Ignite Creation Date:
2024-05-06 @ 7:34 PM
Last Modification Date:
2024-10-26 @ 3:09 PM
Study NCT ID:
NCT06054308
Status:
WITHDRAWN
Last Update Posted:
2023-10-13
First Post:
2023-09-19
Brief Title:
Mesothelin-targeted CAR-T Cells as a Neo-adjuvant Treatment in Patients With Resectable Pancreatic Cancers a Feasibility Study
Sponsor:
Chinese University of Hong Kong
Organization:
Chinese University of Hong Kong
Study Overview
Official Title:
Mesothelin-targeted CAR-T Cells as a Neo-adjuvant Treatment in Patients With Resectable Pancreatic Cancers a Feasibility Study
Status:
WITHDRAWN
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Unable to obtain Clinical Trial Certificate due to tech Unable to obtain Clinical Trial Certificate due to technical difficulties
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CART
Brief Summary:
Pancreatic ductal adenocarcinoma PDAC is a cancer of grave prognosis with only about 10 of patients alive at 5 years after diagnosis Primary surgical resection is feasible in about 10-15 of patients with an early-stage disease Another 30-35 of patients have locally advanced disease with invasion into major vasculature but without detectable metastases Surgery offers a chance of cure The introduction of adjuvant multi-agent chemotherapy has improved prognosis after surgery
In the management of patients with PDAC the role of neoadjuvant therapy is less certain Neoadjuvant therapy for pancreatic cancer can in theory control early systemic spread and improve rate of having no macroscopic or microscopic residual tumor R0 resection In the The European Study Group for Pancreatic Cancer ESPAC-5 study neoadjuvant combination chemotherapy did not increase rate of resection who had borderline-resectable disease but appears to improve overall survival OS
Chimeric antigen receptor CAR T-cell therapy may represent a new paradigm in the treatment of pancreatic cancer Mesothelin MSLN is a 40 kDa membrane protein not expressed in normal cells but highly expressed in a variety of cancer cells such as mesothelioma lung breast ovarian gastric and pancreatic cancer MSLN is expressed about 80 of PDAC
There are several immunotherapies targeting MSLN for PDAC treatment including antibody-based drugs monoclonal antibodies antibody-drug conjugates immunotoxins vaccines and CAR-T cell therapy
The safety of CAR-T cells targeting MSLN in the treatment of cancers has also been verified in several clinical trials on lung cancers NCT01583686 NCT02414269 NCT01355965 Professor Li Pengs group at the Chinese Academy of Science designed third generation CAR-T cells targeting MSLN and validated their use in both human PDAC cell lines animal models and in 4 patients with advanced malignancies In a 42-year-old man with metastatic PDAC the MSLN targeted CAR-T treatment led to complete response follow several hepatic artery infusion and intravenous infusion These early cases confirmed the safety of these MSLN targeted CAR-T cells
In the current proposed feasibility study the researcher hypothesise that Endoscopic ultrasound EUS-guided injection of MSLN targeted CAR-T cells into PDAC can induce a tumor response improve rate of R0 resection and translate into better patient survival
In the management of patients with PDAC the role of neoadjuvant therapy is less certain Neoadjuvant therapy for pancreatic cancer can in theory control early systemic spread and improve rate of having no macroscopic or microscopic residual tumor R0 resection In the The European Study Group for Pancreatic Cancer ESPAC-5 study neoadjuvant combination chemotherapy did not increase rate of resection who had borderline-resectable disease but appears to improve overall survival OS
Chimeric antigen receptor CAR T-cell therapy may represent a new paradigm in the treatment of pancreatic cancer Mesothelin MSLN is a 40 kDa membrane protein not expressed in normal cells but highly expressed in a variety of cancer cells such as mesothelioma lung breast ovarian gastric and pancreatic cancer MSLN is expressed about 80 of PDAC
There are several immunotherapies targeting MSLN for PDAC treatment including antibody-based drugs monoclonal antibodies antibody-drug conjugates immunotoxins vaccines and CAR-T cell therapy
The safety of CAR-T cells targeting MSLN in the treatment of cancers has also been verified in several clinical trials on lung cancers NCT01583686 NCT02414269 NCT01355965 Professor Li Pengs group at the Chinese Academy of Science designed third generation CAR-T cells targeting MSLN and validated their use in both human PDAC cell lines animal models and in 4 patients with advanced malignancies In a 42-year-old man with metastatic PDAC the MSLN targeted CAR-T treatment led to complete response follow several hepatic artery infusion and intravenous infusion These early cases confirmed the safety of these MSLN targeted CAR-T cells
In the current proposed feasibility study the researcher hypothesise that Endoscopic ultrasound EUS-guided injection of MSLN targeted CAR-T cells into PDAC can induce a tumor response improve rate of R0 resection and translate into better patient survival
Detailed Description:
In the management of patients with PDAC the role of neoadjuvant therapy is less certain Neoadjuvant therapy for pancreatic cancer can in theory control early systemic spread and improve rate of R0 resection 2 In the ESPAC-5 study neoadjuvant combination chemotherapy did not increase rate of resection who had borderline-resectable disease but appears to improve overall survival OS 3 The Charité Onkologie CONKO-007 trial showed that the addition of radiation to chemotherapy improved R0 resection rate and complete pathological response pCR but did not impact on OS 4
