Advanced primary hepatocellular carcinoma
Conditions
Interventions
2 dose groups, 3 cases in each group:Drug therapy
Sponsors
The Third People's Hospital of Shenzhen
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Voluntarily participate in clinical studies; fully understand, be aware of, and sign the ICF; be willing to follow and have the ability to complete all trial procedures; 2. Be between the ages of 18 and 80 (inclusive) at the time of signing the ICF; 3. Patients with advanced primary hepatocellular carcinoma who are clinically judged to be unresectable and who are ineffective (primary resistance) or who are resistant to primary hepatocellular carcinoma after initial resistance (secondary resistance) are clinically judged to be unresectable and who are ineffective (primary resistance) or who are resistant after standard therapy > is initially effective (secondary resistance); 4. At least one lesion that cannot be surgically resected and can be injected directly or by imaging-guided real-time intratumor injection, imaging examination of three-phase CT scan or dynamic control enhanced MRI image shows: at least one lesion, 10 mm= 12 weeks; 7. Full organ function: hematologic system ANC >= 1.5*10^9 /L, platelet >= 60*10^9 /L, hemoglobin >= 90 g/L; Liver function Total bilirubin = 2.8 g/dL; renal functional creatinine = 50 ml/min (calculated according to the Cockcroft-Gault formula, Ccr is calculated only at creatinine > 1.5*ULN; coagulation function APTT=50 years, if they have stopped menstruation for 12 months or more after stopping all exogenous hormone therapy, or if radiotherapy induces oophorectomy and the last menstrual period occurred before >1 year, Either chemotherapy induces menopause and the last menstrual period > 1 year, or has undergone surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy), it may be considered a postmenopausal woman; 11. Eligible subjects with fertility (both male and female) must agree to use effective birth control measures (hormone or barrier or abstinence) with their partners during the trial and for at least 90 days after the last dose.
Exclusion criteria
Exclusion criteria: 1. Have received any systemic anti-tumor therapy, including chemotherapy, biological therapy, hormones, radiotherapy, etc., within 2 weeks before the first use of the research drug, and have received any local treatment or surgery for the target lesion within 4 weeks before the first use of the research drug, including ethanol injection, radiofrequency ablation, transarterial chemotherapy embolization, intrahepatic intraarterial chemotherapy, etc., except for the following: (1) Nitrosourea or mitomycin C within 6 weeks before the first use of the study drug; (2) Oral fluorouracils and small molecule targeted drugs are 2 weeks before the first use of the study drug or 5 half-lives of the drug (whichever is longer); (3) Palliative radiotherapy for non-central nervous system diseases is allowed an elution period of 2 weeks, which must be recovered from radiotherapy-related toxicity; 2. Received systemic glucocorticoids (prednisone > 10 mg/day or equivalent doses of the same drug) or other immunosuppressant therapy within 14 days prior to the first use of the study drug; Excludes treatment with topical, ocular, intraarticular, intranasal, and inhaled glucocorticoids and short-term prophylactic therapy (e.g., prevention of contrast allergies); 3. Use of immunomodulatory drugs in the 14 days prior to the first use of the study drug, including but not limited to thymus peptides, interleukin-2, interferons, etc; 4. Live attenuated vaccines were used within 4 weeks prior to the first use of the study drug, including but not limited to: measles, mumps, rubella, chickenpox/herpes zoster, yellow fever, rabies, BCG and typhoid vaccines. Seasonal influenza vaccines for injection are inactivated viral vaccines and are therefore allowed, while intranasal influenza vaccines are attenuated or vaccines and are not allowed; 5. Have previously been treated with oncolytic viruses or other gene drugs; 6. Received treatment with other unlisted clinical study drugs within 4 weeks prior to the first use of the study drug; 7. Enroll in another clinical study at the same time, except during the observational (non-interventional) clinical study or the follow-up phase of an interventional study; 8. Have had major organ surgery (excluding puncture biopsy) or have had significant trauma within 4 weeks prior to the first use of the study drug, or require elective surgery during the trial; 9. The adverse reactions of previous anti-tumor therapy have not yet returned to NCI-CTCAE V5.0 rating <= 1 (except for toxicity that researchers judge there is no safety risk such as hair loss); 10. Central nervous system metastases or meningeal metastases with clinical symptoms, or other evidence that the patient's central nervous system metastases or meningeal metastases have not been controlled, are judged by researchers to be unsuitable for enrollment, and patients with clinical symptoms suspected of brain or meningeal diseases need CT/MRI to be excluded; 11. Have a history of leptomeningal disease; 12. There is evidence of uncontrolled severe comorbidities that may affect patient adherence to the study protocol, including severe liver disease (e.g., severe esophageal varicose veins requiring intervention, hepatic encephalopathy, or superior vena cava syndrome); 13. Have a history of severe cardiovascular disease, including but not limited to: (1) Severe heart rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, sec
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Frequency and properties of DLT (Dose-limiting toxicity);Adverse Events;Serious Adverse Event;Adverse Event of Special Interest;Physical examination;Vital sign;Laboratory examination; | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Response Rate, ORR;Disease Control Rate, DCR;Improvement of AFP after administration; | — |
Countries
China
Contacts
Public ContactXiaohua Tan
The Third People's Hospital of Shenzhen
Outcome results
None listed