This study will test the hypothesis that prolonged adjuvant Temozolomide (TMZ) may delay relapses in patients with glioblastoma compared to the standard care consisting in observation with brain MRI every 3 months and rechallenging with TMZ at relapse (Stop and Go arm).

Inclusion Criteria:

1. Patients with histologically confirmed diagnosis of GBM
2. Availability of pre-treatment GBM tissue to determine the activation status of MGMT gene is not mandatory but strongly recommended
3. Patients must have received radiation and TMZ for 6 weeks followed by 6 months of TMZ. Randomization should be performed within the 6 weeks after the last chemotherapy.
4. A brain MRI with or without a PET-Scan-methionine must be performed before enrolment.
5. Age ≥ 18 years
6. Karnofsky Performance status ≥ 60
7. Normal haematological functions: ANC ≥ 1.5 x 109cells/l, platelets ≥ 100 x 109 cells/l
8. Normal liver function: total bilirubin < 1.5 x ULN, alkaline phosphatase and transaminases (ASAT/ALAT) < 2.5 times the upper limit of the normal range
9. Serum creatinine < 1.5 x ULN
10. Clinically normal cardiac function without history of ischemic heart disease in the past 12 months. Absence of cardiac insufficiency NYHA grade III and IV, instable angina, arrhythmia
11. No previous or current malignancy (except treated basal or squamous cell skin carcinoma, cervix cancer or in situ carcinoma of the breast).
12. All patients (male and female) with reproductive potential must use effective contraception. Females must have a negative serum pregnancy test at entry to study.
13. Signed informed consent from the patient or legal representative must be obtained.

Exclusion Criteria:

All non inclusion criteria