Phase 2 study of bosutinib, a Src inhibitor, in adults with recurrent glioblastoma

Journal of Neuro-oncology
Jennie W TaylorAndrew S Chi

Abstract

Tumor cell infiltration is a major mechanism of treatment escape in glioblastoma. Src is an intracellular tyrosine kinase that mediates tumor cell motility and invasiveness. We evaluated the efficacy and safety of bosutinib, a tyrosine kinase inhibitor that potently inhibits Src and Abl, in patients with recurrent glioblastoma. In this two-arm study, patients with histologically confirmed recurrent glioblastoma and ≤2 relapses, not previously treated with anti-vascular endothelial growth factor (VEGF) therapy, were administered oral bosutinib 400 mg daily. Arm A planned for 6 patients who were candidates for surgical resection to be given bosutinib for 7-9 days prior to resection. Arm B was a two-stage design phase 2 trial targeting 30 patients. The primary endpoint was progression-free survival at 6 months (PFS6) in Arm B. After 9 patients enrolled onto stage 1 of Arm B, 9 (100 %) patients progressed within 6 months. Therefore, the study met the pre-specified criteria for early closure and both Arms were closed. In Arm B, Median PFS was 7.71 weeks and median OS was 50 weeks. Best objective response was stable disease in one patient (11.1 %). Seven patients (77.8 %) had treatment-related AEs of any grade and 2 (22.2 %) were gra...Continue Reading

Associated Clinical Trials

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Jul 15, 2015·Oncology Letters·Quanchi ChenZhengdong Cai
Jul 15, 2016·Journal of Medicinal Chemistry·Timothy P Heffron
Jan 20, 2017·CNS Drugs·Mayur M Patel, Bhoomika M Patel
Dec 19, 2017·Journal of Drug Targeting·Khaled GreishHayley Nehoff
Apr 3, 2020·Archives of Pharmacal Research·Gayoung Kim, Young Tag Ko
Jun 18, 2020·Cancers·Claudia CirottiDaniela Barilà
Jun 16, 2017·American Journal of Physiology. Renal Physiology·Jun Wang, Shougang Zhuang
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Related Concepts

Bosutinib
Aniline Compounds
Antineoplastic Agents
Brain Tumor, Recurrent
Glioblastoma Multiforme
Neoplasm Recurrence, Local
Nitriles
Quinolines
Cox Proportional Hazards Models
Progression-Free Survival

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