Multi-kinase Inhibitor TG02 (TG02) in Elderly Newly Diagnosed or Adult Relapsed Patients With Anaplastic Astrocytoma or Glioblastoma.

Specifics for groups A and B

• Newly diagnosed glioblastoma or anaplastic astrocytoma, IDH1R132H-non-mutant by immunohistochemistry locally assessed, with formalin-fixed, paraffin-embedded (FFPE) tissue available for central MGMT testing and optional biomarker studies (treatment allocation will be performed based on centrally assessed MGMT result)
• Tumor debulking surgery, including partial resection
• Age > 65 and considered non-eligible for combination therapy (TMZ/RT→TMZ) in Investigator's opinion
• No prior RT with overlap of radiation fields with the planned RT in this study (Group A)
• No prior therapy for glioblastoma or anaplastic astrocytoma before surgery
• Brain MRI within 14 days before the first dose of TG02

Specifics for group C

• IDH1R132H-non-mutant glioblastoma or anaplastic astrocytoma at first relapse with tissue available from first surgery. [Per 2016 World Health Organization (WHO) classification, in patients older than 55 years of age at diagnosis with a histological diagnosis of glioblastoma, without a pre-existing lower grade glioma and with non-midline tumor location, immunohistochemical negativity for IDH1R132H suffices for classification as glioblastoma. In all other instances of diffuse gliomas, lack of IDH1R132H immunopositivity should be followed by IDH1 and isocitrate dehydrogenase 2 (IDH2) sequencing to detect or exclude other less common IDH mutations.]
• Brain MRI at the time of progression or 14 days before the first dose of TG02 and availability of last brain MRI before progression diagnosis for upload to the EORTC Imaging Platform for post-hoc central review of progression
• Diagnosis of recurrence more than 3 months after the end of RT for initial treatment
• Intention to be treated with standard TMZ/RT→TMZ for initial treatment (at least one dose of TMZ administered; RT alone or chemotherapy alone as initial treatment are not permitted)
• No discontinuation of TMZ for toxicity during first-line treatment
• No RT or stereotactic radiosurgery is allowed for the treatment of first recurrence prior to enrollment in this study
• Patient may have been operated for recurrence. If operated:
• surgery completed at least 2 weeks before initiation of TG02 and patients should have fully recovered as assessed by investigator. Criteria for full recovery include absence of active post-operative infection, recovery from medical complications (CTCAE grade 0 and 1 acceptable), and capacity for adequate fluid and food intake
• residual and measurable disease after surgery is not required but surgery must have confirmed the recurrence
• a post-surgery MRI should be available within 72 hours; the post-surgery MRI can be used as baseline if performed within 2 weeks prior to registration. If not, a baseline MRI has to be done within 2 weeks prior to registration
• For non-operated patients: recurrent disease must be at least one bi-dimensionally measurable contrast-enhancing lesion with clearly defined margins by MRI scan, with minimal diameters of 10 mm, visible on 2 or more axial slices 5 mm apart, based on a MRI scan done within 2 weeks prior to registration
• Age ≥ 18 years

All groups

• Karnofsky Performance Score (KPS) of 60-100
• Recovered from effects of debulking surgery, postoperative infection and other complications of surgery (if any) (CTCAE grade 0 and 1 acceptable)
• Adequate bone marrow, renal and hepatic function within the following ranges within 7 days before the first dose of TG02:
• white blood cell (WBC) ≥ 3 x109/L
• absolute neutrophil count (ANC) ≥ 1.5x109/L
• Platelet count of ≥ 100 x109/L independent of transfusion
• Hemoglobin ≥ 10 g/dl or ≥ 6.2 mmol/L
• Bilirubin ≤ 1.5 × upper limit of normal (ULN)
• Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN
• Cockcroft-Gault calculated or measured creatinine clearance of ≥ 30 mL/min
• No use of enzyme-inducing anti-epileptic drugs (EI-AED) within 7 days prior to the first dose of TG02
• Life expectancy > 8 week