Primary Central Nervous System Tumor/Solid Tumor Brain Metastases
Conditions
Interventions
Trial group 1:Drug name: rHSV-1-APD1
Dose: 1×10^7 PFU for the first dose, followed by 4×10^7 PFU
Usage: intravenous infusion
Trial group 2:Drug name: rHSV-1-APD1
Dose: 1×10^7 PFU for the first dose, followed by 1×10^8 PFU
Usage: intravenous infusion
Trial group 3:Drug name: rHSV-1-APD1
Dose: 1×10^7 PFU for the first dose, followed by 4×10^8 PFU
Usage: intravenous infusion
Trial group 4:Drug name: rHSV-1-APD1
Dose: 1×10^8 PFU
Usage: intravenous infusion
Trial group 5:Drug name: rHSV-1-APD1
Dose: 4×10^8 PFU
Usage: intravenous infusion
Sponsors
Beijing tiantan hospital, capital medical university
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Aged >=18 years, both sexes; 2. Recurrent/progressive primary central nervous system tumors or solid tumors brain metastases that have been treated with standard therapy or cannot tolerate standard therapy, or are not suitable for surgical resection or have postoperative residual lesions; 3. At least one central nervous system measurable lesion; 4. KPS >= 60; 5. Estimated survival time >= 3 months; 6. Adequate organ function: 7. Fertile subjects (male and female) must consent to use medically approved contraception with their partner during the study and for at least 90 days after the last dose; Fertile female subjects must have a negative blood pregnancy test within 7 days prior to enrollment; 8. Voluntarily sign written informed consent.
Exclusion criteria
Exclusion criteria: 1. History of any other malignancies within 5 years (other than basal cell carcinoma of the skin, carcinoma in situ of the cervix, and other malignancies that have been effectively controlled without treatment in the past 5 years and double primary tumors that the investigator believes could benefit from the clinical trial); 2. Patients with brain tumors with severe cerebral hernia or risk of cerebral hernia; 3. Brain CT or MRI scan showed active bleeding before enrollment; 4. Patients who are unable to undergo brain MRI examination (such as pacemakers installed, metal dentures not advisable, allergic to MRI contrast agents, etc.); 5. Severely infected people who need systemic treatment with antiviral or antimicrobial drugs; 6. In the stage of recurrent herpes simplex virus infection, and there are corresponding clinical manifestations (such as oral herpes, herpetic keratitis, herpetic dermatitis, genital herpes, etc.), or need anti-HSV treatment; 7. Active hepatitis B, HBsAg positive and HBV DNA higher than the upper limit of normal in the study center; Active hepatitis C, positive for antibodies and positive for HCV RNA; 8. Uncontrolled pleural effusion, pericardial effusion, or frequent ascites extraction; 9. Impaired cardiac function or clinically significant cardiovascular and cerebrovascular diseases, including but not limited to: 10. Patients with active or past autoimmune diseases with the possibility of recurrence (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), except clinically stable autoimmune thyroid disease; 11. Other serious diseases that are not effectively controlled, such as interstitial pneumonia, kidney failure, acute pancreatitis, etc.; 12. Systemic chemotherapy within 4 weeks prior to initial use of the study drug (nitrosourea and mitomycin C within the first 6 weeks; Or have used oral fluorouracil chemotherapy), radiotherapy, immunotherapy or any other anti-tumor therapy in the previous 2 weeks, or plan to undergo other systemic anti-tumor therapy during the study period; Extension stage: The last radiotherapy for brain lesions was at least 90 days from baseline. The last bevacizumab was at least 28 days from baseline. If the baseline MRI is less than 90 days from the last radiotherapy to the brain lesion, it may still be included if one or more of the following criteria are met: (1) The investigator-identified progressive tumor is outside the original radiotherapy target, or (2) The progressive lesion in the original radiotherapy target is confirmed as a tumor by biopsy or excision histologically, or (3) Lesion enlargement at baseline confirmed by nuclear medicine imaging, magnetic resonance spectroscopy, or magnetic resonance perfusion imaging to be consistent with true progressive disease, rather than spurious progression or radionecrosis. 13. Use of small molecule targeted anti-tumor drugs or use of traditional Chinese medicine with anti-tumor indications within 2 weeks before the first use of the investigational drug; 14. Patients who have received other investigational drugs within 4 weeks prior to the first use of investigational drugs; 15. Received systemic steroid ( > 5mg/ day dexamethasone or equivalent corticosteroid hormone) or other immunosuppressive therapy within 14 days prior to the first use of the study drug; The following are excluded: treatment with local, ocular, intraarticular, intranasal, and inhaled corticosteroids; Short-term use of glucocorticoids for preve
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-limiting toxicity;Adverse event; | — |
Secondary
| Measure | Time frame |
|---|---|
| rHSV-1-APD1 DNA;Cytokine;PD-1 antibody;Anti-drug antibody;HSV-1 neutralizing antibody;Objective response rate;Survival ratio at month 12th;Seizure control rate; | — |
Countries
China
Contacts
Public ContactWenbin Li
IRB of Beijing Tiantan Hospital Affiliated to Capital Medical University
Outcome results
None listed