Efficacy and Safety of Immuncell-LC Group and Non-treatment Group in Hepatocelluar Carcinoma Patients

Study Overview
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Brief Summary
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To prove that the efficacy and safety of 'Green Cross CELL* Immuncell-LC group' is superior to 'non-treatment group(Control group)' in patient undergone curative resection(PEIT, RFA or operation) for hepatocellular carcinoma in Korea

Detailed Description
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Multicenter, randomized, open-labeled phase 3 clinical trial.

Official Title
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Randomized, Open-label, Multi-center and Phase 3 Clinical Trial to Compare the Efficacy and Safety of 'Green Cross CELL Immuncell-LC Group' and 'Non-treatment Group' in Patient Undergone Curative Resection(PEIT, RFA or Operation) for Hepatocellular Carcinoma in Korea

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Biological: Immuncell-LC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prior to the test, patient is fully explained about the purpose/ contents and characteristics of the testing medication, and the patient him(her)self, the guardian or the legal representative signed on written consent. The patient is more than 20 and less than 80 years old The patient is diagnosed as hepatocellular carcinoma by pathological/ radiological test and he (she) is in the stage of I or II. (refer to the attached file 10). Hepatocellular carcinoma should be shown by radiological test; on dynamic CT, dynamic MRI or on angiography. Child-Pugh Score should be less than 6 (refer to the attached file 7) No matter how the patient has been treated before, his (her) tumor should be totally removed by curative resection (PEIT, RFA or operation) in 12 weeks. (based on the agreement date for written consent) The tumor's removal should be perfectly confirmed by pathological or radiological test with the mentioned method in 3) at least 4 weeks later. ECOG Performance status (ECOG-PS) is less than 1 or equal to (refer to the exhibit 8) Patient's remaining life-time should be expected at least more than 3 months. Patient should meet below conditions by blood test, kidney and liver function test : Re-evaluation is possible during screening Leukocyte count is bigger than (3 multiply 109/L) Absolute Neutrophil Count (ANC) is bigger than or equal to 1,000/µL Hemoglobin is bigger than or equal to 8.5 g/dL Thrombocyte count is bigger than (5 multiply 1010/L) BUN and serum Creatinine is less than or equal to 1.5 multiply normal upper-limit No more disease abdominal extrahepatic transfer is confirmed by abdominal CT/ MRI Exclusion Criteria: Hepatocellular carcinoma has been transferred by pathological/ radiological test (Stage III or Stage IV, refer to the exhibit 10) The carcinoma has been invaded to main portal vein or major branch hepatic vein Child-Pugh score is over 6 Patient has serious problem with pulmonary function by sub- investigator's opinion Patient who has disease history of immune deficiency (which can be worse by immunotherapy) or auto-immune disease (ex. arthritis rheumatism, Burger's disease, multiple sclerosis and adolescent-occurred insulin dependent diabetes) Diagnosed as an immune deficiency patient Patient who has disease history of malignant tumor within 5 years before this clinical trial. (except for skin cancer, local prostate cancer or carcinoma in situ of the uterine cervix Patient who had anti-cancer medication before the clinical trial Patient who has serious disease in other organs after tumor resection. Patient has serious allergic-history by sub- investigator's opinion Patient has serious mental disease by sub- investigator's opinion Pregnant women, nursing mother or having intention of being pregnant during the clinical test Patient who participated in other clinical trial within 4 weeks before this clinical trial Patient who is incongruent to this clinical trial by sub- investigator's opinion.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immunotherapy Group<br>Adjuvant adoptive immune therapy using a CIK cell agent(Immuncell-LC) 16 times(4 treatments at a frequency of once per week, followed by 4 treatments every 2 weeks, then 4 treatments every 4 weeks, and finally 4 treatments every 8 weeks. | Biological: Immuncell-LC<br>* Activated T lymphocyte<br>|
| No Intervention: Control Group<br>Patients who had undergone curative treatment(surgical resection, radiofrequency ablation[RFA], or percutaneous ethanol injection[PEI]) for HCC of pretreatment clinical stage I or II according to the American Joint Committee on Cancer staging system(6th edition) based on radiologic imaging studies were eligible for this study with no adjuvant treatment | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence Free Survival(RFS) | RFS was measured from the date of randomization to the first recurrence or to death from any cause. | Every 3months from the baseline for 24 months and then every 3-6 months until the data cut-off date, up to LSLV(Last Subject Last Visit) | 
| Recurrence Free Survival(RFS) Rate | RFS rate was measured from the date of randomization to the first recurrence or to death from any cause. | Every 3months from the baseline for 24 months, and then every 3-6 months until the data cut-off date, up to LSLV(Last Subject Last Visit) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival(OS) | Overall survival was measured from the date of randomization until death from any cause. | Every 3months from the baseline for 24 months, and then every 3-6 months until the data cut-off date, up to LSLV(Last Subject Last Visit) | 
| Cancer-specific Survivals | Cancer-specific survival was measured from the date of randomization until death resulting from HCC. | Every 3 months from baseline for 24 months, and then every 3-6 months until the data cut-off date, up to LSLV(Last Subject Last Visit) | 
| Overall Survival(OS) Rate | Overall survival rate was measured from the date of randomization until death from any cause. | Every 3months from the baseline for 24 months, and then every 3-6 months until the data cut-off date, up to LSLV(Last Subject Last Visit) | 
| Cancer-specific Survival Rate | Cancer-specific survival rate was measured from the date of randomization until death resulting from HCC. | Every 3 months from baseline for 24 months, and then every 3-6 months until the data cut-off date, up to LSLV(Last Subject Last Visit) |