Entry Detail
| General information | |
| Database: | DB00589 |
| Objective: | They evaluated the efficacy and safety of bosutinib, a tyrosine kinase inhibitor that potently inhibits Src and Abl, in patients with recurrent glioblastoma |
| Authors: | Taylor JW, et al |
| Title: | Phase 2 study of bosutinib, a Src inhibitor, in adults with recurrent glioblastoma. |
| Journal: | J Neurooncol |
| Year: | 2015 |
| PMID: | 25411098 |
| Trial Design | |
| Clinical Trial Id: | NCT01331291 |
| Agent: | bosutinib |
| Target: | Protooncogene tyrosineprotein kinase SRC Abl |
| Cancer Type: | Tumors of the nervous system |
| Cancer Subtype: | glioblastoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | openlabeled, dualarm, singleagent, study |
| Key Patients Feature: | Eligible patients (aged C18 years) had histologically confirmed GBM (World Health Organization grade IV astrocytoma); had received temozolomide and radiation as firstline therapy; had B2 prior systemic treatments; had Karnofsky performance status (KPS) C60 %, and had archivedtumor material available. In addition, recurrent GBMpatients enrolled on Arm A were candidates for resection. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | Arm A planned for 6 patients who were candidates for surgical resection to be given bosutinib for 79 days prior to resection. Arm B was a twostage designphase 2 trial targeting 30 patients. |
| Treatment Info: | pts were administered oral bosutinib 400 mg daily. Arm A planned for 6 patients who were candidates for surgical resection to be given bosutinib for 79 days prior to resection. Arm B was a twostage designphase 2 trial targeting 30 patients. |
| Primary End Point: | progression free survival at 6 months (PFS6) |
| Secondary End Point: | NA |
| Patients Number: | 36 |
| Trial Results | |
| DLT_MTD: | oral bosutinib 400 mg daily |
| Objective Response Rate: | Best objective response was stable disease in one patient (11.1 %). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 7.71 weeks (95 % CI 2.6-7.9) |
| Median OS A vs. C: | 50 weeks(95 % CI 2.9-NA) |
| Adverse Event(agent arm): | Seven patients (77.8 %) had treatmentrelated AEs of any grade and 2 (22.2 %) were grade C3. Including both arms, 3 (27.3 %) patients experienced dose holds for a median of 2.5 days (range 2-5). The most common AE of any grade was lymphopenia in 9 (81.8 %), fatigue in 6 (54.6 %), and nausea in 6 (54.6 %) |
| Conclusions: | Bosutinib monotherapy does not appear to be effective in recurrent glioblastoma. Hotheyver, Src remains a potential target based on its upregulation in tumor samples and role in glioma invasion. |