• Histological diagnosis of MGMT promoter methylated, IDH wild type (WT) GBM with consistent local molecular pathology (repeat biopsy at recurrence is NOT required).

• First recurrence of GBM planned for systemic treatment as determined by local Multidisciplinary Team (MDT), including agreement of a Consultant Neuro-Radiologist that imaging changes are most in keeping with recurrence and not pseudo-progression. Patients with a prior recurrence treated by surgical resection alone are eligible at time of first recurrence planned for systemic treatment.

• Patients must have received initial first-line treatment with standard dose conventionally fractionated radiotherapy (i.e. 40 Gy in 15 fractions or 54-60 Gy in 28-33 fractions; other regimes may be considered in consultation with the ARISTOCRAT Trial Office) with concomitant and adjuvant TMZ.

‣ A minimum of 3 cycles of adjuvant TMZ must have been received.

⁃ A minimum of Stable Disease (SD) (or Partial Response (PR)/Complete Response (CR)) at the end of first-line treatment (measured by Response Assessment for Neuro-Oncology (RANO) criteria).

• ≥3 months since day 28 of the last cycle of TMZ.

• Karnofsky Performance Status ≥60.

• Adequate hematologic, renal, and hepatic function within 14 days prior to randomisation:

‣ Absolute neutrophil count (ANC) ≥1.5 x 109/L

⁃ Platelet count ≥100 x 109/L

⁃ Serum creatinine clearance (measured or calculated (using local standard practice)) \>30ml/min

⁃ Total serum bilirubin ≤1.5 x upper limit of normal (ULN)

⁃ Liver transaminases \<2.5 x ULN

• If surgery has been performed for first recurrence, then the wound must be adequately healed and there must be residual enhancing disease on MRI within 21 days of surgery or new enhancement at later follow up deemed suitable for systemic treatment.

• Recovered from previous treatment side-effects ≤ Grade 2.

• If on systemic steroids, must be on stable (≥7 days) or decreasing dose of steroids.

• Willing and able to provide trial-specific informed consent.

• Willing and able to comply with trial requirements.

• Age ≥16.

• Able to start treatment within 28 days of randomisation.