- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02715362
A Study of GPC3 Redirected Autologous T Cells for Advanced HCC (GPC3-CART)
March 16, 2016 updated by: Shanghai GeneChem Co., Ltd.
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
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.
Study Overview
Status
Unknown
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Anticipated)
30
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
- Name: Xu Aimin, Doctor
- Phone Number: +86 13918183196
- Email: xuarmy@163.com
Study Contact Backup
- Name: Yu Xuejun, Doctor
- Phone Number: +86 021-51320189
- Email: yuxuejun@genechem.com.cn
Study Locations
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Shanghai
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Shanghai, Shanghai, China
- Recruiting
- Renji Hospital, Shanghai Jiao Tong University School of Medicine
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Contact:
- Yu Xuejun, Master
- Phone Number: 86-18616108610
- Email: yuxuejun@genechem.com.cn
-
Contact:
- Xu Aimin, Doctor
- Phone Number: 86-13918183196
- Email: xuarmy@163.com
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Principal Investigator:
- Xu Aimin, Doctor
-
-
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
18 years to 69 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
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: 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.
|
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
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety of CAR-T cell infusion mediated by TAI 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 transcatheter arterial infusion (TAI) for GPC3-expressing HCC.
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6 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Number of participants with tumor response as measured by RECIST
Time Frame: 8 weeks
|
8 weeks
|
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Detection of CART cells in the circulation using quantitative -PCR
Time Frame: 8 weeks
|
8 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Xu Aimin, Doctor, Renji 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
March 1, 2016
Primary Completion (Anticipated)
July 1, 2018
Study Completion (Anticipated)
March 1, 2019
Study Registration Dates
First Submitted
March 11, 2016
First Submitted That Met QC Criteria
March 16, 2016
First Posted (Estimate)
March 22, 2016
Study Record Updates
Last Update Posted (Estimate)
March 22, 2016
Last Update Submitted That Met QC Criteria
March 16, 2016
Last Verified
March 1, 2016
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- GeneChem GPC3-CART
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
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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