Bortezomib and Temozolomide in Recurrent Grade-4 Glioma Unmethylated MGMT Promoter (BORTEM-17)

Inclusion Criteria: * Life expectancy \> 8 weeks * Histologically confirmed intracranial glioblastoma (GBM), with MGMT unmethylated promoter * Must submit an unstained paraffin block and/ or cryopreserved tumour tissue from surgical procedure * Radiologically (MRI) confirmed tumour relapse/progression ≥ 12 weeks since completed radiotherapy * Measurable recurrent tumor * Tumor not available for radio-surgery * If previously treated with gammaknife, at least one evaluable lesion outside the irradiated area is required, unless the time after the radiosurgery is 12 weeks or more * Written informed consent for study participation and tumour, blood sample collection obtained before performance of any study related procedure. * Karnofsky performance status ≥ 70 * WBC ≥ 3,000/mm\^3 * ANC ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 10 g/dL (transfusion allowed) * Bilirubin \< 2.5 times upper limit of normal (ULN) * serum aspartate aminotransferase (AST) \< 2.5 times ULN * Estimated GFR ≥ 60 mL/minute * Serum sodium \> 130 mmol/L * Serum potassium level within normal limit * Stable or reduced doses of corticosteroids for at least 1 week prior to enrolment * Negative pregnancy test no longer than 14 days prior to enrollment * Fertile patients and female partners with child bearing potential of male patients must use adequate contraception * Patients on EIAED must be transitioned to non-EAIED for ≥ 2 weeks * Unfractionated and/or low molecular weight heparin allowed *…