Regorafenib With Temozolomide With or Without RT in MGMT-Methylated, IDH Wild-type GBM Patients

Exclusion Criteria

• •Received any prior treatment for glioma including:
• •1. Prior prolifeprospan 20 with carmustine wafer.
• •2. Prior intracerebral agent.
• •3. Prior radiation treatment for GBM or lower-grade glioma.
• •4. Prior chemotherapy or immunotherapy for GBM or lower-grade glioma.
• •5. NOTE: 5-aminolevulinic acid-mediated photodynamic therapy and Flourcrescein administered prior to surgery to aid in optimal surgical resection is not considered a chemotherapy agent.
• •Patients who performed biopsy as surgical approach of glioblastoma.
• •Patients who 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).
• •Patients who are receiving additional, concurrent, active therapy for GBM outside of the trial.
• •Disease located outside of the brain (e.g. brainstem and leptomeningeal disease).
• •Candidate for urgent palliative intervention for primary disease (e.g., impending herniation) as judged by the Investigator
• •History of allergy or hypersensitivity to any of the study treatments or any of their excipients.
• •In the presence of therapeutic intent to anticoagulate the patient: INR or PT and aPTT not within therapeutic limits (according to the medical standard in the institution). NOTE: Per American Society of Clinical Oncology (ASCO) guidelines, use of low-molecular-weight heparin (LMWH) should be the preferred approach.
• •Unable or unwilling to undergo brain MRI scans with intravenous (IV) gadolinium.
• •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.
• •Serious, non-healing wound, ulcer, bone fracture, or abscess.
• •Any cerebrovascular accident (including transient ischemic attacks) within the last 6 months prior to initiation of study treatment.
• •Have an ongoing infection with severity of Grade 2 or above (CTCAE 5.0)
• •Any hemorrhage or bleeding event that is ≥ Grade 3 based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE), Grade 2 intracranial hemorrhage, or persistent thrombotic/embolic event within 4 weeks prior to the start of study medication.
• •Uncontrolled or severe cardiac disease (e.g., history of unstable angina, myocardial infarction, coronary stenting, or bypass surgery within the last 6 months prior to initiation of study treatment), symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia (including atrial flutter/fibrillation), requirement for inotropic support or use of devices for cardiac conditions (e.g., pacemakers/defibrillators), or hypertension (participants with systolic blood pressure\[BP\] of \> 160 mmHg or diastolic BP of \> 100 mmHg despite optimal medical management are to be excluded).
• •History of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis, or symptomatic pleural effusion.
• •Active, known, or suspected auto-immune disease, including systemic lupus erythematosus, Hashimotos thyroiditis, scleroderma, polyarteritis nodosa, or auto-immune hepatitis.
• •Known history of hepatitis B, human immunodeficiency virus (HIV), or active hepatitis C infection requiring treatment with antiviral therapy. Note: HIV testing is not required in the absence of clinical suspicion.
• •History of bleeding diathesis (irrespective of severity).
• •Uncontrolled intercurrent illness including (e.g., symptomatic ascites), but not limited to ongoing or active infection.
• •Persistent ≥ Grade 3 Lipase (\> 2.0 - 5.0 x upper limit of normal \[ULN\] with signs or symptoms; \> 5.0 x ULN and asymptomatic).
• •Persistent proteinuria\> 3.5 g/24 hours measured by urine protein creatinine ratio from a random urine sample (≥ Grade 3, CTCAE 5.0)
• •Have any malabsorbition condition.
• •Any condition that could make the subject noncompliant with the study procedures and/or study requirements, as judged by the Investigator (for example: cognitive impairment, psychiatric illness, etc).