recurrent glioma with high-grade MGMT promoter
Conditions
Interventions
Study group (Teniposide combined with bevacizumab):None
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1.A. Age: 18 to 80 years old; 2.B. Underwent surgical resection at the Department of Neurosurgery of West China Hospital. Postoperative pathological diagnosis confirmed high-grade glioma (in accordance with the WHO 2021 standard), and postoperative recurrence was treated with teniposide combined with bevacizumab. 3.C. Tumor molecular detection confirmed that the MGMT promoter unmethylated; 4.D. The enhanced magnetic resonance imaging results meet the definition of recurrence/progression in the RANO2.0 criteria, that is, when the dose of corticosteroid hormones is stable or increased, the sum of the products of the vertical diameters of the lesions increases by 25%, or the volume increases by 40%, or new measurable lesions appear; 5.E. KPS scores 60 points or above; 6.F. Expected survival period no less than 6 months; 7.G. Adequate bone marrow hematopoietic function: absolute neutrophil count >1.5*10^9L, platelet count >90*10^9/L, hemoglobin >90 G /L; 8.H. The international normalized ratio is <= 1 times the upper limit of the normal value, and there is no bleeding tendency (such as skin purpura, epistaxis, digestive tract bleeding, vaginal bleeding, etc.); 9.I. Female subjects who are fertile or male subjects whose partners are fertile must adopt highly effective contraceptive measures starting 7 days before the first administration until 24 weeks after the last administration. Female subjects with fertility must have a negative serum pregnancy test within 7 days before the first administration. Female patients who have no possibility of having children should have experienced natural amenorrhea for at least 12 months or have undergone bilateral oophorectomy, hysterectomy or tubal ligation 6 weeks before the screening period.
Exclusion criteria
Exclusion criteria: 1.A. The possibility of false progression in enhanced magnetic resonance imaging is relatively high; 2.B. Previous use of anti-angiogenic therapy or other experimental therapeutic drugs:; 3.C. Use of low-molecular-weight heparin and warfarin within 35 days before enrollment:; 4.D. Had arterial or venous thrombosis occurred (such as cerebral infarction, myocardial infarction, lower extremity venous thrombosis, lower extremity arterial embolism, pulmonary embolism, etc.) within 6 months before enrollment; 5.E. Subjects who were treated with enzyme-induced antiepileptic drugs (such as carbamizine, primidone, phenobarbital carbamazepine, oxcarbazepine, phenytoin sodium) or whose grand mal seizures were not effectively controlled by the drugs within 14 days before enrollment:; 6.F. Subjects with severely impaired liver or kidney function: Alanine aminotransferase or aspartate aminotransferase >2.5 times the upper limit of the normal value, total bilirubin >1.5 times the upper limit of the normal value; Serum creatinine >1.5 times the upper limit of the normal value, or the creatinine clearance rate calculated according to the Cockcroft-Gault formula = Grade I], uncontrolled hypertension [diastolic blood pressure >100 mmHg]; Systolic blood pressure >150mmmHg, uncontrolled hyperglycemia [fasting glycated hemoglobin >8%], arrhythmia or prolonged QTc interval (>450ms in men; >470ms in women); There is a risk of other factors causing tortonal ventricular tachycardia [TdP] (such as heart failure, hypokalemic signs, familial long QT syndrome) or the combined use of drugs that may lead to prolonged QT/QTC intervals; 10.J. Patients with malabsorption syndrome, a disease that significantly affects gastrointestinal function, or those who have had their stomach or small intestine removed. Patients with ulcerative colitis, inflammatory bowel disease, and incomplete or complete small intestinal obstruction; 11.K. Patients with chronic HepatitisB (HepatitisB, with HBV DNA levels higher than the upper limit of normal in subjects with "big three positive" or "small three positive" of hepatitis B), hepatitis C, etc. Combined human immunodeficiency virus (HIV) infection:; 12.L. During pregnancy or lactation; 13.M. Subjects who were unable to take adequate contraceptive measures during the study period and within 6 months after the end of the study; 14.N. Those who are known to have an active autoimmune disease or a history of autoimmune disease and require systemic steroids, with dexamethasone >5mg daily for 2 weeks before randomization, or equivalent doses of other corticosteroid hormones or immunosuppressants (such as cyclophosphamide, azathioprine, methotrexate, thalidomide and TNF-a) Antagonists, etc. (Note: Patients who have inhaled bronchodilators or steroids locally should not be excluded. Patients with hypothyroidism who need hormone replacement therapy and have stable disease should not be excluded either.); 15.O. Suffering from a known mental illness that may affect trial compliance:; 16.P. R
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| objective remission rate;Incidence of adverse reactions;clinical benefit rate;progression free survival;overall survival; | — |
Countries
China
Contacts
Public ContactYanhui Liu
Westchina hospital of Sichuan University
Outcome results
None listed