HCC
Conditions
Interventions
treatment group:Oncolytic Immunotherapy ONCORINE combined with pd-1 antibody.
Sponsors
Fudan University Shanghai Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: (1) Males and females, ages 18 or older. (2) Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. See Appendix 1 for ECOG Performance Status scale. (3) Histologic confirmation of hepatocellular carcinoma, or subjects with a radiologic diagnosis of HCC and chould be diagnosised as HCC with Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2017 Edition). (4) Subjects with advanced hepatocellular carcinoma i) disease not eligible for curative surgical and/or locoregional therapies, or ii) progressive disease after surgical and/or locoregional therapies failed or not tolerant from at least one or more prior systemic therapy for hepatocellular carcinoma. a) chemotherapy includes FOLFOX or any other platinum-based chemotherapy. b) >=2 cycles chemotherapy. (5) At least one RECIST 1.1 measurable untreated lesion. All subjects must have at least one previously untreated, unidimensionally measurable lesion by contrast-enhanced spiral computed tomography (CT) >= 10 mm or contrast enhanced dynamic magnetic resonance imaging (MRI) scan >= 10 mm (malignant lymph nodes must be >= 15 mm on short axis). i) The lesion can be accurately measured uni-dimensionally according to RECIST 1.1; ii) The lesion can be previously treated with surgery, radiotherapy, and/or locoregional therapy (eg: radiofrequency ablation [RFA], percutaneous ethanol [PEI] or acetic acid injection [PAI], cryoablation, high-intensity focused ultrasound [HIFU], transarterial chemoembolization [TACE], transarterial embolization [TAI], etc.) ,and has the prof of progression according to RECIST 1.1 criteria. (6) At least one untreated lesion for local injection of ONCORINE and biopsy, and can be evaluated as a non-target lesion. (7) Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care. Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study. (8) Screening laboratory values must meet the following criteria, without continuous supportive treatment such as growth factor administration, blood transfusion, coagulation factors and/or platelet transfusion, or albumin transfusion, and should be obtained within 14 days prior to randomization). i) Adequate hematologic function: WBC >= 2000/µL; Neutrophils >= 1500/µL; Platelets >=90 x 10^9/L; Hemoglobin >=8.5 g/dL. ii) Prothrombin time (PT)-international normalized ratio (INR) = 2.8 g/dL; total bilirubin 40 mL/min (Cockcroft-Gault formula). (9) Adequate cardiac function with a left ventricular ejection fraction (LVEF) > 50% as measured by 2-D echocardiography.
Exclusion criteria
Exclusion criteria: (1) Prior ONCORINE and/or immune therapy (eg. with anti-CTLA-4 or anti-PD-1/PD-L1 treatment). (2) Radiotherapy within 2 weeks prior to start of study drug. Palliative radiotherapy for symptomatic control is acceptable (if completed at least 2 weeks prior to study drug administration) and no additional radiotherapy for the same lesion is planned. (3) Major surgical procedure, open biopsy, or significant traumatic injury within 2 weeks prior to start of investigational product administration or those who receive minor surgical procedures (eg, core biopsy or fine needle aspiration) within 1 week prior to the start of investigational product. (4) Hepatic encephalopathy. Active brain metastases or leptomeningeal metastases. (5) Evidence of portal hypertension with bleeding esophageal or gastric varices within the past 6 months. (6) Subjects who are unable to swallow tablets, requiring intravenous alimentation, malabsorption syndrome, or any conditions affecting gastrointestinal absorption; or active peptic ulcer disease. (7) Subjects with any active, known, or suspected autoimmune disease, with the following exceptions: i) Subjects with vitiligo, type 1 diabetes mellitus, resolved childhood asthma or atopy are permitted to enroll. ii) Subjects with suspected autoimmune thyroid disorders may be enrolled if they are currently euthyroid or with residual hypothyroidism requiring only hormone replacement. iii) Subjects with psoriasis requiring systemic therapy must be excluded from enrollment. (8) Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast. (9) WOCBP who are pregnant or breastfeeding. (10) Prior EGFR and ALK inhibitors within half a year (the overall administration >= one month). (11) Any other adverse event unrecovered >= CTCAE Grade 2 within 2 weeks except for fatigue, anemia, and alopecia. (12) Infections: i) Active co-infection with: (a) Both hepatitis B and C as evidenced by detectable HBV surface antigen or HBV DNA and HCV RNA, or (b) Hepatitis D infection in subjects with hepatitis B. ii) Subjects with a history of coinfection with both hepatitis B and C,including (a) HBV DNA positive or HBV surface antigen positive subjects with detectable HCV antibody, or (b) HCV RNA positive subjects with resolved HBV infection as evidenced by detectable HBV surface antibody, detectable HBV core antibody, undetectable HBV DNA, and undetectable HBV surface antigen. iii) Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). iv) Active bacterial or fungal infections requiring systemic treatment within 7 days prior to screening (13) Prior liver transplant. (14) Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg/day prednisone equivalent) or other immunosuppressive medications within 14 days of study administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg/day prednisone equivalents are permitted in the absence of active autoimmmune disease. (15) Interstitial lung disease that is symptomatic or may interfere with the detection and management of suspected drug-related pulmonary toxicity. (16) History of active cardiac disease as evidenced by the following: i) Uncontroll
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ORR;6-month OS%; | — |
Secondary
| Measure | Time frame |
|---|---|
| DoR;PFS;OS;DCR;safety (ctcAE 5.0); | — |
Countries
China
Contacts
Public ContactMeng Zhiqiang
Fudan University Shanghai Cancer Center
Outcome results
None listed