Recurrent high-grade glioma (CNSWHO 3/4)
Conditions
Interventions
Test group:Teniposide combined with temozolomide
Sponsors
West China Hospital, Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: Subjects enrolled must meet all of the following criteria at the same time: 1. age = 18 years, gender is not limited; 2. subjects with histopathologically or cytologically confirmed recurrent high-grade gliomas (based on the 2021 WHO Classification of Tumors of the Central Nervous System criteria, and CNSWHO grade 3 or 4, assessed by postoperative pathology or imaging confirmation of recurrence); 3. presence of at least 1 evaluable lesion according to RANO criteria; 4. toxic response to prior antitumor therapy must have recovered to CTCAE V5.0 Grade 1 or less (except alopecia); 5. if corticosteroids are used, the dose must have been stable for at least 3 days prior to determination of baseline imaging(Dexamethasone is considered dose stable at a total daily dose of =5 mg, other corticosteroids are converted to equivalent doses to dexamethasone); 6. Expected survival time =3 months; 7. Kahlil Functional Status Score (KPS) score =60 at baseline or Eastern Cooperative Oncology Group (ECOG PS) score of 0-1; 8. Post-operative radiotherapy, with an interval of not less than 3 months between the last radiotherapy treatment and entry into the cohort; 9. Not less than 4 weeks between the last chemotherapy; 10. Good hematopoietic function (total white blood cell count = 3.5×10^9 /L, absolute lymphocyte count = 0.8×10^9/L, absolute neutrophil count = 1.5×10^9/L, platelet count = 100×10^9/L, hemoglobin = 90g/L); 11. Good liver function (Bilirubin level = 1.5 times the upper limit of normal (ULN); Aspartate transaminase (AST) and alanine aminotransferase ALT level = 2.5 times ULN); 12. Good renal function (serum creatinine = 1.5 times the ULN or calculated creatinine clearance = 60 ml/min (Cockcroft-Gault formula), urinary routine examination of urinary protein is less than 2 +, or the quantitative amount of urinary protein < 1g in 24 hours); 13. Good coagulation function, defined as International Normalized Ratio (INR) or Prothrombin Time (PT) = 1.5 times the ULN, or, if the subject is receiving anticoagulation, as long as the PT is within the range of the anticoagulant intended to be used; 14. Absence of serious organic cardiac disease, as well as cardiac arrhythmia and immunodeficiency diseases; 15. Women of childbearing age (15-49 years old) must have had a negative pregnancy study within 7 days prior to the start of treatment; male and female patients of childbearing potential must agree to use effective contraception to ensure that they do not become pregnant during the study and for 3 months after discontinuation of treatment; 16. The patient voluntarily participates in the study and signs a written informed consent form, and is able to comply with the study protocol for treatment, visits, and other study procedures.
Exclusion criteria
Exclusion criteria: Subjects will not be enrolled if they meet any of the following criteria: 1. Antibody treatment less than 6 weeks; discontinuation of participation in a drug clinical trial less than 4 weeks; 2. Systemic immunosuppressant therapy (including, but not limited to, a daily prednisone dose of >30 mg, or an equivalent amount of corticosteroid hormone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and TNF-a antagonists) within 2 weeks prior to the initiation of study treatment; 3. Major surgery within 4 weeks prior to the first dose; bone marrow biopsy, open biopsy, or intracranial biopsy within 7 days prior to screening; 4. Inability to undergo enhanced MRI; 5. Need to receive a live viral vaccine during the period of administration; 6. Previous or concurrent other malignancies, except squamous cell carcinoma of the skin, basal cell carcinoma of the skin, cervical carcinoma in situ, thyroid carcinoma, or breast carcinoma cured for more than 5 years; 7. Baseline MRI suggestive of recent risk of cerebral hemorrhage or cerebral hernia; 8. Unremedied toxic reactions, excluding alopecia, resulting from any prior therapy above CTCAE (5.0) = Grade 3; 9. Inability to take medication or swallow; 10. Patients with any severe and/or uncontrolled disease, including: (1) Uncontrolled blood pressure (systolic blood pressure = 150 mmol/L) despite use of 1 antihypertensive drug; Patients with previous hypertensive encephalopathy; (2) Significant cardiovascular impairment including, but not limited to, = grade II cardiac insufficiency (New York Heart Association (NYHA) classification), unstable angina, myocardial infarction, ischemic cardiomyopathy, or stroke in the 6 months prior to the first dose of medication; (3) Grade 1 or greater sinus bradycardia (CTCAE 5.0); or second-degree or greater atrioventricular block, or sinus arrest (except where a pacemaker has been fitted); arrhythmias (including QTC =470ms); and those requiring concomitant use of medications known to prolong the QTc interval, including antiarrhythmic therapy; (4) Intracranial abscess within 6 months; (5) Active or uncontrolled serious infection (= CTCAE grade 2 infection); (6) Patients with cirrhosis, decompensated liver disease, active hepatitis, or chronic hepatitis; (7) Renal failure requiring hemodialysis or peritoneal dialysis; (8) History of immunodeficiency, including HIV-positive or other acquired or congenital immunodeficiency diseases, or history of organ transplantation; (9) Patients with diabetes mellitus with poor glycemic control (fasting blood glucose (FBG) > 10 mmol/L); Patients with routine urinalysis suggestive of urinary protein =++ and confirmed 24-hour urine protein quantification >1.0 g; 11. Patients with any signs or history of hemorrhagic constitution, regardless of severity; patients with any hemorrhagic or bleeding event unrelated to craniofacial surgery =CTCAE grade 2, the presence of unhealed wounds, ulcers, or fractures within 4 weeks prior to enrollment; 12. Patients with a 6 month Those who have had an arterial/venous thrombotic event, such as cerebrovascular accident (including temporary ischemic attack), deep vein thrombosis, and pulmonary embolism; 13. Those who have a history of psychotropic substance abuse and are unable to quit or have a psychiatric disorder; 14. Those who, in the judgment of the investigator, have a concomitant medical condition that would seriously jeopardize the patient's safety or interfere with
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety;6-Month Progression-free Survival Rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective Response Rate;Disease Control Rate;Progression-free Survival;Overall Survival; | — |
Countries
China
Contacts
Public ContactFeng Wang
West China Hospital, Sichuan University
Outcome results
None listed