Chimeric antigen receptor CAR T-cell therapy may represent a new paradigm in the treatment of pancreatic cancer Mesothelin MSLN is a 40 kDa membrane protein minimally expressed in normal cells but highly expressed in a variety of cancer cells such as mesothelioma lung breast ovarian gastric and pancreatic cancer MSLN is expressed in about 80 of PDAC
Mesothelin is the receptor of tumor antigen CA-125 also known as MUC16 Tumor expressing CA-125 can combine with mesothelin on the surface of mesothelial cells in pleural or peritoneal cavity resulting in increased cell adhesion and promoting metastatic diffusion 5 In pancreatic cancers mesothelin plays a role in tumorigenesis by increasing cell proliferation migration and S phase cell population Its limited expression in normal human tissues and high expression in many cancers make it an attractive tumor-related antigen for cancer treatment 6
There are several immunotherapies targeting MSLN for PDAC treatment including antibody-based drugs monoclonal antibodies antibody-drug conjugates immunotoxins vaccines and CART cell therapy For example the recombinant protein preparation SS1dsFvPE38 SS1P which is composed of high affinity Fv variable fragment targeting MSLN and Pseudomonas exotoxin A PE fusion has entered clinical trials as a drug 7 There is also an antibody-drug conjugate Anetumab ravtansine BAY 94-9343 which is made by conjugating human anti-MSLN antibody with maytansinol tubulin inhibitor DM4 through a connector containing disulfide bond In vivo anetumab ravtansine is specifically localized in tumors that express MSLN and inhibits the growth of pancreatic cancer ovarian cancer mesothelioma and other tumors The safety of CAR-T cells targeting MSLN in the treatment of cancers has also been verified in several clinical trials on lung cancers NCT01583686 NCT02414269 NCT01355965 Professor Li Pengs group at the Chinese Academy of Science designed third generation CAR-T cells targeting MSLN and validated their use in both human PDAC cell lines animal models and in 4 patients with advanced malignancies In a 42-year-old man with metastatic PDAC the MSLN targeted CAR-T treatment led to complete response following several hepatic artery infusion and intravenous infusion These early cases confirmed the safety of these MSLN targeted CAR-T cells
In the current proposed feasibility study the researcher hypothesize that EUS-guided injection of MSLN targeted CAR-T cells into PDAC can induce a tumor response improve rate of R0 resection and translate into better patient survival
Chimeric antigen receptor CAR T-cell therapy may represent a new paradigm in the treatment of pancreatic cancer Mesothelin MSLN is a 40 kDa membrane protein minimally expressed in normal cells but highly expressed in a variety of cancer cells such as mesothelioma lung breast ovarian gastric and pancreatic cancer MSLN is expressed in about 80 of PDAC
Mesothelin is the receptor of tumor antigen CA-125 also known as MUC16 Tumor expressing CA-125 can combine with mesothelin on the surface of mesothelial cells in pleural or peritoneal cavity resulting in increased cell adhesion and promoting metastatic diffusion 5 In pancreatic cancers mesothelin plays a role in tumorigenesis by increasing cell proliferation migration and S phase cell population Its limited expression in normal human tissues and high expression in many cancers make it an attractive tumor-related antigen for cancer treatment 6
There are several immunotherapies targeting MSLN for PDAC treatment including antibody-based drugs monoclonal antibodies antibody-drug conjugates immunotoxins vaccines and CART cell therapy For example the recombinant protein preparation SS1dsFvPE38 SS1P which is composed of high affinity Fv variable fragment targeting MSLN and Pseudomonas exotoxin A PE fusion has entered clinical trials as a drug 7 There is also an antibody-drug conjugate Anetumab ravtansine BAY 94-9343 which is made by conjugating human anti-MSLN antibody with maytansinol tubulin inhibitor DM4 through a connector containing disulfide bond In vivo anetumab ravtansine is specifically localized in tumors that express MSLN and inhibits the growth of pancreatic cancer ovarian cancer mesothelioma and other tumors The safety of CAR-T cells targeting MSLN in the treatment of cancers has also been verified in several clinical trials on lung cancers NCT01583686 NCT02414269 NCT01355965 Professor Li Pengs group at the Chinese Academy of Science designed third generation CAR-T cells targeting MSLN and validated their use in both human PDAC cell lines animal models and in 4 patients with advanced malignancies In a 42-year-old man with metastatic PDAC the MSLN targeted CAR-T treatment led to complete response following several hepatic artery infusion and intravenous infusion These early cases confirmed the safety of these MSLN targeted CAR-T cells
In the current proposed feasibility study the researcher hypothesize that EUS-guided injection of MSLN targeted CAR-T cells into PDAC can induce a tumor response improve rate of R0 resection and translate into better patient survival
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None