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|Ref Type||Journal Article|
|Authors||Lee EQ, Kaley TJ, Duda DG, Schiff D, Lassman AB, Wong ET, Mikkelsen T, Purow BW, Muzikansky A, Ancukiewicz M, Huse JT, Ramkissoon S, Drappatz J, Norden AD, Beroukhim R, Weiss SE, Alexander BM, McCluskey CS, Gerard M, Smith KH, Jain RK, Batchelor TT, Ligon KL, Wen PY|
|Title||A Multicenter, Phase II, Randomized, Noncomparative Clinical Trial of Radiation and Temozolomide with or without Vandetanib in Newly Diagnosed Glioblastoma Patients.|
|Journal||Clinical cancer research : an official journal of the American Association for Cancer Research|
|Date||2015 Aug 15|
|Abstract Text||Vandetanib, a tyrosine kinase inhibitor of KDR (VEGFR2), EGFR, and RET, may enhance sensitivity to chemotherapy and radiation. We conducted a randomized, noncomparative, phase II study of radiation (RT) and temozolomide with or without vandetanib in patients with newly diagnosed glioblastoma (GBM).We planned to randomize a total of 114 newly diagnosed GBM patients in a ratio of 2:1 to standard RT and temozolomide with (76 patients) or without (38 patients) vandetanib 100 mg daily. Patients with age ≥ 18 years, 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.The study was terminated early for futility based on the results of an interim analysis. We enrolled 106 patients (36 in the RT/temozolomide arm and 70 in the vandetanib/RT/temozolomide arm). Median OS was 15.9 months [95% confidence interval (CI), 11.0-22.5 months] in the RT/temozolomide arm and 16.6 months (95% CI, 14.9-20.1 months) in the vandetanib/RT/temozolomide (log-rank P = 0.75).The addition of vandetanib at a dose of 100 mg daily to standard chemoradiation in patients with newly diagnosed GBM or gliosarcoma was associated with potential pharmacodynamic biomarker changes and was reasonably well tolerated. However, the regimen did not significantly prolong OS compared with the parallel control arm, leading to early termination of the study.|
|Molecular Profile||Treatment Approach|
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|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
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|IDH1 R132H||glioblastoma multiforme||sensitive||Temozolomide + Vandetanib||Phase II||Actionable||In a Phase II trial, Caprelsa (vandetanib), in combination with Temodar (temozolomide) and radiation therapy, demonstrated a significant increase in PFS and OS in glioblastoma patients harboring IDH1 R132H compared to glioblastoma patients without IDH1 R132H (PMID: 25910950).||25910950|
|Unknown unknown||glioblastoma multiforme||not applicable||Temozolomide + Vandetanib||Phase II||Actionable||In a Phase II trial, Caprelsa (vandetinib), in combination with radiation therapy and Temodar (temozolomide), demonstrated no difference in PFS and OS when compared to radiation therapy and Temodar (temozolomide) alone in glioblastoma patients (PMID: 25910950).||25910950|