). In the absence of hematological toxicity \> grade 1 during the first cycle the dose of lomustine can be escalated to 110 mg/m² (cap 200 mg) in their second cycle. * Arm 2 (control arm): Lomustine single agent 110 mg/m² every 6 weeks (cap. 200 mg) (at further progression treatment will be according to investigators discretion). One cycle will be defined arbitrarily (due to the lomustine sequencing) as 6 weeks for all arms. Day 1 of a cycle will be the first day when medication is taken. Previously collected blood and tumor tissue samples are analyzed for MGMT methylation status, isocitrate dehydrogenase 1, and biomarkers of the VEGF pathway. Patients and their caregivers/relatives complete quality-of-life questionnaires (EORTC QLQ-C30 and EORTC-BN20) at baseline, at 12 weeks, and then every 12 weeks after completion of study therapy. Patients also undergo neurocognitive assessment at baseline, at 12 weeks, and then every 12 weeks after completion of study therapy. After completion of study treatment, patients are followed every 12 weeks.