Regorafenib in Relapsed Glioblastoma

Exclusion Criteria

• •Are taking strong cytochrome P (CYP) CYP3A4 inhibitors (eg, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole) or strong CYP3A4 inducers (eg, carbamazepine, phenobarbital, phenytoin, rifampin, St. John's Wort)
• •Radiotherapy within 12 weeks prior to the diagnosis of progression, if the lesion is in the radiation field,
• •Have had systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and/or hormonal therapy within 4 weeks prior to initiation of study treatment
• •Positioning of carmustin wafers during first or second surgery
• •Other active or inactive malignancy (except for carcinoma in situ of the cervix, of the prostate or basal cell carcinoma). Malignancy will be considered inactive if patients are in complete remission for at least 3 years prior to study entry
• •Have had prior treatment with regorafenib or any other VEGFR-targeting kinase inhibitor
• •Have had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of study treatment
• •Are pregnant
• •Are breastfeeding
• •Are unable to swallow oral tablets (crushing of study treatment tablets is not allowed)
• •Have congestive heart failure classified as New York Heart Association Class 2 or higher
• •Have had unstable angina (angina symptoms at rest) or new-onset angina ≤ 3 months prior to screening.
• •Have had a myocardial infarction \< 6 months prior to initiation of study treatment
• •Have cardiac arrhythmias requiring anti-arrhythmic therapy, with the exception of beta blockers or digoxin
• •Have uncontrolled hypertension (systolic blood pressure \[SBP\] \> 140 mmHg or diastolic blood pressure \[DBP\] \> 90 mmHg) despite optimal medical management
• •Have had arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), or pulmonary embolism within 6 months prior to the initiation of study treatment
• •Have an ongoing infection with severity of Grade 2 or above (NCI-CTCAE v 4.0)
• •Have a known history of human immunodeficiency virus infection
• •Have either active or chronic hepatitis B or C requiring treatment with antiviral therapy
• •Have a history of organ allograft
• •Have evidence or history of any bleeding diathesis (including mild hemophilia), irrespective of severity
• •Have had a hemorrhage or a bleeding event ≥ Grade 3 (NCI-CTCAE v 4.0) within 4 weeks prior to the initiation of study treatment
• •Have a non-healing wound, ulcer, or bone fracture
• •Have renal failure requiring hemodialysis or peritoneal dialysis
• •Have dehydration ≥ Grade 1 (NCI-CTCAE v 4.0)
• •Have interstitial lung disease with ongoing signs and symptoms at the time informed consent is obtained
• •Have persistent proteinuria \> 3.5 g/24 hours measured by urine protein creatinine ratio from a random urine sample (Grade 3, NCI-CTCAE v 4.0)
• •Have any other serious or unstable illness, or medical, psychological, or social condition, that could jeopardize the safety of the subject and/or his/her compliance with study procedures, or may interfere with the subject's participation in the study or evaluation of the study results
• •Have a known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs
• •Have any malabsorption condition
• •Recurrent disease located outside of the brain