A Study of GPC3 Redirected Autologous T Cells for Advanced HCC

NCT ID: NCT02715362

Last Updated: 2016-03-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2019-03-31

Brief Summary

Intravenous infusion of CART cells in the treatment of solid tumors may be not a suitable choice. Because by intravenous infusion, T cells first entered into the blood circulation, but the number of T cells accumulated at the tumor site is limited, while the probability is high that CART cells contact with normal tissue where target protein is expressed, leading to a more potential off-target side effect. In this study, CART cells infused to the body is mediated by the method of transcatheter arterial infusion(TAI), which is one kind of tumor intervention therapy pathway. 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 from which peripheral blood mononuclear cells 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 transcatheter arterial infusion at the dose of .(1-10)×106 CAR positive T cells/kg. The cells perfusion process would last for 15min to 2 h via an ambulatory infusion pump. A single dose of 1.5 grams/m2 of cyclophosphamide will be given two days before CART cell infusion.

Conditions

Carcinoma, Hepatocellular

Study Design

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

Study Groups

TAI-GPC3-CART cells

A single dose of GPC3-CART cells will be administered by transcatheter arterial infusion(TAI) mediated as one dose infusion. The dose is 1-10x106/kg GPC3-CAR positive T cells. The infusion will be scheduled to occur 2 days after a single dose of 1.5 grams/m2 of cyclophosphamide. Patients will undergo cannula--DSA radiography--CAR-T cells perfused into hepatic artery. The cells perfusion process would last 15min to 2 h, and the specific time depends on patent's tumor-burdened state.

Group Type: EXPERIMENTAL

TAI-GPC3-CART cells

Intervention Type: DRUG

TAI 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

TAI-GPC3-CART cells

TAI 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

Other Intervention Names

Gene modified patient T cells

Eligibility Criteria

Inclusion Criteria

• GPC3 expression positive and histologically confirmed as hepatocellular carcinoma;
• Aged between 18 and 69;
• Persistent cancer after at least one prior standard of care chemotherapy, has no willing for surgery or cannot be suitable for surgery patients;
• Life expectancy greater than 6 months;
• 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;
• Without bleeding disorder or coagulation disorders;
• Dont allergy to Radiocontrast agent;
• Birth control;
• Adequate venous access for apheresis, and no other contraindications for leukapheresis;
• Voluntary informed consent is given.

Exclusion Criteria

• Pregnant or lactating women;
• 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;
• 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

Shanghai GeneChem Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xu Aimin, Doctor

Role: PRINCIPAL_INVESTIGATOR

RenJi Hospital

Locations

Renji Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xu Aimin, Doctor

Role: CONTACT

xuarmy@163.com

+86 13918183196

Yu Xuejun, Doctor

Role: CONTACT

yuxuejun@genechem.com.cn

+86 021-51320189

Facility Contacts

Xu Aimin, Doctor

Role: primary

xuarmy@163.com

86-13918183196

Yu Xuejun, Master

Role: backup

yuxuejun@genechem.com.cn

86-18616108610

Other Identifiers

GeneChem GPC3-CART

Identifier Type: -

Identifier Source: org_study_id