In a phase I clinical trial of NCT03233152 that tested a combination of anti-CTLA-4 monoclonal antibody ipilimumab with a coadministered anti-PD-1 monoclonal antibody nivolumab in patients with recurrent GBM, a positive trend towards prolonged overall survival was observed (median OS = 38 weeks), with no significant change in PFS (11.7 weeks) when compared with historical controls of GBM patients treated with anti-VEGF therapy [ 276 ].
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The clinical trial that tested gefitinib with multitargeted tyrosine kinase inhibitor cediranib versus cediranib plus a placebo showed a trend on prolonged survival rates with patients administered with a combined scheme; however, the study was underpowered statistically, and more investigations should be performed in order to validate that hypothesis [ 199 ].
Two completed clinical trials that evaluated the coadministration of dasatinib with bevacizumab, versus bevacizumab alone or combined with the Stupp protocol, versus the Stupp protocol alone, did not reach statistical significance for the compared groups and, therefore, the results obtained were unreliable ( NCT00869401 ) [ 251 ].