Study of Tesevatinib Monotherapy in Patients With Recurrent 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.