Intra-arterial (IA) therapy is generally used to treat HCC tumors that are too extensive to excise or treat with potentially curative local therapy. IA therapy takes advantage of the fact that the blood supply of HCC comes predominantly from the hepatic artery compared with the surrounding normal liver which is predominantly supplied by portal venous blood. The intent is to deprive the HCC of its blood supply, leading to the death of the tumor. Traditionally, various methods have been used to block the HCC blood supply, but improvements are needed. This study will investigate a new agent designed in the laboratory to block only tumor blood vessels, not blood vessels in the normal liver.
Genetic testing was done to identify differences between HCC tumors and normal liver, and a protein, PLVAP, was shown to be present on the blood vessels of HCC but not on the blood vessels of normal liver. An antibody, CSR02, was made that recognizes PLVAP and then the Fab portion of that antibody was combined with tissue factor, a normal human protein that initiates the clotting cascade. The result is a manufactured (recombinant) protein called CSR02-Fab-TF. Preclinical studies in a mouse model showed that infusion of an equivalent mouse protein resulted in the necrosis (death) of a transplanted human HCC. The current study is designed first, to identify a safe and optimal dose of CSR02-Fab-TF in patients , and then second, to determine the response rate of HCC tumors to the IA administration of CSR02-Fab-TF.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
43
Intra-Arterial Infusion of CSR02-Fab-TF
National Cheng Kung University Hospital (NCKUH)
Tainan, North Dist., Taiwan
RECRUITINGKoo Foundation Sun Yat-Sen Cancer Center (KFSYSCC)
Taipei, Pei-Tou Dist., Taiwan
RECRUITINGNational Taiwan University Hospital (NTUH)
Taipei, Zhongzheng Dist., Taiwan
RECRUITINGKFSYSCC
Taipei, Taiwan
RECRUITINGIncidence and severity of adverse events from intra-arterial infusion of CSR02-Fab-TF in patients with hepatoma only or largely confined to the liver, and resistant/recurrent after prior therapy
Measured by the number of treatment-emergent adverse events and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Time frame: Infusion to Day 50
HCC blood flow
HCC blood flow will be assessed by magnetic resonance imaging (MRI) on day 4 after infusion of CSR02-FabTF.
Time frame: MRI on Day 4
Determine tumor response to intra-arterial infusion of CSR02-Fab-TF
Measured by radiographic response using acceptable imaging modalities used for assessment of tumor vasculature and blood flow (MRI or CT) based on mRECIST.
Time frame: by MRI on Day 50 and then every 3 months for an average of one year.
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