Study of Activated CIK Armed With Bispecific Antibody for Advanced Liver Cancer

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

This is a phase II Randomized comparison clinical trial of activated CIK armed with anti-CD3-MUC1/CEA/EpCAM/GPC3 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/CEA/EpCAM/GPC3 bispecific antibody for liver cancer.

Study Overview

• Status: Unknown
• Conditions: Advanced Liver Cancer
• Intervention / Treatment: Biological: Activated CIK; Biological: CIK

Detailed Description

Liver cancer is one of the most common malignancies in China, ranking fourth in all malignant tumors and third in mortality. Immunetherapy is considered to be one of the most promising means of human against cancer. This is a phase II clinical trial of single-center, randomized (1:1of targeted activation CIK and traditional CIK therapy )comparison clinical trial of activated CIK armed with anti-CD3-MUC1/CEA/EpCAM/GPC3 bispecific antibody for advanced liver cancer. The investigators plan to recruit for 80 cases patients with advanced liver cancer, the first 20 cases were directly received treatment of activated CIK, and the cases after the 20th were randomly assigned to two group，one of the two group will receive treatment of traditional CIK, and the other receive activated CIK. The result of this study was statistic and analysed with the record of Response Evaluation Criteria In Solid Tumors(RECIST1.1) evaluation standard.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jiamin Cheng, Doctor; Phone Number: 6030 +86-10-66933129; Email: chengjiamin300@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100039
      • Recruiting
      • 302 Military Hospital of China
      • Contact: Jiamin Cheng, Doctor; Phone Number: 6030 +86-10-66933129; Email: chengjiamin300@163.com
      • Principal Investigator: Yinying Lu
      • Sub-Investigator: Zhen Zeng
      • Sub-Investigator: Xuechun Lu
      • Sub-Investigator: Jiamin Cheng
      • Sub-Investigator: Zhengcheng Li
      • Sub-Investigator: Jun Hou
      • Sub-Investigator: Ting Zhang
      • Sub-Investigator: Chunping Wang
      • Sub-Investigator: Guanghua Rong
      • Sub-Investigator: Bin Yang
      • Sub-Investigator: Yan Chen
      • Sub-Investigator: Ze Liu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18-75 years old;
2. The patient is diagnosed as advanced liver cancer,MUC1/CEA/EpCAM/GPC3 is positive;
3. 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;
4. C interval of BCLC;
5. The patient can't tolerate system(systemic chemotherapy/molecular targeted therapy) or local therapies;
6. Child-Pugh Score ≤7;
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;
8. 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;
9. The expected survival time ≥4 months；
10. The patient did not took any antitumor drugs within two weeks(any antitumor drugs, Chinese patent medicine including Delisheng injection, Kanglaite injection, Aidi injection, huaier granule and Ganfule Pian);
11. ECOG Score ≤1；
12. HBV DNA<10^4copies/ml（2000IU/ml);
13. Serum albumin≥28g/L,ALT and AST≤5.0×ULN,TBIL≤1.5×ULN, electrolyte is normal, proteinuria = 0 ~ 1 +, serum creatinine≤1.5 x ULN;
14. 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≥50×10^9/L;
15. No serious disease are conflicts with the solution(such as autoimmune disease,immunodeficiency,orgen transplantation);
16. Sign the informed consent;

Exclusion Criteria:

1. Severe cirrhosis, medium or above ascites;
2. Cancer embolus in the main portal vein and first branch, Hepatic duct and first branch, hepatic vein, inferior vena cava;;
3. Patients of T cell lymphoma、myeloma,and patients are using immunosuppressant;
4. Systemic autoimmune diseases, allergic constitution or immunocompromised patients.
5. Patients of chronic diseases need immune stimulant or hormone therapy ;
6. 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;
7. Women who is pregnant or during breast feeding or plan to pregnant in 2 years,and not willing to contraception during the test;
8. Any significant clinical and laboratory abnormalities, the researchers think that affect the safety, such as: incontrollable active infection (> NCI - CTC AE v4.0 standard level 2), uncontrolled diabetes (> level 2 of NCI - CTC AE v4.0 ), hypertension and can't be controlled by two or less hypotensor(systolic pressure < 140 mmHg, diastolic pressure < 90 mmHg), grade II or above peripheral neuropathy (NCI CTC AE v4.0), grade II or above congestive heart failure (NCI CTC AE v4.0), myocardial infarction in 6 month, thyroid dysfunction (> level 2 of NCI - CTC AE v4.0), etc;
9. Patients with brain、dura mater metastases or history of psychogeny;
10. 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;
11. Patients with severe stomach/esophageal varices and need for intervention treatment;
12. Patients with abdominal fistula, gastrointestinal perforation or abdominal abscess within 4 weeks before the first treatment;
13. Patients with glomenrular filtration rate abnormal obviously(The endogenous creatinine clearance < 60 ml/min or serum creatinine > 1.5 x ULN);
14. Positive for HIV antibody;
15. Patients who are allergic to computed tomography (CT) and magnetic resonance imaging (MRI) contrast agents at the same time, can't imaging assay;
16. Patients accepted any experimental drugs or pilot medical apparatus and instruments in the past 4 weeks of first treatment;
17. Other reasons the researchers think not suitable.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Activated CIK armed with bispecific antibody treatment group; CIK cells were activated by bispecific antibody of anti-CD3-MUC1/CEA/EpCAM/GPC3	Biological: Activated CIK; Activated CIK armed with bispecific antibody were infused for 3 days，after 2 days，bispecific antibody was infused separately for 3 days
Active Comparator: Traditional CIK treatment group; CIK cells were not activated	Biological: CIK; Traditional CIK were infused for 3 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overrall survival.The time of patient from randomization to death caused by any cause.	3 years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Benhealth Biopharmaceutical (Shenzhen) Co., Ltd.
• Collaborators: Beijing 302 Hospital
• Investigators: Study Director: Yinying Lu, Doctor, Liver Cancer Diagnosis & Treatment and Research Center of 302 Military Hospital of China

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2017
• Primary Completion (Anticipated): January 27, 2021
• Study Completion (Anticipated): January 28, 2021

Study Registration Dates

• First Submitted: May 2, 2017
• First Submitted That Met QC Criteria: May 9, 2017
• First Posted (Actual): May 10, 2017

Study Record Updates

• Last Update Posted (Actual): February 1, 2021
• Last Update Submitted That Met QC Criteria: January 27, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: liver cancer; Activated CIK; MUC1/CEA/EpCAM/GPC3; Bispecfic antibody
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms
• Other Study ID Numbers: BK2016.01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Time Frame: When the study is finished
• IPD Sharing Supporting Information Type: Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No