A Study of Avastin (Bevacizumab) And Fotemustine in Patients With Recurrent Glioblastoma

• Progression-free Survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
• Overall Survival [ Time Frame: 9 months ] [ Designated as safety issue: No ]
• Objective Response Rate [ Time Frame: 9 months ] [ Designated as safety issue: No ]
• Median Progression-free Survival [ Time Frame: 9 months ] [ Designated as safety issue: No ]
• Median Overall Survival [ Time Frame: 9 months ] [ Designated as safety issue: No ]
• Safety (Incidence of Adverse Events) [ Time Frame: 9 months ] [ Designated as safety issue: No ]
• Quality of Life [ Time Frame: 9 months ] [ Designated as safety issue: No ]

This randomized, non-comparative study will evaluate the efficacy and safety of Avastin (bevacizumab) in patients with recurrent glioblastoma. Patients will be randomized to receive Avastin 10 mg/kg intravenously every 2 weeks or fotemustine 75 mg/m2 on days 1, 8 and 15, followed by, after a 5 weeks interval, 100 mg/m2 intravenously every 3 weeks. Treatment with fotemustine serves as a calibration arm and no formal efficacy comparison will be made between the two treatment arms. The anticipated time of study treatment is until disease progression or unacceptable toxicity.

• Drug: bevacizumab [Avastin]
  10 mg/kg every 2 weeks intravenously until disease progression or unacceptable toxicity
• Drug: fotemustine
  75 mg/m2 intravenously on days 1, 8 and 15 followed by, after a 5 weeks interval, 100 mg/m2 on day 1 of a 3-weeks cycle. Until disease progression or unacceptable toxicity

• Experimental: Investigational Arm
  Intervention: Drug: bevacizumab [Avastin]
• Experimental: Calibration Arm
  Intervention: Drug: fotemustine

Inclusion Criteria:

• Adult patients, >/=18 years of age
• Diagnosis of recurrent glioblastoma multiforme (Grade IV)
• Previous treatment with temozolomide and radiotherapy
• First recurrence after standard adjuvant treatment (surgery, followed by radiotherapy and chemotherapy)
• Adequate hematological, biochemical and organ functions

Exclusion Criteria:

• Previous treatment with Avastin or other anti-angiogenic drugs
• Residual relevant toxicity resulting from previous therapy
• Radiotherapy within the 3 months prior to the diagnosis of disease progression
• Chemotherapy in the previous 4 weeks
• Other active or inactive malignancies (except for carcinoma in situ of the cervix, of the prostate or basal cell carcinoma)
• Clinically significant cardiovascular diseases