This is an open label, fixed dose, phase Ib trial of anti-CEA CAR-T cell infusions delivered via the hepatic artery or splenic vein using the Surefire Infusion System (SIS) for patients with CEA-expressing liver metastases or pancreas cancer.
Patients undergo 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 CEA. Cells are expanded in culture and returned to the patient by percutaneous hepatic artery infusion at specific cell doses. Prior to the first dose, each patient will undergo diagnostic angiography to verify suitable arterial anatomy. Three anti-CEA CAR-T doses per patient are planned at 1-week intervals. Low dose interleukin-2 will be given via an ambulatory infusion pump for 4 weeks. Normal liver and tumor biopsies will be obtained at the time of the initial diagnostic angiogram and during the final session following the 3rd CAR-T infusion. Patients with CEA+ liver metastases who exhibit in-liver control following CAR-T therapy who also have CEA+ primary pancreatic tumors may be eligible to receive direct intrapancreatic CAR-T retrograde venous infusions. A maximum of 2 infusions will be delivered. No additional IL-2 will be given and there will be no additional biopsies.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
5
Gene modified patient T cells
University of Colorado Hospital
Aurora, Colorado, United States
Roger Williams Medical Center
Providence, Rhode Island, United States
Safety of CAR-T cell hepatic artery infusions delivered using the Surefire Infusion System (SIS) as Measured by Number of Participants with Adverse Events
To determine the safety and regimen limiting toxicity (RLT) of anti-CEA CAR-T hepatic artery infusions (HAI) via the Surefire Infusion System (SIS) for CEA-expressing liver metastases
Time frame: 10 weeks
Radiographic treatment response by MRI
Changes in tumor size
Time frame: 10 weeks
Radiographic treatment response by PET
Changes in tumor metabolic activity
Time frame: 10 weeks
CAR-T detection in liver tumors
Quantification of CAR-T cells in liver tumor core biopsies
Time frame: 10 weeks
CAR-T detection in normal liver tissue
Quantification of CAR-T cells in normal liver core biopsies
Time frame: 10 weeks
CAR-T detection in extrahepatic sites
Quantification of CAR-T in blood samples
Time frame: 10 weeks
Serum Cytokine Levels
Measurement of cytokines as indicators of immune response
Time frame: 10 weeks
CEA level
Measurement of serum tumor marker (ng/ml)
Time frame: 10 weeks
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Tumor biopsy
Assessment of tumor necrosis and fibrosis
Time frame: 10 weeks
Safety of Direct Intrapancreatic CAR-T Retrograde Venous Infusions (RVI) Delivered Using the Surefire Infusion System (SIS)
RVI via the Surefire Infusion System (SIS) for CEA+ Primary Pancreatic Tumors Following In-liver Disease Control
Time frame: 10 weeks