A Study of GPC3 Redirected Autologous T Cells for Advanced HCC
GPC3-CART
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
1 other identifier
interventional
30
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Mar 2016
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2016
CompletedFirst Submitted
Initial submission to the registry
March 11, 2016
CompletedFirst Posted
Study publicly available on registry
March 22, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2019
CompletedMarch 22, 2016
March 1, 2016
2.3 years
March 11, 2016
March 16, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
6 weeks
Secondary Outcomes (3)
Number of participants with tumor response as measured by RECIST
8 weeks
Detection of CART cells in the circulation using quantitative -PCR
8 weeks
Serum cytokine levels
8 weeks
Study Arms (1)
TAI-GPC3-CART cells
EXPERIMENTALA 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.
Interventions
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
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- Pregnant or lactating women;
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Renji Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, China
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Xu Aimin, Doctor
RenJi Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 11, 2016
First Posted
March 22, 2016
Study Start
March 1, 2016
Primary Completion
July 1, 2018
Study Completion
March 1, 2019
Last Updated
March 22, 2016
Record last verified: 2016-03