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

April 22, 2017 updated by: Shanghai GeneChem Co., Ltd.

An Open-label, Uncontrolled, Single-arm Pilot Study to Evaluate Intratumor Injection Mediated GPC3-targeted Chimeric Antigen Receptor T Cells in Advanced Hepatocellular Carcinoma

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

10

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
      • Beijing, China
        • Recruiting
        • 302 Military Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 67 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: GPC3-CART cells
Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety of CAR-T cell infusion mediated by intratumoral injection as measured by number of participants with adverse Events
Time Frame: 6 weeks
To determine the safety and regimen limiting toxicity (RLT) of anti-GPC3 CAR-T intratumoral injection for GPC3-expressing HCC.
6 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with tumor response as measured by RECIST
Time Frame: 8 weeks]
8 weeks]
Serum cytokine levels
Time Frame: 8 weeks
Measurement of cytokines as indicators of immune response, including IL-2/IL-6/IL-10/TNF/IL-2R
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai GeneChem Co., Ltd.

Collaborators

Beijing 302 Hospital

Investigators

  • Principal Investigator: Lu Yinying, Doctor, Beijing 302 Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2017

Primary Completion (Anticipated)

March 31, 2018

Study Completion (Anticipated)

March 31, 2018

Study Registration Dates

First Submitted

April 22, 2017

First Submitted That Met QC Criteria

April 22, 2017

First Posted (Actual)

April 26, 2017

Study Record Updates

Last Update Posted (Actual)

April 26, 2017

Last Update Submitted That Met QC Criteria

April 22, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 302 GPC3-CART

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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