The aim of the study was to explore the dose-limiting toxicity (DLT) and the maximum tolerable dose (MTD) of oral administration of TG02 capsules twice a week for 4 weeks.

Using the traditional 3 +3 design, 150 mg as the initial dose and 50 mg as the increasing interval of up to 250 mg, and oral administration on the 1st, 4th, 8th, 11th, 15th, 18th, 22nd and 25th day of each 28-day cycle. Phase I clinical study to evaluate the tolerance and pharmacokinetic parameters of oral TG02 capsules.

Inclusion criteria:

1. Age: 18 ~ 75 years old, both men and women.
2. Histologically proven glioblastoma or anaplastic astrocytoma that has failed from temozolomide treatment in the past.
3. According to RANO criteria, patients with clinically evaluated recurrence or progression with clearly measurable lesions.
4. If previous radiotherapy has been performed, it must be completed for a period of more than 3 months, or within 3 months but tumor progression occurs in the original radiation field or has been confirmed by histopathology. .
5. The first day of treatment was ≥ 2 weeks from the second surgery of recurrence, and the incision is healed in grade A.
6. ECOG 0 - 2 points, can swallow the drug and maintain oral administration.
7. The expected survival time was more than 3 months.
8. The hematopoietic function of bone marrow was adequate: ANC≥1.5×109/L，PLT≥100×109/L，Hb≥90 g/L；.
9. Patients who had previously undergone surgical resection were able to provide no less than 15 tumor tissue sections and pathological reports for the study.

Exclusion criteria

1. Other cytotoxic drugs were received within 28 days prior to the start of the study, or adverse reactions from previous systematic treatment have not recovered (except alopecia and pigmentation).
2. Bevacizumab was treated within 6 weeks before the start of the study.
3. Previous treatment with carmostine sustained-release implants or intracerebral implantation of radiotherapy.
4. A patient with a major seizure that cannot be effectively controlled by drugs.
5. MRI examinations cannot be performed (e.g. pacemakers, undesirable metal dentures, etc.).
6. Patients with severe impairment of liver and kidney function: ALT ≥ 2.5 ULN,AST ≥ 2.5 ULN in patients without liver metastasis; ALT ≥ 5 ULN,AST ≥ 5 ULN in patients with liver metastasis; Or TBIL ≥ 1.5 ULN, or Cr ≥ 1.5 ULN, or creatinine clearance ≤ 60 ml/ min calculated by Cockcroft-Gault formula;
7. Unstable or uncontrollable diseases or conditions related to or affecting cardiac function (e.g. unstable angina pectoris, congestive heart failure [NYHA > II], uncontrolled hypertension [diastolic blood pressure > 85 mmHg; systolic blood pressure >145 mmHg]), arrhythmia or prolonged QTc interval (male > 450 Ms; female > 470ms).
8. A history of arterial thromboembolism (such as stroke, transient ischemic attack, or myocardial infarction) within 6 months. Bleeding or hypercoagulable coagulation disorder occurred within 6 months prior to the first day of the study.
9. Active peptic ulcer or inflammatory bowel disease.
10. Active hepatitis, or HIV, Treponema pallidum infection.
11. Pregnant or breastfeeding.
12. Subjects who were unable to use adequate contraception during the study and for six months after the end of the study were unable to use adequate contraception.
13. Currently participating in another clinical trial or within 30 days of the last administration of the trial drug.
14. The subjects had conditions that affected their provision of written informed consent and / or compliance with the research process.
15. There were cases in which any other investigator did not consider it appropriate to join the group.