Clinical trial NCT02715362: A Study of GPC3 Redirected Autologous T Cells for Advanced HCC
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
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Carcinoma, Hepatocellular
Keywords: immunotherapy GPC3 CAR-T HCC
Lead sponsor: Shanghai GeneChem Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2016-03-22
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Safety of CAR-T cell infusion mediated by TAI as measured by number of participants with adverse Events
timeFrame: 6 weeks
Secondary outcomes:
measure: Number of participants with tumor response as measured by RECIST
timeFrame: 8 weeks
measure: Detection of CART cells in the circulation using quantitative -PCR
timeFrame: 8 weeks
measure: Serum cytokine levels
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Renji Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
affiliation: RenJi Hospital
name: Xu Aimin, Doctor
role: PRINCIPAL_INVESTIGATOR
References: