Clinical trial NCT02959151: A Study of Chimeric Antigen Receptor T Cells Combined With Interventional Therapy in Advanced Liver Malignancy
Official title: A Single-arm Pilot Clinical Study of Chimeric Antigen Receptor T Cells Combined With Interventional Therapy in Advanced Liver Malignancy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Carcinoma, Hepatocellular
Pancreatic Cancer Metastatic
Colorectal Cancer Metastatic
Lead sponsor: Shanghai GeneChem Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Shanghai Cancer Hospital, China
First posted: 2016-11-08
Enrollment: 20
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: The purpose of this study is to collect the date on the safety and potential effectiveness of CART cells combined with interventional therapy in patients with advanced liver malignancy.

Detailed description: Designer T cells are prepared by PBMC which from patients or suitable donator by leukapheresis, and then activated and re-engineered to express chimeric antigen receptors (CARs). There are three options for CAR-targets: GPC3 for hepatocellular carcinoma; mesothelin for pancreatic cancer metastatic; CEA for colorectal cancer metastatic. Cells are expanded in culture and returned to the participant by vascular interventional therapy or by intra-tumor injection at the dose of （1.25\~4）×107 CAR positive T cells/cm3 tumor bulk. The volume of cell products and the time of cell perfusion process lasted would depend on the ways of cell perfused.

Eligibility criteria: Inclusion Criteria:

* tumor histological examination confirmed as GPC3/ mesothelin/CEA positive expression;
* 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) cardiac ejection fraction of \>55%; (3) hemoglobin\>9g/dl, bilirubin 2.0×the institution normal upper limit
* without bleeding disorder or coagulation disorders
* Don't 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: Number of patients with adverse event
timeFrame: 6 weeks
Secondary outcomes:
measure: Number of patients with tumor response
timeFrame: 8 weeks
measure: Detection of transferred T cells in the circulation using quantitative -PCR
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Tumor Hospital
state: Shanghai
Study officials:
affiliation: Fudan University
name: Wentao Li, doctor
role: PRINCIPAL_INVESTIGATOR
References: