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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02715362
Recruitment Status : Unknown
Verified March 2016 by Shanghai GeneChem Co., Ltd..
Recruitment status was:  Recruiting
First Posted : March 22, 2016
Last Update Posted : March 22, 2016
Sponsor:
Information provided by (Responsible Party):
Shanghai GeneChem Co., Ltd.

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.

Condition or disease Intervention/treatment Phase
Carcinoma, Hepatocellular Drug: TAI-GPC3-CART cells Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : March 2016
Estimated Primary Completion Date : July 2018
Estimated Study Completion Date : March 2019

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.
Drug: 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
Other Name: Gene modified patient T cells




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Number of participants with tumor response as measured by RECIST [ Time Frame: 8 weeks ]
  2. Detection of CART cells in the circulation using quantitative -PCR [ Time Frame: 8 weeks ]
  3. 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



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Ages Eligible for Study:   18 Years to 69 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02715362


Contacts
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Contact: Xu Aimin, Doctor +86 13918183196 xuarmy@163.com
Contact: Yu Xuejun, Doctor +86 021-51320189 yuxuejun@genechem.com.cn

Locations
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China, Shanghai
Renji Hospital, Shanghai Jiao Tong University School of Medicine Recruiting
Shanghai, Shanghai, China
Contact: Xu Aimin, Doctor    86-13918183196    xuarmy@163.com   
Contact: Yu Xuejun, Master    86-18616108610    yuxuejun@genechem.com.cn   
Principal Investigator: Xu Aimin, Doctor         
Sponsors and Collaborators
Shanghai GeneChem Co., Ltd.
Investigators
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Principal Investigator: Xu Aimin, Doctor RenJi Hospital
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Responsible Party: Shanghai GeneChem Co., Ltd.
ClinicalTrials.gov Identifier: NCT02715362    
Other Study ID Numbers: GeneChem GPC3-CART
First Posted: March 22, 2016    Key Record Dates
Last Update Posted: March 22, 2016
Last Verified: March 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Shanghai GeneChem Co., Ltd.:
immunotherapy GPC3 CAR-T HCC
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases