Due to conflicting data on the optimal moment to start TMZ chemotherapy and the impact of prolongation of the adjuvant phase with TMZ, the ANOCEF (Association des Neuro-Oncologues d'Expression Francophone) group proposes this randomized trial comparing an intensified arm (early TMZ and extended adjuvant TMZ until toxicity, progression or patient refusal) versus the classical EORTC regimen as control (RT and concomitant TMZ started 4-6 weeks after surgery followed by a number of adjuvant TMZ cycles strictly limited to 6) for primary GBM adult patients.

Inclusion Criteria:

• Patient ≥18 years old
• Histological diagnosis of de novo GBM (extemporaneous diagnosis or standard pathological examination). In case of extemporaneous diagnosis, the patient can be included. If the diagnosis is not confirmed, the patient will be withdrawn from study.
• Time between initial surgery/biopsy and planned start of treatment (if allocated to the experimental arm) ≤ 15 days (ideally in the first 7 days)
• Karnofsky performance status (KPS) ≥ 60%, or KPS <60% only related to glioma-related motor paresis.
• Adequate biological functions
• Common toxicity criteria (CTC) non hematological adverse events ≤ Grade 1 (except for alopecia, nausea, vomiting and neurological symptoms)
• Females of child bearing potential must have a negative serum or urine pregnancy test within 7 days prior to initiation of treatment. Sexually active patients must agree to use adequate and appropriate contraception while on study drug and for 6 months after stopping the study drug.
• Standard radiation therapy deemed feasible (60 Gy, 30 fractions)
• Time interval of less than 43 days between initial surgery/biopsy and planned start of radiation therapy
• Written informed consent

Exclusion Criteria:

• Secondary or recurrent glioblastoma (GBM)
• Planned use of tumor-treating electric fields
• Planned use of Carmustine implants
• Prior malignancy in the last 5 years before inclusion or concomitant
• Severe myelosuppression
• Known hypersensitivity to any of the study drugs, study drug classes, excipients in the formulation or to dacarbazine (DTIC)
• Current or recent treatment with another experimental drug or patients included in a clinical therapeutic trial (in the 30 days prior to inclusion).
• Known current viral hepatitis, HIV infection or current active infectious disease
• Inability to swallow oral medications or any mal-absorption condition
• Pregnant or breastfeeding patients.
• Inability to comply with medical follow-up of the trial (geographical, social or psychic reasons)
• Person under guardianship or curatorship