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

The primary aim of the study

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)