Study of Recombinant Human Endostatin Combined with Temozolomide and Irinotecan in Recurrent Gliomas

Inclusion criteria

• Age ≥ 18 and ≤70;
• Histopathologically-confirmed, supratentorial GBM or lower-grade gliomas (such as oligodendroglioma, astrocytoma, oligoastrocytoma, anaplastic astrocytoma, anaplastic oligodendroglioma or anaplastic oligoastrocytoma);
• Recurrence is pathologically confirmed by another biopsy or surgery, which should have been completed at least 2 weeks before enrollment, or confirmed by the MRI according to RANO criteria, at least one bi-dimensionally measurable contrast-enhancing target lesion, with one diameter at least 10 mm, visible on two or more axial slices 5mm apart;
• Received standard chemoradiotherapy and at least one cycle of chemotherapy after primary diagnosis;
• The time intervals between the last radiotherapy and enrollment are at least 3 months;
• The interval form the last chemotherapy to the study enrollment was at least one interval of chemotherapy with recover from the related toxic effects (except for hair loss and pigmentation);
• Karnofsky Performance Status ≥ 60;
• If the patient is on glucocorticoid therapy, hormone dosage should be stable or decreased at least 5 days before baseline MRI;
• If the patient is receiving enzyme-inducing antiepileptic drugs (EIAEDs), the drugs should be replaced with non-EIAEDs for at least 1 weeks away from enrollment;
• Estimated survival of at least 12 weeks;
• Participants must have adequate organ function as defined by the following criteria (within 7 days before treatment):

• Hematology (No transfusion within 14 days):

• Hemoglobin(HB)≥90g/L;

• Absolute neutrophil count (ANC)≥1.5×109/L;

• Platelet (PLT)≥80×109/L.
• Chemistry:

• Serum bilirubin ≤ 1.5×upper limit of normal (ULN)

• ALT and AST≤2.5ULN；

• Serum creatinine ≤1.5ULN or creatinine clearance rate(CCr)≥60ml/min；
• ECG: heart rate in the normal range (55-100beats/min), normal or slightly prolonged QT interval (QTc<480ms), normal or low T wave, normal or non-specific ST segment changes.
• Both men and women at the gestational age must agree to take adequate contraceptive measures throughout the study period.
• Participants volunteered to participate in the study and signed an informed consent form (ICF)

Exclusion criteria

• MRI examination is not available (such as pacemaker, metal denture);
• Receiving any other investigational agent.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the drugs used in this study.
• Patients who have received organ transplants.
• Patients with HIV or Treponema pallidum infection.
• Severe heart disease; ECG shows T wave inversion or elevation or ST segment specific changes.
• Having factors that affect oral drug absorption, such as vomiting, diarrhea and intestinal obstruction
• There were clinically significant bleeding symptoms or clear bleeding tendency in the first 3 months before enrollment, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, gastrointestinal perforation, baseline fecal occult blood ++ and above, intracranial or intracranial hemorrhage, or vasculitis;
• Arteriovenous thrombosis events occurred within 6 months before enrollment, such as cerebrovascular accidents (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc.;
• Having bleeding disorder and are being treated with thrombolytic or anticoagulant drugs.
• Other conditions considered inappropriate by the researcher for inclusion.