Apatinib in the Treatment of Recurrent Atypical/malignant Meningioma in Adults

Inclusion Criteria:

1. Age ≥18 years old (at the time of enrollment), regardless of gender.

2. The pathological diagnosis of atypical/malignant meningioma was clear after biopsyor surgery.

3. The tumor recurrence is confirmed by MRI, that is, the diameter of the lesion on theenhanced MRI image is ≥1cm, and ≥2 slices (slice interval 5mm) are visible; or afteranother biopsy or surgery, the pathological diagnosis is atypical/malignantmeningioma.

4. Previous surgery and radiotherapy (including conventional radiotherapy orstereotactic radiosurgery treatment) are required. There are no restrictions onwhether to receive chemotherapy or the number of times of the above treatments

5. The time interval from the last radiotherapy is ≥4 weeks.

6. The time interval from the last chemotherapy is ≥4 weeks, and the patients havefully recovered from the acute toxicity of the last treatment.

7. The interval between the last biopsy or surgery is ≥2 weeks.

8. KPS score ≥50 points.

9. If the patient is on glucocorticoid therapy, the hormone dosage has stabilized ordecreased for at least 2 weeks before the baseline MRI.

10. The expected survival time is ≥12 weeks.

11. The main organ functions are normal, and there is no serious blood, heart, lung,liver, kidney dysfunction and immune deficiency diseases. The laboratory inspectionmeets the following requirements:

(1) Routine blood examination, which must be met (no blood transfusion within 14 days):

1. HGB≥100g/L;

2. WBC≥3.0×109/L; NEUT≥1.5×109/L;

3. PLT ≥100×109/L; (2) The biochemical inspection shall meet the following standards:

a. BIL≤1.5 times the upper limit of normal (ULN); b. ALT and AST≤2.0×ULN; c. Serum Cr≤1.5×ULN or endogenous creatinine clearance ≥50ml/min (Cockcroft-Gault formula); (3) Occult blood in stool (-); (4) Urine routine is normal, or urine protein <(++), or 24-hour urine protein <1.0 g; (5) Left ventricular ejection fraction (LVEF) ≥50%. 12. The coagulation function is normal, without active bleeding and thrombosis.

1. International standardized ratio INR≤1.5×ULN;

2. Partial thromboplastin time APTT≤1.5×ULN;

3. Prothrombin time PT≤1.5ULN. 13. Female patients of childbearing age must undergo anegative pregnancy test (serum or urine) within 7 days before enrollment, andvoluntarily use appropriate methods of contraception during the observation periodand within 8 weeks after the last administration of apatinib mesylate tablets ; Malepatients of childbearing age should agree to use appropriate methods ofcontraception during the observation period and within 8 weeks after the lastadministration of apatinib mesylate tablets.

4. Patients need to provide 25-30 pieces of tumor tissue slices after the lastbiopsy or surgery.

5. The patient has normal swallowing function and can swallow the tablet intact.

6. The patient voluntarily joined the study and signed an informed consent form (ICF).

7. The patient is expected to have good compliance and be able to follow up theefficacy and adverse reactions as required by the protocol.

Exclusion Criteria:

1. Past application of anti-tumor angiogenesis drugs;

2. Patients diagnosed with neurofibromatosis type 2 and other tumor syndromes;

3. People who are known to be allergic to any component of apatinib mesylate;

4. Antiepileptic drugs that induce liver enzymes are being used, unlessantiepileptic drugs that have been replaced with non-hepatic enzymes are atleast 2 weeks away from enrollment;

5. Patients with other malignant tumors, unless they have survived for 5 years andthe investigator believes that the risk of recurrence is low or patients withcarcinoma in situ;

6. Patients with hypertension who cannot be reduced to the normal range aftertreatment with antihypertensive drugs (systolic blood pressure ≤ 140 mmHg /diastolic blood pressure ≤ 90 mmHg);

7. Patients with coronary heart disease ≥2 grade, arrhythmia (including QTcprolongation in men>450 ms, women>470 ms) and cardiac insufficiency;

8. Urine routine test indicates urine protein ≥(++), or 24-hour urine protein ≥1.0g;

9. Abnormal coagulation function (INR>1.5 or prothrombin time (PT)>ULN+4 secondsor APTT>1.5×ULN), have bleeding tendency or are receiving thrombolytic oranticoagulant therapy;

10. There are many factors that affect the absorption of oral drugs, such asuncontrollable nausea and vomiting, chronic diarrhea and intestinalobstruction;

11. There is an infection that is difficult to control;

12. Those who had significant blood coughing up 2 months before enrollment, or hadblood volume of 2.5ml or more per day; had clinically significant bleedingsymptoms or had clear bleeding tendency within 3 months before enrollment, suchas Gastrointestinal bleeding, hemorrhagic gastric ulcer, gastrointestinalperforation, stool occult blood++ and above at baseline, intratumoral orintracranial hemorrhage, or vasculitis, etc.;

13. Arterial/venous thrombosis events that occurred within 6 months beforeenrollment, such as cerebrovascular accidents (including temporary ischemicattacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis andpulmonary embolism;

14. Pregnant or breast-feeding women; fertility patients who are unwilling orunable to take effective contraceptive measures;

15. Other situations that the researcher thinks are not suitable for inclusion.