Anti-GPC3 CAR T for Treating Patients With Advanced HCC

• ClinicalTrials.gov Identifier: NCT02395250
• Recruitment Status: Completed
• First Posted: March 23, 2015
• Last Update Posted: August 28, 2019
• Sponsor: RenJi Hospital
• Information provided by (Responsible Party): RenJi Hospital

Study Description

Brief Summary:

The purpose of this study is to determine whether autologous T cells bearing chimeric antigen receptor that can specifically recognize glypican-3 (GPC3) is safe and effective for patients with relapsed or refractory hepatocellular carcinoma (HCC).

Condition or disease	Intervention/treatment	Phase
Hepatocellular Carcinoma	Biological: anti-GPC3 CAR T	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Autologous T Cells Redirected to GPC3 for Treating Patients With Advanced HCC
• Actual Study Start Date: March 2015
• Actual Primary Completion Date: June 2016
• Actual Study Completion Date: November 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: anti-GPC3 CAR T	Biological: anti-GPC3 CAR T; Other Name: CAR T cells redirected to Glypican-3 in cancer cells

Outcome Measures

Primary Outcome Measures :

1. Adverse events attributed to the administration of the anti-GPC3 CAR T cells [ Time Frame: 2 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria:

1. Age of 18-70 years;
2. Pathologically confirmed advanced hepatocellular carcinoma (HCC);
3. ≥1 measurable target lesion per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1);
4. Tumor tissue positive for GPC3 expression per immunohistochemical staining (IHC) assay;
5. Estimated survival > 12 weeks;
6. Child-Pugh grade A;
7. ECOG performance score of 0-1;
8. HBV-DNA < 200 IU/mL if positive for HBsAg or HBcAb. Patients positive for HBsAg shall receive anti-viral treatment per "The guideline of prevention and treatment for chronic hepatitis B: a 2015 update";
9. Have adequate venous access for apheresis or venous blood collection;
10. White blood cells ≥ 2.5 x 109/L, platelet ≥ 60×109/L, haemoglobin ≥ 9.0 g/dL, lymphocyte ≥ 0.4×109/L
11. Serum albumin ≥ 30 g/dL, serum lipase and amylase≤1.5 upper limit of normal (ULN), serum creatinine ≤ 1.5 ULN and endogenous creatinine clearance ≥ 40mL/min, ALT and AST ≤ 5 ULN, Serum total bilirubin ≤ 2.5 ULN, Prothrombin Time is less than 4s longer than normal;
12. Negative serum pregnancy test within 14 days before CAR T infusion, and with willingness to use reliable contraceptive methods to avoid pregnancy until 12 months after CAR T infusions for females of childbearing age; Having undergone sterilization procedure or with willingness to use reliable contraceptive methods to avoid pregnancy for males with female partner of childbearing age during the study;
13. Able to understand and sign the informed consent form

Exclusion criteria:

If the patient meets any of the exclusion criteria, the patient must be excluded from the study.

1. Pregnant or lactating female patients;
2. Positive serum tests for HCV, HIV, or syphilis;
3. Presence of HBV/HCV coinfection;
4. Presence of any uncontrollable active infection, such as, but not limited to, active tuberculosis
5. History of systemic administration of steroids (not including inhaled steroids), or other immunosuppressant drugs within 2 weeks before apheresis;
6. History of allergy to immunotherapy and related drugs, or β-lactam antibiotics, or history of other severe allergy;
7. History or current presence of hepatic encephalopathy;
8. Presence of ascites with clinical significance that is defined as positive focused physical examination for ascites, or ascites that requires treatment intervention (not including any ascites shown on image examinations without the need for clinical intervention);
9. ≥ 50% of normal liver occupied with HCC tumor tissue, or presence of tumor thrombus in the portal vein, or mesenteric vein, or inferior vena based on image analysis;
10. Presence of HCC metastatic lesion in the central nervous system, or presence of other diseases of central nervous system with clinical significance;
11. Presence of heart disease that requires treatment intervention, or poorly controlled hypertension (systolic pressure > 160 mmHg, or diastolic pressure > 100 mmHg);
12. Presence of active auto-immune disease that requires immunosuppressant treatment;
13. History of organ transplantation or currently on the waiting list for organ transplantation, including, but not limited to, liver transplantation;
14. Anti-HCC therapies including, but not limited to, surgical resection, interventional therapy, radiation therapy, chemotherapy, and immunotherapy, within 2 weeks before apheresis;
15. History of receiving anti-PD-1 or anti-PD-L1 monoclonal antibodies, or other immunotherapy;
16. History of other malignancies in the past 5 years, or presence of other active malignancies (not including cervical cancer in situ and basal cell carcinomas);
17. Presence of other serious diseases or conditions, including uncontrolled diabetes (HbA1c > 7% with treatment); severe cardiac dysfunction with LVEF < 45%; myocardial infarction, unstable angina, or unstable arrhythmia in the past 6 months pulmonary embolism; chronic obstructive pulmonary disease; interstitial lung disease; forced expiratory volume in 1 second (FEV1) < 60%, gastric ulcer; history of gastrointestinal bleeding, or confirmed tendency for gastrointestinal bleeding;
18. Determined by the investigator to be lack of compliance for the study.

Contacts and Locations

Locations

China, Shanghai

Shanghai Cancer Institute

Xuhui, Shanghai, China, 200032

Sponsors and Collaborators

RenJi Hospital

Investigators

• Study Director: Bo Zhai, MD; Renji

More Information

• Responsible Party: RenJi Hospital
• ClinicalTrials.gov Identifier: NCT02395250
• Other Study ID Numbers: RJ-20150313
• First Posted: March 23, 2015
• Last Update Posted: August 28, 2019
• Last Verified: November 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Carcinoma, Hepatocellular; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases