Study of PolyIC and PD-1 mAb in Subjects With Unresectable Hepatocellular Carcinoma

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase II Study on the Safety and Therapeutic Effect of Combination of PolyIC and PD-1 mAb in Subjects With Unresectable Hepatocellular Carcinoma

Conditions
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Carcinoma, Hepatocellular

Intervention / Treatment
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* Drug: PD-1 mAb
* Drug: PolyIC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hepatocellular carcinoma with imaging diagnosis, in barcelona stage C, or stage B but resistant/recurrent to prior local treatment (e.g., TACE). Eastern cooperative oncology group physical fitness score: 0-2. Predicted survival time≥3 months. Liver function of Child-Pugh A-B, no hepatic encephalopathy or physical examined ascites. 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 Patients will be informed consent, and understand and are willing to cooperate with the trial and sign related documents. Exclusion Criteria: 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. Received the treatment of polyIC or immune checkpoint inhibitors (e.g., PD-1/PD-L1 mAb or CTLA-4 mAb) in last 2 years. 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. Received any corticosterone or immunosuppressive drug in last 2 weeks. Toxicity induced by previous anti-tumor therapies has not returned to the status of baseline or stability. HIV positive (including previous anti-retroviral therapy), active HCV infection or active syphilis. Any severe liver disease (e.g., severe liver cirrhosis, severe liver adenoma) Any active or recurrent autoimmune disease. Any interstitial pneumonia, non-infectious pneumonia, or uncontrolled systemic disease (e.g., uncontrolled hypertension or diabetes). Severe cardiovascular risk factors. Has a history of allogeneic stem cell transplantation or organ transplantation. Imaging confirmed brain or meninges metastases. Has the plan of pregnancy, or lactation. Any kind of psychiatric disease or laboratory test abnormality that may result in the subject's failure to fully comply with the laboratory protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 'PolyIC plus PD-1 mAb' and 'PD-1 mAb'<br>'PolyIC plus PD-1 mAb' group: PolyIC, 2mg, i.m., every other day, for three weeks. PD-1 mAb, 200mg, i.v., every three weeks. 'PD-1 mAb' group: PD-1 mAb, 200mg, i.v., every three weeks. | Drug: PD-1 mAb<br>* Intravenous infusion of PD-1 mAb, 200mg, once a time, every three weeks.<br>* Other names: Programmed cell death-1 monoclonal antibody;Drug: PolyIC<br>* Intramuscular injection of polyIC, 2mg, every other day, for three weeks.<br>* Other names: Polyinosinic-polycytidylic acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Percentage of patients whose cancer shrinks or disappears after treatment | Up to approximately 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate (DCR) | Percentage of patients whose cancer doesn't progress after treatment | Up to approximately 5 years | 
| Progression free survival (PFS) | The percentage of people does not get worse for a period of time after diagnosis | Up to approximately 5 years | 
| Overall survival (OS) | The percentage of people still alive for a given period of time after diagnosis | Up to approximately 5 years | 
| Number of participants with treatment-related adverse events | Number of participants with treatment-related adverse events after drug initiation, as assessed by CTCAE v4.0 | Up to approximately 5 years | 
| Percentage of participants with a better life quality | 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 | Up to approximately 5 years | 
| Level of alpha-fetoprotein (AFP) | The percentage of participants with a decreased serum level of alpha-fetoprotein (AFP) after treatment | Up to approximately 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular carcinoma, Polyinosinic-polycytidylic acid, PD-1 mAb