A Study of Chimeric Antigen Receptor T Cells Combined With Interventional Therapy in Advanced Liver Malignancy

Carcinoma, Hepatocellular Clinical Trial

Official title:

A Single-arm Pilot Clinical Study of Chimeric Antigen Receptor T Cells Combined With Interventional Therapy in Advanced Liver Malignancy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02959151
• Other study ID #: CAR-T for liver cancer
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: November 6, 2016
• Last updated: November 7, 2016
• Start date: July 2016
• Est. completion date: July 2018

Study information

• Verified date: November 2016
• Source: Shanghai GeneChem Co., Ltd.
• Contact: Wentao Li, doctor
• Phone: +86 18017312650
• Email: liwentao98[@]126.com
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: July 2018
• Est. primary completion date: January 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 69 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Colorectal Cancer Metastatic
• Colorectal Neoplasms
• Neoplasms
• Pancreatic Cancer Metastatic
• Pancreatic Neoplasms

Intervention

Drug:
• CAR-T cell
CAR-T cells are generated by T cells from the patients or a suitable donor transfected by CAR-lentivirus vectors. There are three options for CAR-targets: GPC3 for hepatocellular carcinoma;mesothelin for pancreatic cancer metastatic; CEA for colorectal cancer metastatic.

Locations

Country	Name	City	State
China	Shanghai Tumor Hospital	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai GeneChem Co., Ltd.	Shanghai Cancer Hospital, China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with adverse event	adverse event is evaluated with CTCAE, version 4.0	6 weeks	Yes
Secondary	Number of patients with tumor response	summarize tumor response by overall response rates	8 weeks	No
Secondary	Detection of transferred T cells in the circulation using quantitative -PCR		8 weeks	No