Phase IB/II Study of NRT Combined With Radiotherapy for Advanced HCC

Study Overview
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Brief Summary
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The study herein successfully developed a new immunotherapeutic approach combined with radiotherapy, and tried to proved it to be more effective and safe.

Detailed Description
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Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer-related death worldwide. The resection rate for HCC is approximately 10%-30% and the overall prognosis is very poor with a 5-year survival rate of 5%-6%. The recurrence rate is high after radical resection. In addition to surgery, radiofrequency ablation, transcatheter arterial chemoembolization (TACE), microwave ablation, cryoablation, radioactive seeds implantation, high-intensity-focused ultrasound, radiation therapy, chemotherapy and targeted drugs are available for patients with unresectable tumors; however, the efficacy of these treatments are limited and long-term prognosis in the patients is still poor. Moreover, due to serious side effects induced by treatments such as TACE, chemotherapy and targeted drugs, it may not be possible for patients to continue receiving these therapies. The study herein successfully developed a new immunotherapeutic approach combined with radiotherapy, and tried to proved it to be more effective and safe.

Official Title
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Phase IB/II Study of Personalized New Antigen Reactive Immune Cells (NRT) Combined With Radiotherapy for Advanced Hepatocellular Carcinoma Patients

Conditions
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HCC

Intervention / Treatment
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* Biological: NRT
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female or male aged 18 years and over, but no more than 75 years; Histologic or cytologic confirmation of advanced hepatocellular carcinoma; Patients with measurable lesions but can not be treated with surgery; Patients with two or over measurable lesions; ECOG≤0-2, Child-pugh A-B; Patients had not received systemic venous chemotherapy ever before; Hematology Index; Neutrophile granulocyte greater than 1.5×10^9/L; Hemoglobin greater than 10g/dL; Platelet greater than 90×10^9/L; Biochemical index Serum bilirubin not greater than 1.5x upper limit of reference range （ULN） ALT or AST not greater than 1.5x ULN Creatinine clearance no less than 60ml/min; Negative pregnancy test for women of childbearing potential; Provision of informed consent; Be able to follow the research program and follow up process; Expected survival time 3 months or more. Exclusion Criteria: Chemotherapy with experimental drug within 3 months before the start of study therapy; Have at least another primary malignant tumor; Active infection with bacterial or fungal infection; Patients with HIV infection, HCV infection, serious coronary artery disease or asthma, serious cerebrovascular disease or other diseases that the researchers think can not be entered into the group; Women who are pregnant or breast feeding; Drug abuse, clinical or psychological or social factors which will influence the informed. consent or the study implementation; May be allergic to immunotherapy; Radiotherapy and immunotherapy may not be implemented due to social or geographical factors; Weight loss greater 10% within 6 weeks before the start of study therapy; influence the safety or compliance of the patients.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Interventional Model Description: NRT+radiotherapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NRT + radiotherapy<br>HCC received NRT and radiotherapy | Biological: NRT<br>* Peripheral blood lymphocytes will be collected and neoantigen reactive T cells(NRTs) will be generated in the laboratory. NRTs 0.5 1 x 10^10, will be i.v.Q3 weeks for total 4-6 doses.<br>Radiation: Radiotherapy<br>* Radiotherapy of the major mass by dose of 5Gy/F * 10F<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Adverse Events | using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | Response Rate（RR） will be evaluated according Response Evaluation Criteria | 3, 6 and 12 months | 
| Progression free survival (PFS) | the duration of progression free survival is measured from the time of treatment to the first date that recurrent or progressive disease or for any reason of death is objectively documented | 3, 6, 9 and 12 months | 
| Overall Survival (OS) | the duration is measured from the time of treatment to the time of death | At 6, 12 and 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCC, NRT, TOMO radiotherapy