A multicenter, phase II, randomized, non-comparative clinical trial of radiation and temozolomide with or without vandetanib in newly-diagnosed glioblastoma patients
Mené sur 114 patients atteints d'un glioblastome récemment diagnostiqué, cet essai multicentrique de phase II évalue, du point de vue de la survie globale, de la survie sans progression et de la toxicité, l'intérêt d'ajouter le vandétanib à un traitement combinant une radiothérapie et le témozolomide
Purpose : Vandetanib, a tyrosine kinase inhibitor of KDR (VEGFR2), EGFR, and RET, may enhance sensitivity to chemotherapy and radiation. We conducted a randomized, non-comparative, phase II study of radiation (RT) and temozolomide (TMZ) with or without vandetanib in patients with newly diagnosed glioblastoma (GBM). Experimental Design : We planned to randomize a total of 114 newly diagnosed GBM patients in a ratio of 2:1 to standard RT and TMZ with (76 patients) or without (38 patients) vandetanib 100 mg daily. Patients with age ≥ 18, Karnofsky performance status (KPS) ≥ 60, and not on enzyme-inducing antiepileptics were eligible. Primary endpoint was median overall survival (OS) from the date of randomization. Secondary endpoints included median progression-free survival (PFS), 12-month PFS, and safety. Correlative studies included pharmacokinetics as well as tissue and serum biomarker analysis. Results: The study was terminated early for futility based on the results of an interim analysis. We enrolled 106 pts (36 in the RT/TMZ arm, 70 in the vandetanib/RT/TMZ arm). Median OS was 15.9 months [95% CI, 11.0 months, 22.5 months] in the RT/TMZ arm and 16.6 months [95% CI, 14.9 months, 20.1 months] in the vandetanib/RT/TMZ (log-rank p=0.75). Conclusions : The addition of vandetanib at a dose of 100 mg daily to standard chemoradiation in patients with newly diagnosed GBM or GS was associated with potential pharmacodynamic biomarker changes and was reasonably well tolerated. However, the regimen did not significantly prolong overall survival compared to the parallel control arm, leading to early termination of the study.