Study of Tesevatinib Monotherapy in Patients With Recurrent Glioblastoma

Inclusion Criteria: 1. Willingness and ability to provide written informed consent and to comply with the study protocol as judged by the investigator 2. Age ≥ 18 years old 3. Kamofsky performance status ≥70% 4. Stable or decreasing dose of corticosteroids within 5 days prior to study 5. enrollment. 5. For women who are not postmenopausal (i.e., \< 12 months after last menstruation) or surgically sterile (absence of ovaries and/or uterus) and who are sexually active: agreement to use an adequate method of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly) during the treatment period and for at least 6 months after the last dose of study drug. 6. For male patients who are sexually active and who are partners of premenopausal women: agreement to use a barrier method of contraception during the treatment period and for at least 6 months after the last dose of study drug. 7. Histologically confirmed glioblastoma. A local pathology report constitutes adequate documentation of histology for study inclusion. Patients with an initial diagnosis of a lower-grade glioma are eligible if a subsequent biopsy was determined to be glioblastoma. 8. First recurrence after concurrent or adjuvant chemoradiotherapy. Imaging confirmation of first tumor progression or regrowth as defined by the RANO criteria . A minimum of 12 weeks must have elapsed from the completion of radiotherapy to study entry to minimize the potential for MRI changes related to radiation necrosis that might be misdiagnosed as progression of disease, unless there is a new lesion outside the radiation field or unequivocal evidence of viable tumor on histopathological sampling. 9. Prior treatment with TMZ for low grade glioma or glioblastoma. 10. No more than one prior line of systemic treatment for glioblastoma. Concurrent and adjuvant TMZ-based chemotherapy, including the combination of TMZ with an investigational agent, is considered one line of therapy. 11. Prior therapy with gamma knife or other focal high-dose radiotherapy is allowed, but the patient must have subsequent histologic documentation of recurrence, unless the recurrence is a new lesion outside the irradiated field. 12. Recovery from the toxic effects of prior therapy, with a minimum time of: 1. ≥ 28 days elapsed from the administration of any prior cytotoxic agents, except ≥ 14 days from vincristine, ≥ 21 days from procarbazine, and ≥ 42 days from nitrosureas 2. ≥ 28 days elapsed from the administration of any investigational agent 3. ≥ 14 days elapsed from administration of any non-cytotoxic agent (e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid) 13. Patients who have undergone recent surgery for recurrent or progressive tumor are eligible provided that: 1. Surgery must have confirmed the recurrence 2. There must be residual disease 3. A minimum of 28 days must have elapsed from the day of surgery to first dose of the study drug. For core or needle biopsy, a minimum of 7 days must have elapsed prior to study entry 14. Availability of formalin-fixed paraffin-embedded tumor tissue diagnostic of glioblastoma. Exclusion Criteria: 1. Concurrent therapeutic intervention (including radiation therapy and NovoTTF). 2. Prior exposure to EGFR inhibitors. 3. Prior exposure to bevacizumab or other VEGF- or VEGF-receptor-targeted agent within 8 weeks of study start. 4. Prior treatment with prolifeprospan 20 with carmustine wafer. 5. Prior intracerebral agent. 6. Evidence of recent hemorrhage on baseline MRI of the brain. However, patients with clinically asymptomatic presence of hemosiderin, resolving hemorrhagic changes related to surgery, or presence of punctuate hemorrhage in the tumor are eligible. 7. Need for urgent palliative intervention for primary disease (e.g., rapidly increasing intracranial pressure, impending herniation, uncontrolled seizures). 8. Hematology: ANC \< 1.5 x109/L; Plt \< 100 x109/L Hgb \< 9.0 g/dL within 7 days prior to enrollment. The use of transfusion or other intervention to achieve Hb ≥ 9 g/dL is acceptable. 9. T.Bili. ≥ 1.5 x ULN (except in patients diagnosed with Gilbert's disease). 10. AST(SGOT), ALT(SGPT), or alkaline phosphatase (ALP) ≥ 2.5 x ULN. 11. S. Creat. \> 1.5 x ULN. 12. K+ or Mg+ \< LLN. 13. In the absence of therapeutic intent to anticoagulate the patient: INR \> 1.5 or PT \> 1.5 xULN or aPTT \> 1.5 xULN Therapeutic anticoagulation. 14. Known contraindication to MRI, such as cardiac pacemaker, shrapnel or ocular foreign body. 15. Used any prescription medication during the prior 2 weeks that the investigator judges is likely to interfere with the study or to pose an additional risk to the patient in participating, specifically inhibitors or inducers of cytochrome P450 (CYP)3A4 (refer to Appendix 5). A stable regimen (≥ 4 weeks) of antidepressants of the selective serotonin re-uptake inhibitor (SSRI) class is allowed (common SSRIs include escitalopram oxalate, citalopram, fluvoxamine, paroxetine, sertraline, and fluoxetine). 16. Taking any drugs associated with torsades de pointes or known to moderately or severely prolong the QTc(F) interval 17. History of torsades de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (\< 50 bpm), heart block (excluding first degree block, being PR interval only), or congenital long QT syndrome. Patients with a history of atrial arrhythmias should be discussed with the Medical Monitor. 18. Uncontrolled diabetes, as evidenced by fasting serum glucose level \>200 mg/dL 19. New York Heart Association (NYHA) Grade II or greater congestive cardiac failure. 20. Has marked prolongation of QTc(F) interval at screening or baseline (QTc\[F\] interval \> 470 msec) using the Fridericia method of correction for heart rate. 21. History of myocardial infarction (within 12 months) or unstable angina (within 6 months) prior to study enrolment. 22. History of stroke or transient ischemic attacks within 6 months prior to study enrolment. 23. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to study enrolment. 24. Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation). 25. History of intracranial abscess within 6 months prior to study enrolment. 26. History of another malignancy in the previous 3 years, with a disease-free interval of \< 3 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. 27. Evidence of any active infection requiring hospitalization or IV antibiotics within 2 weeks prior to study enrolment. 28. Known hypersensitivity to any excipients of tesevatinib. 29. Inability to swallow or absorb orally-administered medication.