Regorafenib in Patients With Relapsed Glioblastoma. IOV-GB-1-2020 REGOMA-OSS

Inclusion Criteria:

* Male or female ≥ 18 years of age
* Histologically confirmed glioblastoma (grade IV)
* First recurrence after adjuvant treatment (surgery followed by radiotherapy and temozolomide chemotherapy) in patients who have not received further therapeutic interventions
* World Health Organization (WHO) Performance status ≤ 1 (or Karnofsky performance status (KPS) ≥70)) before the start of the treatment
* Documented progression of disease as defined by RANO criteria at least 12 weeks after completion of radiotherapy, unless the recurrence is outside the radiation field or has been histologically documented.
* Documented progression of disease by a brain MRI scan done within 14 days before the start of treatment with Regorafenib.
* Stable or decreasing dosage of steroids for 7 days prior to the baseline MRI scan.
* Have adequate bone marrow function, liver function, and renal function, as measured by the following laboratory assessments conducted within 7 days prior to the initiation of study treatment:
* Hemoglobin \>9.0 g/dl
* Absolute neutrophil count (ANC) \>1500/mm3 without transfusions or granulocyte colony stimulating factor and other hematopoietic growth factors
* Platelet count ≥100,000/μl
* White blood cell count (WBC) \>3.0 x 109/L
* Total bilirubin \<1.5 times the upper limit of normal
* ALT and AST \<3 x upper limit of normal
* Serum creatinine \<1.5 x upper limit of normal
* Alkaline phosphatase \<2.5 x ULN (\<5 x upper limit of normal value)
* PT-INR/PTT \<1.5 x upper limit of normal
* Lipase ≤ 1.5 x the ULN
* Glomerular filtration rate ≥ 30 mL/min/1.73 m2
* TSH, fT3,fT4 within normal limits
* Patients may have undergone surgery for the recurrence; the histological report must document a glioblastoma recurrence. If operated:
* at least 28 days from the surgery is required prior to Regorafenib administration and patients should have fully recovered.

Exclusion Criteria:

* Have had prior treatment with regorafenib or any other VEGFR-targeting kinase inhibitor
* Have had systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and/or hormonal therapy within 4 weeks prior to initiation of treatment
* Recurrent disease located outside of the brain
* Have uncontrolled hypertension (systolic blood pressure \[SBP\] \> 140 mmHg or diastolic blood pressure \[DBP\] \> 90 mmHg) despite optimal medical management
* Have had a myocardial infarction \< 6 months prior to initiation of treatment with Regorafenib
* 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 treatment with Regorafenib
* Have either active or chronic hepatitis B or C requiring treatment with antiviral therapy
* 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)