This phase IB/II trial is designed to investigate the safety and survival benefits for patients with recurrent grade-4 with unmethylated MGMT promoter treated with Bortezomib and Temozolomide in a specific schedule.
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
Hypersensitivity to Bortezomib, boron, or mannitol
Any contraindications for use of temozolomide
Peripheral neuropathy ≥ grade 2
Previous treatment with bevacizumab or lomustine alone or as a combination therapy for ralapsed glioblastoma (PCV as primary treatment of low grade glioma, before development of glioblastoma, is allowed)
Sequential
Bortezomib and Temozolomide Phase IB
DrugIn the Phase IB of the study the following dose escalation of TMZ will be performed: The first cohort of 3 patients will receive 150 mg/m2 of IMP (TMZ) for 5 days q4w. If one patient in this cohort develops a dose limiting toxicity, another cohort of 3 patients will be treated at the same dose level until 2 or more patients in the group of 3-6 develop DLT.
Bortezomib and Temozolomide Phase II
DrugThe patientes will be treated with the maximum recommended starting dose of Temozolomide and Bortezomib established in the IB phase of the study
Bortezomib-Temozolomide Maximum tolerated dose
En intra- and inter-patient dose escalation period of TMZ administered after Bortezomib
Overall survival
Overall survival at 1 year
Progression free survival
Progression free survival at 6 months
Time to progression
Median time
Biomarkers of treatment response
Identification of novel tumor biomarkers by determining physiological, molecular and biochemical changes in blood and tumor tissue that correlate with treatment responses
Tumour responses
Assessed by contrast enhanced MRI according to RANO criteria
Clinical response
Assessment of the neurologic status according to NANO criteria
Toxicity assessment
SAE, all grades hematologic and non hematologic toxicity
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Haukeland University Hospital
Lead sponsor
Oslo University Hospital
Collaborator
St. Olavs Hospital
Collaborator
University Hospital of North Norway
Collaborator
University of Bergen
Collaborator
University of Bonn
Collaborator
University of Oslo
Collaborator
