Clinical Study of Apatinib Combined With Temozolomide in the Treatment of Uncontrolled or Repeated High-grade Gliomas

Inclusion Criteria:

* 1\. Age: 18 \~ 70 years old, male or female; 2. ECOG score: 0-2 points; 3. Expected survival time ≥ 3 months; 4. Patients diagnosed with high-grade (WHO III, IV) gliomas by pathology, and patients whose disease recurrence is judged by contrast imaging, have at least one measurable lesion on the skull magnetic resonance; 5. Patients who have not been controlled or relapsed after previous first-line standard treatment; 6. The main organs function normally, that is, they meet the following standards:

  1. The blood routine examination standards must be met (no blood transfusion and blood products within 14 days, no correction using G-CSF and other hematopoietic stimulating factors)

     1. HB≥90 g / L;
     2. ANC≥1.5 × 109 / L;
     3. PLT≥80 × 109 / L;
  2. Biochemical inspection must meet the following standards:

     1. TBIL \<1.5ULN;
     2. ALT and AST \<2.5ULN, but \<5ULN for patients with liver metastases;
     3. Serum Cr≤1.25ULN or endogenous creatinine clearance rate\> 45 ml / min (Cockcroft-Gault formula); 7. Women of childbearing age must have taken reliable contraceptive measures or performed a pregnancy test (serum or urine) within 7 days before enrollment, with negative results, and be willing to use appropriate methods during the test and 8 weeks after the last dose contraception. For men, consent must be given to appropriate contraception or surgical sterilization during the trial and 8 weeks after the last test drug administration; 8. Participants voluntarily joined the study and signed informed consent, with good compliance and cooperation with follow-up.

Exclusion Criteria:

\- 1. Factors that significantly affect oral drug absorption, such as inability to swallow, chronic diarrhea, and intestinal obstruction; 2. Patients with urinary protein positive (urinary protein detection 2+ or more, or 24-hour urine protein quantification\> 1.0g); 3. Patients with hypertension who cannot be reduced to normal range with antihypertensive medication (systolic blood pressure\> 140 mmHg, diastolic blood pressure\> 90 mmHg) 4. Concurrent active cancer that requires non-surgical treatment (eg chemotherapy, radiotherapy, adjuvant therapy) 5. Previously suffered severe cardiovascular disease: myocardial ischemia or myocardial infarction of grade Ⅱ or above, poorly controlled arrhythmia (including QTc interval ≥450 ms for men, ≥470 ms for women); according to NYHA standards, grade Ⅲ ～ Ⅳ Cardiac insufficiency, or color Doppler ultrasound examination of the left ventricular ejection fraction (LVEF) \<50%; 6. For previous symptoms of cerebral hemorrhage of grade 2 or higher, bleeding in other parts of grade ≥CTCAE grade 3 occurred within 4 weeks before the first use of the study drug; 7. Abnormal blood coagulation function (International Normalized Ratio of Prothrombin Time (INR)\> 1.5 ULN or Prothrombin Time (PT)\> ULN + 4 seconds or APTT\> 1.5 ULN), with bleeding tendency 8. Patients who are receiving thrombolytic or anticoagulant therapy and treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or its analogues; small-dose prophylaxis is allowed for preventive purposes provided that INR is ≤1.5 Warfarin (1mg orally, once daily) or low-dose aspirin (between 80mg and 100mg daily); 9. Arterial / venous thrombosis events, such as cerebrovascular accidents (including temporary ischemic attacks), deep vein thrombosis, and pulmonary embolism, occurring within 6 months before the first medication; 10. Severe or non-healing wounds, ulcers or fractures or abdominal fistulas, gastrointestinal perforations, abdominal abscesses, major medical history of open biopsy or significant trauma within 28 days prior to administration except for craniotomy and tumor removal 11. The researcher judges other situations that may affect the progress of the clinical study and the determination of the research results, and considers them unsuitable for inclusion.

12\. Pregnant or lactating women; 13. Have previously used other anti-angiogenic drugs or preparations.