Phase II study of tivozanib, an oral VEGFR inhibitor, in patients with recurrent glioblastoma.

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2025 Background: Tivozanib, an oral, pure VEGFR tyrosine kinase inhibitor is an anti-angiogenesis drug which aims to modulate the tumor blood supply. This phase II study was designed to test the effectiveness of tivozanib on tumor vasculature in patients with recurrent GBM. Methods: Ten adult patients with recurrent GBM, median age of 62 (range 51-73), were enrolled on a Simon 2-stage design study and treated with tivozanib 1.5mg daily, 3 weeks on/1 week off in 28 day cycles. Brain MRI was done at baseline and after each cycle. The enhancing tumor and surrounding area of abnormal FLAIR hyperintensity were outlined and median tumor cerebral blood flow (CBF) and cerebral blood volume (CBV) values were derived from dynamic susceptibility contrast MRI to assess the performance of tivozanib. Vessel architectural imaging (VAI) was used to measure tumor vessel calibers and relative oxygen saturation. A t-test was used to compare baseline MRI parameters to the pre-cycle 3 visit. A univariate Cox model was used to test the association of each MRI parameter with time to progression. Results: Best MacDonald criteria responses were: CR (1), PR (1), SD (4), PD (4) and the median duration of response was only 3.6 mo (1.7-3.8mo) so the study was stopped per planned stopping rule. One patient was taken off study for unacceptable skin toxicity and nine patients for progressive disease. Given the dropout rate, only data up to cycle 3 was included in this analysis. There was no statistically significant change in enhancing tumor volume (p = 0.70), FLAIR volume (p = 0.31), or median CBV (p = 0.13) or median CBF (p = 0.54) within the enhancing tumor. Within the FLAIR hyperintensity, median CBV (p = 0.12) and median CBF (p = 0.41) also did not change significantly. No parameter was associated with time to tumor progression. VAI showed no change in vessel calibers or tissue oxygenation. Conclusions: Tivozanib was well tolerated but most patients progressed rapidly. The majority of patients had no significant change in tumor enhancement and perfusion imaging demonstrated insignificant changes in tumor and peritumoral blood volume, flow, vessel caliber, and oxygenation, suggesting that this anti-angiogenic agent had limited impact on brain tumor vasculature. Clinical trial information: NCT01846871.