high-grade glioma
Conditions
Interventions
Trial group 1:Drug name: rHSV-1-APD1
Dosage: 1 × 10^7 PFU
Usage: Intraperitoneal injection of Ommaya
Trial group 2:Drug name: rHSV-1-APD1
Dosage: 1x10^8 PFU
Usage: Intraperitoneal injection of Ommaya
Trial group 3:Drug name: rHSV-1-APD1
Dosage: 4x10^8 PFU
Usage: Intraperitoneal injection of Ommaya
Sponsors
Beijing Tiantan Hospital Affiliated to Capital Medical University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Aged >=18 years, gender not limited; 2. Recurrence/progression or secondary high-grade glioma (WHO grade III-IV) after standard treatment or intolerance to standard treatment; 3. There is an Ommaya cyst catheter implanted in the tumor cavity; 4. KPS >= 60 points; 5. The expected survival time is >= 3 months; 6. Have sufficient organ functions: (1) ANC >= 1.5×10^9/L, PLT >= 90 ×10^9/L, Hb >= 90 g/L (no blood transfusion or hematopoietic stimulating factor treatment within 14 days); (2) TBIL <= 1.5×ULN, ALT<= 3×ULN, AST<= 3×ULN (For patients with liver metastasis or liver cancer, ALT <= 5×ULN, AST<= 5×ULN); (3) Cr <= 1.5×ULN; (4) APTT <= 1.5×ULN, INR or PT<= 1.5×ULN; 7. No steroid treatment was received within 5 days before enrollment, or the dosage of steroid treatment was stable (5mg/ day) or was in the process of dose reduction (needed to be reduced to 5mg/ day) within 5 days before the first administration; 8. Fertile subjects (both male and female) must agree to use medically approved contraceptive measures with their partners during the study period and for at least 90 days after the last medication use; Female subjects with fertility must have a negative blood pregnancy test within 7 days before enrollment. 9. Voluntarily participate in the test and sign a written informed consent form.
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria will not be included in this study: Disease 1. Have a history of any other malignant tumors within 5 years (except for effectively controlled basal cell carcinoma of the skin, carcinoma in situ of the cervix, and other malignant tumors that have been effectively controlled without treatment in the past 5 years); 2. Patients with brain tumors who have severe brain herniation or are at risk of brain herniation; 3. Active hemorrhage was found through cranial CT or MRI scans before enrollment; 4. Those who are unable to undergo cranial MRI examinations (such as those with pacemakers, those who cannot have metal dentures removed, or those allergic to MRI contrast agents, etc.); 5. Other patients with active extracranial malignant tumors that require concurrent treatment; 6. Where there is a passage between the tumor cavity and the ventricle after tumor resection; 7. Severely infected individuals who require systemic treatment with antiviral or antibacterial drugs; 8. Previous history of encephalitis, multiple sclerosis or other central nervous system infections; 9. In the period of recurrent herpes simplex virus infection and with corresponding clinical manifestations (such as cold sores, herpetic keratitis, herpetic dermatitis, genital herpes, etc.), or requiring anti-HSV treatment; 10. Active hepatitis B, positive for HBsAg and HBV DNA higher than the upper limit of normal values in the research center; Active hepatitis C, with positive antibodies and positive HCV RNA detection; 11. Uncontrollable pleural effusion, pericardial effusion or still requiring frequent aspiration of ascites; 12. Impaired cardiac function or clinically significant cardiovascular and cerebrovascular diseases, including but not limited to: a) There are severe cardiac rhythm or conduction abnormalities, such as severe uncontrolled arrhythmias requiring drug treatment, QTc intervals >= 480ms, etc. b) A history of myocardial infarction or bypass surgery, stent surgery, congestive heart failure (NYHA grade III-IV), or unstable angina pectoris within 6 months before the first administration; c) Left ventricular ejection fraction (LVEF) < 50%; 13. Other serious diseases that have not been effectively controlled, such as diabetes, liver diseases, hypertension, interstitial pneumonia, kidney failure, acute pancreatitis and autoimmune diseases, etc. Past medical history or concomitant treatment 14. Systemic chemotherapy (such as nitrosamuras and mitomycin C) was received within 4 weeks before the first use of the study drug or within 5 half-lives of the therapeutic drug (whichever is shorter). Any anti-tumor treatments such as radiotherapy and immunotherapy should be excluded if the time of the first study medication is less than 6 weeks from the last chemotherapy, targeted therapy (oral fluorouracil and small molecule targeted drugs should be excluded if the time from the first use of the study drug is less than 2 weeks or the 5 half-lives of the drug, whichever is longer), radiotherapy, and immunotherapy. Those who have used traditional Chinese medicine with anti-tumor indications within one week before the first use of the study drug or plan to undergo other anti-tumor treatments during the study period; 15. Those who have received other clinical research drugs within 4 weeks before the first use of the research drug or within 5 half-lives (whichever is shorter); 16. Immunomodulatory drugs, including but not limited to thymo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-limiting toxicity;Maximum tolerated dose;Adverse event; | — |
Secondary
| Measure | Time frame |
|---|---|
| rHSV-1-APD1 DNA;Cytokine;Lymphocyte classification;PD-1 antibody;Anti-drug antibody;HSV-1 neutralizing antibody;Objective response rate;Disease control rate;Progression free survival;Disease free survival;Overall survival;6-month disease-free survival;12-month disease-free survival;6-month progression-free survival;12-month progression-free survival;12 month survival ratio; | — |
Countries
China
Contacts
Public ContactLi Wenbin
Beijing Tiantan Hospital Affiliated to Capital Medical University
Outcome results
None listed