Carcinoma, Hepatocellular
Conditions
Keywords
Hepatocellular carcinoma, Polyinosinic-polycytidylic acid, PD-1 mAb
Brief summary
When multi-kinase inhibitors based therapies (sorafenib and regorafenib) are limited in late-stage liver cancer patients, there is no alternative options. PD-1 blockade has became a promising immunotherapeutic strategy in many cancers. While it showed limited efficacy in liver cancer. Polyinosinic-polycytidylic acid (PolyIC) has been widely studied as a new anti-tumor drug and recent study showed that polyIC and PD-L1 mAb has a quite synergetic effect on the hepatocellular carcinoma (HCC). This study is aimed to evaluate the safety and efficacy of the combination of PolyIC and PD-1 mAb in unresectable late-stage HCC patients.
Detailed description
Nowadays, primary liver cancer, especially hepatocellular carcinoma (HCC) has become the second leading cause of cancer-related death. Unfortunately, the therapeutic strategies are still limited for HCC. For HCC patients at advanced stage, up to now, sorafenib and regorafenib are applied for palliative therapy to prolong the patients' life. PD-1 blockade has became a promising immunotherapeutic strategy in many cancers. While it showed limited efficacy in liver cancer. Polyinosinic-polycytidylic acid (PolyIC) has been widely studied as a new anti-tumor drug and recent study showed that polyIC and PD-L1 mAb has a quite synergetic effect on the treatment of HCC. This study is aimed to evaluate the safety and efficacy of the combination of PolyIC and PD-1 mAb in unresectable late-stage HCC patients.
Interventions
DRUGPD-1 mAb
Intravenous infusion of PD-1 mAb, 200mg, once a time, every three weeks.
DRUGPolyIC
Intramuscular injection of polyIC, 2mg, every other day, for three weeks.
Sponsors
Second Affiliated Hospital, School of Medicine, Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Hepatocellular carcinoma with imaging diagnosis, in barcelona stage C, or stage B but resistant/recurrent to prior local treatment (e.g., TACE). 2. Eastern cooperative oncology group physical fitness score: 0-2. 3. Predicted survival time≥3 months. 4. Liver function of Child-Pugh A-B, no hepatic encephalopathy or physical examined ascites. 5. Routine blood tests were in accordance with the following criteria: White blood cell (WBC)≥2.0x10\^9/L, Neutrophil≥1.0x10\^9/L, platelet (PLT)≥50x10\^9/L, hemoglobin (HB)≥80 g/dL, creatinine≤1.5xULN (upper limit of normal value), Alanine transaminase (ALT) and aspartate aminotransferase (AST)≤5xULN, total bilirubin (TB)≤51.3umol/L, international normalized ratio (INR) or prothrombin time (PT)≤1.7xULN, activated partial thromboplastin time (APTT)≤1.5xULN, serum albumin≥28g/L 6. Patients will be informed consent, and understand and are willing to cooperate with the trial and sign related documents.
Exclusion criteria
1. Has a history of malignant tumor in last 2 years, except basal and skin squamous cell carcinoma, cervical carcinoma in situ, papillary thyroid carcinoma, superficial bladder cancer and carcinoma in situ of breast. 2. Received the treatment of polyIC or immune checkpoint inhibitors (e.g., PD-1/PD-L1 mAb or CTLA-4 mAb) in last 2 years. 3. Received the therapies of multi-kinase inhibitors (e.g., sorafenib, regorafenib), systemic chemotherapy, local therapy (e.g., TACE, radiotherapy), vaccination, immunomodulating therapy （e.g., interleukins, thymosin） or any other clinical trial in last 4 weeks. 4. Received any corticosterone or immunosuppressive drug in last 2 weeks. 5. Toxicity induced by previous anti-tumor therapies has not returned to the status of baseline or stability. 6. HIV positive (including previous anti-retroviral therapy), active HCV infection or active syphilis. 7. Any severe liver disease (e.g., severe liver cirrhosis, severe liver adenoma) 8. Any active or recurrent autoimmune disease. 9. Any interstitial pneumonia, non-infectious pneumonia, or uncontrolled systemic disease (e.g., uncontrolled hypertension or diabetes). 10. Severe cardiovascular risk factors. 11. Has a history of allogeneic stem cell transplantation or organ transplantation. 12. Imaging confirmed brain or meninges metastases. 13. Has the plan of pregnancy, or lactation. 14. Any kind of psychiatric disease or laboratory test abnormality that may result in the subject's failure to fully comply with the laboratory protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Up to approximately 5 years | Percentage of patients whose cancer shrinks or disappears after treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) | Up to approximately 5 years | The percentage of people does not get worse for a period of time after diagnosis |
| Overall survival (OS) | Up to approximately 5 years | The percentage of people still alive for a given period of time after diagnosis |
| Disease control rate (DCR) | Up to approximately 5 years | Percentage of patients whose cancer doesn't progress after treatment |
| Percentage of participants with a better life quality | Up to approximately 5 years | The percentage of participants with a better life quality after treatment, assessed by the questionnaires of European Organization for Research and Treatment of Cancer Quality of Life |
| Level of alpha-fetoprotein (AFP) | Up to approximately 5 years | The percentage of participants with a decreased serum level of alpha-fetoprotein (AFP) after treatment |
| Number of participants with treatment-related adverse events | Up to approximately 5 years | Number of participants with treatment-related adverse events after drug initiation, as assessed by CTCAE v4.0 |
Countries
China
Contacts
Primary ContactTingbo Liang, MD PhD
Backup ContactLiang Wen, MD PhD
Outcome results
None listed