A Study of GPC3-targeted T Cells by Intratumor Injection for Advanced HCC (GPC3-CART)

NCT ID: NCT03130712

Last Updated: 2017-04-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-01
• Study Completion Date: 2018-03-31

Brief Summary

In this study, CART cells are targeted to GPC3 by intratumor injected that we hope by this means could improve the local CAR-T cell numbers, meanwhile reduce the potential side effects.

Detailed Description

Patients treated with leukapheresis to obtain peripheral blood mononuclear cells, and then PBMC are purified. T cells are activated and then re-engineered to express chimeric antigen receptors (CARs) specific for GPC3. Cells are expanded in culture and returned to the participant by intratumor injection at the dose of(1-10)×106 CAR positive T cells. The cells perfusion process would only last for (1-2) min. GPC-CART cells are injected into each tumor focus only once.

Conditions

Carcinoma, Hepatocellular

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GPC3-CART cells

Group Type: EXPERIMENTAL

GPC3-CART cells

Intervention Type: DRUG

Intratumol injection as a local drug delivery pathway, so that more T cells gathered at the tumor site, less T cells to migrated to the normal tissue, thereby enhancing the efficacy of anti-tumor, reducing the potential of side effects. And GPC3-CART is a 2nd CAR, with GPC3 as the target protein, 4-1BB as a co- stimulator

Interventions

GPC3-CART cells

Intratumol injection as a local drug delivery pathway, so that more T cells gathered at the tumor site, less T cells to migrated to the normal tissue, thereby enhancing the efficacy of anti-tumor, reducing the potential of side effects. And GPC3-CART is a 2nd CAR, with GPC3 as the target protein, 4-1BB as a co- stimulator

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Advanced HCC patients with age between 18 and 69 years old;
• Persistent cancer after at least one prior standard of chemotherapy or surgery, and without high level evidence of second-line treatment;
• The intended intratumoral injection sites of tumor can be showed clear by CT or ultrasound scan, and safe access to without important neuromuscular pass;
• The ECOG score less than 1 points, and the expected survival more than 4 months;
• Recovery from previous treatment: all side effects (except hair loss) were reduced to level 1 or below, according to NCI-CTC AE version 4;
• Pregnancy test (urine beta -HCG) negative (for women of childbearing age);
• Meet one of the following conditions:

1. GPC3 was expressed in more than 15% of tumor cells (immunohistochemical method)

2. GPC3 expression in more than 30% of tumor cells (flow cytometry);

• Satisfactory organ and bone marrow function as defined by the following: (1) creatinine <1.5mg/dl; (2) albumin >2; (3) cardiac ejection fraction of >55%; (4) hemoglobin>9g/dl, bilirubin 2.0×the institution normal upper limit;
• Adequate venous access for apheresis;
• Voluntary informed consent.

Exclusion Criteria

• Pregnant or lactating women, urine pregnancy test was positive before transplantation of CAR-T cells 48 hours;
• Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary;
• Patients in the situation of: (1) 30 days before apheresis is still in the period of other antitumor drug observation; (2) patient dont recuperate from earlier acute adverse influence brought by any treatments accepted before;
• Four weeks before recruit accepted radiation therapy; Previously treatment with any gene therapy products;
• Feasibility assessment during screening demonstrates<30% transduction of target lymphocytes, or insufficient expansion (<5-fold) in response to CD3/CD28 costimulation;
• Any serious, uncontrolled diseases (including, but not limit to, unstable angina pectoris, congestive heart failure, grade III or IV cardiac disease, serious arrhythmia, liver and kidney disorders or metabolic diseases, CNS diseases);
• Patient with severe acute hypersensitive reaction;
• Forced position, can not be adjusted according to requirements;
• Severe heart, lung, liver, kidney function, blood coagulation dysfunction;
• Taking part in other clinical trials;
• Study leader considers not suitable for this tiral.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing 302 Hospital

OTHER

Sponsor Role: collaborator

Shanghai GeneChem Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lu Yinying, Doctor

Role: PRINCIPAL_INVESTIGATOR

Beijing 302 Hospital

Locations

302 Military Hospital

Beijing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Lu Yinying, Doctor

Role: CONTACT

luyinying1973@163.com

13301256799

Yu Xuejun, Master

Role: CONTACT

yuxuejun@genechem.com.cn

18616108610

Facility Contacts

Lu Yinying, Doctor

Role: primary

luyinying1973@163.com

13301256799

Other Identifiers

302 GPC3-CART

Identifier Type: -

Identifier Source: org_study_id