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

Carcinoma, Hepatocellular Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03732547
• Other study ID #: CISLD-1
• Status: Recruiting
• Phase: Phase 2
• Start date: October 22, 2018
• Est. completion date: October 22, 2023

Study information

• Verified date: October 2018
• Source: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Contact: Tingbo Liang, MD PhD
• Phone: +8615088682641
• Email: liangtingbo[@]zju.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: October 22, 2023
• Est. primary completion date: October 22, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Drug:
• PD-1 mAb
Intravenous infusion of PD-1 mAb, 200mg, once a time, every three weeks.
• PolyIC
Intramuscular injection of polyIC, 2mg, every other day, for three weeks.

Locations

Country	Name	City	State
China	The second affiliated hospital of Zhejiang University	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Second Affiliated Hospital, School of Medicine, Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR)	Percentage of patients whose cancer shrinks or disappears after treatment	Up to approximately 5 years
Secondary	Disease control rate (DCR)	Percentage of patients whose cancer doesn't progress after treatment	Up to approximately 5 years
Secondary	Progression free survival (PFS)	The percentage of people does not get worse for a period of time after diagnosis	Up to approximately 5 years
Secondary	Overall survival (OS)	The percentage of people still alive for a given period of time after diagnosis	Up to approximately 5 years
Secondary	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
Secondary	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
Secondary	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