Advanced hepatocellular carcinoma
Conditions
Interventions
Trial group 1:Drug name: rHSV-1-APD1
Dose: 4×10^8 PFU
Usage: intravenous infusion,It was administered 5 times per cycle, D1~D5
Trial group 2:Drug name: rHSV-1-APD1
Dose: 1×10^9 PFU
Usage: intravenous infusion,It was administered 5 times per cycle, D1~D5
Trial group 3:Drug name: rHSV-1-APD1
Usage: D1, D2, D3 intravenous infusion (dose 4×10^8 PFU)
D5, D7 hepatic artery perfusion (dose 1×10^8 PFU)
Trial group 4:Drug name: rHSV-1-APD1
Usage: D1, D2, D3 intravenous infusion (dose 4×10^8 PFU)
D5, D7 hepatic artery perfusion (dose 4×10^8 PFU)
Trial group 5:Drug name: rHSV-1-APD1
Usage: D1, D2, D3 intravenous infusion (dose 4×10^8 PFU)
D5, D7 hepatic artery perfusion (dose 1×10^9 PFU)
Sponsors
The Second Affiliated Hospital of Zhejiang University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Age >=18 years old, gender unlimited; 2. HCC patients diagnosed with primary hepatocellular carcinoma (HCC) by pathology (histology and/or cytology) or by imaging diagnosis (e.g., dynamic enhanced CT or dynamic enhanced MRI); 3. HCC patients who have failed standard therapy (including at least immunotherapy or targeted therapy) or are intolerant to standard therapy, and are not suitable for surgical resection or cannot be completely surgically removed; 4. The presence of at least one evaluable lesion confirmed by the investigator (according to RECIST v1.1 criteria); 5. Only participants in Cohort 2 who were identified by the investigator as having at least one measurable intrahepatic tumor lesion that could be treated with hepatic arterial perfusion (meeting RECIST v1.1 criteria); 6. ECOG physical strength score 0-1; 7. Estimated survival time >=3 months; 8. Adequate organ function: a) a) WBC>=3.0×109/L, ANC>=1.5×10^9/L, PLT>= 75×10^9/L, Hb>=90 g/L (no blood transfusion or hematopoietic stimulating factor treatment within 14 days); b) ALT= 30 g/L; e) Cr= 50 ml/min; f) APTT<=1.5×ULN, INR or PT<=1.5×ULN (when receiving anticoagulant therapy, PT or APTT must be within the therapeutic range of anticoagulant use); 9. Child-Pugh Grade A or better Child-Pugh grade B (<= 7 points); 10. Fertile subjects must consent to adequate contraceptive use for 3 months (for men) or 6 months (for women) from screening until the end of the last study drug administration; Fertile female subjects must have a negative pregnancy test prior to enrollment; 11. Volunteer and sign a written informed consent.
Exclusion criteria
Exclusion criteria: 1. History of any other malignancies within 3 years (except for basal cell carcinoma of the skin, carcinoma in situ of the cervix and other malignancies that have been effectively controlled without treatment within the past 3 years); 2. Patients with clinical symptoms of central nervous system metastasis or meningeal metastasis, or other evidence that the central nervous system metastasis or meningeal metastasis has not been controlled, and the investigators judged that they were not suitable for inclusion; 3. 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; 4. Patients with severe infections that cannot be effectively controlled or who have taken intravenous antibiotics in the week prior to the first study treatment; 5. There is evidence of bleeding tendency or severe clotting disorder, or is receiving thrombolytic therapy (except conventional low-dose single-drug anticoagulant or antiplatelet therapy); 6. Active hepatitis B, HBsAg positive and HBV DNA >= 1000copies/ml or 2000IU/ml (if HBV-DNA >= 1000copies/ml or 2000IU/ml, antiviral therapy should be performed first, Enter the study until HBV-DNA drops below 1000copies/ml or 2000IU/ml, and continue to take antiviral drugs and monitor liver function and HBV markers); Active hepatitis C, positive for antibodies and positive for HCV RNA; 7. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage; 8. Impaired cardiac function or clinically significant cardiovascular and cerebrovascular diseases, including but not limited to: a) Have severe cardiac rhythm or conduction abnormalities, such as severe uncontrolled arrhythmias requiring medical treatment, QTc interval >=480ms, etc.; b) A history of myocardial infarction or bypass surgery, stent surgery, congestive heart failure, or unstable angina pectoris within 6 months prior to initial administration; c) New York Heart Association (NYHA) Heart function Grade > II or left ventricular ejection fraction (LVEF) 20mg/ day or equivalent dose of
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse event;Dose-limiting toxicity; | — |
Secondary
| Measure | Time frame |
|---|---|
| rHSV-1-APD1 copy number;Cytokine;Anti-drug antibody;HSV-1 neutralizing antibody;Objective response rate;Disease control rate;Progression free survival;6 months survival rate;12 months survival rate;Time to disease progression;Duration of remission; | — |
Countries
China
Contacts
Public ContactJiaqi Chen
The Second Affiliated Hospital of Zhejiang University School of Medicine
Outcome results
None listed