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A Study of GPC3 Redirected Autologous T Cells for Advanced HCC (GPC3-CART)

Primary Purpose

Carcinoma, Hepatocellular

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
TAI-GPC3-CART cells
Sponsored by
Shanghai GeneChem Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma, Hepatocellular focused on measuring immunotherapy GPC3 CAR-T HCC

Eligibility Criteria

18 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Renji Hospital, Shanghai Jiao Tong University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TAI-GPC3-CART cells

Arm Description

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.

Outcomes

Primary Outcome Measures

Safety of CAR-T cell infusion mediated by TAI as measured by number of participants with adverse Events
To determine the safety and regimen limiting toxicity (RLT) of anti-GPC3 CAR-T transcatheter arterial infusion (TAI) for GPC3-expressing HCC.

Secondary Outcome Measures

Number of participants with tumor response as measured by RECIST
Detection of CART cells in the circulation using quantitative -PCR
Serum cytokine levels
Measurement of cytokines as indicators of immune response, including IL-2/IL-6/IL-10/TNF/IL-2R

Full Information

First Posted
March 11, 2016
Last Updated
March 16, 2016
Sponsor
Shanghai GeneChem Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT02715362
Brief Title
A Study of GPC3 Redirected Autologous T Cells for Advanced HCC
Acronym
GPC3-CART
Official Title
An Open-label, Uncontrolled, Single-arm Pilot Study to Evaluate Vascular Interventional Therapy Mediated GPC3-targeted Chimeric Antigen Receptor T Cells in Advanced Hepatocellular Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Unknown status
Study Start Date
March 2016 (undefined)
Primary Completion Date
July 2018 (Anticipated)
Study Completion Date
March 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai GeneChem Co., Ltd.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Hepatocellular
Keywords
immunotherapy GPC3 CAR-T HCC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TAI-GPC3-CART cells
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
TAI-GPC3-CART cells
Other Intervention Name(s)
Gene modified patient T cells
Intervention Description
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
Primary Outcome Measure Information:
Title
Safety of CAR-T cell infusion mediated by TAI as measured by number of participants with adverse Events
Description
To determine the safety and regimen limiting toxicity (RLT) of anti-GPC3 CAR-T transcatheter arterial infusion (TAI) for GPC3-expressing HCC.
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Number of participants with tumor response as measured by RECIST
Time Frame
8 weeks
Title
Detection of CART cells in the circulation using quantitative -PCR
Time Frame
8 weeks
Title
Serum cytokine levels
Description
Measurement of cytokines as indicators of immune response, including IL-2/IL-6/IL-10/TNF/IL-2R
Time Frame
8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xu Aimin, Doctor
Phone
+86 13918183196
Email
xuarmy@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yu Xuejun, Doctor
Phone
+86 021-51320189
Email
yuxuejun@genechem.com.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xu Aimin, Doctor
Organizational Affiliation
RenJi Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Renji Hospital, Shanghai Jiao Tong University School of Medicine
City
Shanghai
State/Province
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xu Aimin, Doctor
Phone
86-13918183196
Email
xuarmy@163.com
First Name & Middle Initial & Last Name & Degree
Yu Xuejun, Master
Phone
86-18616108610
Email
yuxuejun@genechem.com.cn
First Name & Middle Initial & Last Name & Degree
Xu Aimin, Doctor

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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A Study of GPC3 Redirected Autologous T Cells for Advanced HCC

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