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

This is an interventional treatment trial for Glioblastoma, Recurrent Read More

Inclusion Criteria:

1. Age ≥ 18 and ≤70;
2. Histopathologically-confirmed, supratentorial GBM or lower-grade gliomas (such as oligodendroglioma, astrocytoma, oligoastrocytoma, anaplastic astrocytoma, anaplastic oligodendroglioma or anaplastic oligoastrocytoma);
3. 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;
4. Received standard chemoradiotherapy and at least one cycle of chemotherapy after primary diagnosis;
5. The time intervals between the last radiotherapy and enrollment are at least 3 months;
6. 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);
7. Karnofsky Performance Status ≥ 60;
8. If the patient is on glucocorticoid therapy, hormone dosage should be stable or decreased at least 5 days before baseline MRI;
9. 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;
10. Estimated survival of at least 12 weeks;

11. Participants must have adequate organ function as defined by the following criteria (within 7 days before treatment):

    1. Hematology (No transfusion within 14 days):

       • Hemoglobin(HB)≥90g/L;

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

           • Platelet (PLT)≥80×109/L.

    2. 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；
    3. 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.
12. Both men and women at the gestational age must agree to take adequate contraceptive measures throughout the study period.
13. Participants volunteered to participate in the study and signed an informed consent form (ICF)

Exclusion Criteria:

1. MRI examination is not available (such as pacemaker, metal denture);
2. Receiving any other investigational agent.
3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to the drugs used in this study.
4. Patients who have received organ transplants.
5. Patients with HIV or Treponema pallidum infection.
6. Severe heart disease; ECG shows T wave inversion or elevation or ST segment specific changes.
7. Having factors that affect oral drug absorption, such as vomiting, diarrhea and intestinal obstruction
8. 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;
9. 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.;
10. Having bleeding disorder and are being treated with thrombolytic or anticoagulant drugs.
11. Other conditions considered inappropriate by the researcher for inclusion.