Study of Activated Cytokine-induced Killer Armed With Bispecific Antibody for Advanced Liver Cancer

Study Overview
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Brief Summary
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This is a phase II Randomized comparison clinical trial of activated CIK armed with anti-CD3-MUC1 bispecific antibody for advanced liver cancer. And the aim of this research is to study the clinical efficacy and safety of activated CIK armed with anti-CD3-MUC1 bispecific antibody for liver cancer.

Detailed Description
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Primary hepatocellular carcinoma is one of the most common malignancies in China, ranking fourth in all malignant tumors and third in mortality.immunotherapy is considered to be one of the most promising means of human against cancer. This is a phase II clinical trial of single- center, The investigators plan to recruit for 90 patients with advanced liver cancer,and all patients are divided into three groups.one group will receive cryotherapy, one group will receive Non-intervention therapy，and the rest one will receive mixed liquor of activated CIK and anti-CD3-MUC1 bispecific antibody together with cryotherapy. The result of this study was statistic and analysed with the record of Response Evaluation Criteria In Solid Tumors(RECIST1.1) evaluation standard.

Official Title
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Phase II Randomized Comparison Clinical Trial of Target Activated CIK for Advanced Liver Cancer

Conditions
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Advanced Liver Cancer

Intervention / Treatment
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* Biological: Activated CIK and CD3-MUC1 Bispecific Antibody in Treating Liver Cancer
* Procedure: cryotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-75 years old The patient is diagnosed as advanced liver cancer,MUC1 is positive There is at least one tumor should be measured,and length≥10mm of focus not at lymph node or length≥10mm of focus at lymph node C interval of BCLC The patient can't tolerate system(systemic chemotherapy/molecular targeted therapy) or local therapies Child-Pugh Score ≤7 If the patient received adjuvant chemotherapy after local treatment,the time should be more than 4 weeks after the end of chemotherapy, and disease progression or metastasis patients can also assigned into the group The time of surgical treatment≥ 3 months ;At the end of the intervention,radiotherapy and the end of the ablation time is more than 4 weeks The expected survival time ≥12 weeks The patient did not took any antitumor drugs within 4 weeks(any antitumor drugs, Chinese patent medicine including Delisheng injection,Kanglaite injection, Aidi injection Hepatitis B virus(HBV) DNA<10^4copies/ml（2000IU/ml) Serum albumin≥28g/L,TBIL≤1.5×ULN,electrolyte is normal, proteinuria = 0   1 +, serum creatinine≤1.5 x ULN Tests of blood,liver and kidney should meet the following criteria:WBC≥3×10^9/L,NEUT≥1×10^9/L,Hemoglobin ≥90 g/L,ANC≥1.5×109/L,PLT≥75×10^9/L No serious disease are conflicts with the solution(such as autoimmune disease,immunodeficiency,organ transplantation) Sign the informed consent Exclusion Criteria: Severe cirrhosis, medium or above ascites Cancer embolus in the main portal vein and first branch, Hepatic duct and first branch, hepatic vein, inferior vena cava Patient of second primary tumor or multiple primary cancer Patients of T cell lymphoma、myeloma,and patients are using immunosuppressant Systemic autoimmune diseases, allergic constitution or immunocompromised patients Patients of chronic diseases need immune stimulant or hormone therapy Patients of active bleeding or coagulant function abnormality（PT>16s、APTT>43s、TT>21s、INR≥2）,and patients of bleeding tendency or are receiving thrombolysis and anticoagulation and antiplatelet therapy Women who is pregnant or during breast feeding or plan to pregnant in 2 years,and not willing to contraception during the test Patients with brain、dura mater metastases or history of psychogenic Gastrointestinal bleeding in the past six months or have clear gastrointestinal bleeding tendency,such as: patients of local active ulcerative lesions, defecate occult blood + + above shall not enter into group; defecate occult blood + depend on gastroscopy Patients with severe stomach/esophageal varices and need for intervention treatment Patients with abdominal fistula, gastrointestinal perforation or abdominal abscess within 4 weeks before the first treatment Patients with glomerular filtration rate abnormal obviously(The endogenous creatinine clearance < 60 ml/min or serum creatinine > 1.5 x ULN) Positive for HIV antibody Patients who are allergic to computed tomography (CT) and magnetic resonance imaging (MRI) contrast agents at the same time, can't imaging assay Patients accepted any experimental drugs or pilot medical apparatus and instruments in the past 4 weeks of first treatment Other reasons the researchers think not suitable

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a phase II clinical trial of single-center, and it will divide into three groups.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cryotherapy<br>the maximum tumor length≥2 cm，cool down the lesion,result in degeneration, necrosis or loss of the lesion. | Procedure: cryotherapy<br>* the maximum tumor length≥2 cm，cool down the lesion,result in degeneration, necrosis or loss of the lesion.<br>|
| Active Comparator: Cryotherapy & Activated CIK and bispecific antibody<br>the maximum tumor length≥2cm, use cryotherapy. the maximum tumor length<2 cm,Biological/Vaccine:Activated CIK and bispecific antibody CIK cells was activated by PD-1 inhibitor and bispecific antibody of anti-CD3/MUC1 | Biological: Activated CIK and CD3-MUC1 Bispecific Antibody in Treating Liver Cancer<br>* CIK cells was activated by PD-1 inhibitor and bispecific antibody of anti-CD3/MUC1<br>Procedure: cryotherapy<br>* the maximum tumor length≥2 cm，cool down the lesion,result in degeneration, necrosis or loss of the lesion.<br>|
| No Intervention: No intervention<br>In this group, the patients will receive no special treatment and as a control group. The check indexes are CT scan and blood tests (including tumor markers, lymphocyte subsets and circulating tumor cell). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | ORR.The proportion of patients who had a best response rating of complete response and partial response. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | PFS.The time of patients from randomization to death caused by the progression of the tumor or any cause. | 3 years | 
| Time tumor progression | TTP.The time of patient from randomization to objective progress of the tumor. | 1 year | 
| Disease control rate | DCR.The proportion of patients who had a best response rating of complete response, partial response,or stable disease. | 1 year | 
| Overall survival | OS.The time of patient from randomization to death caused by any cause | 3 years | 
| Symptom remission rate | SRR. The proportion of symptoms are alleviated in all evaluative cases. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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activated CIK, MUC1, bispecific antibody, liver cancer