CSR02-Fab-TF as Hepatic Intra-arterial Therapy in Intermediate Stage B or Limited Advanced Stage C Hepatocellular Carcinoma (HCC): Dose-Escalation Study to Assess Safety and Tolerability
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.
• Age ≥ 18 years
• Diagnosis of HCC by at least one of the following criteria:
‣ Histological confirmation;
⁃ Magnetic resonance imaging (MRI) or computerized tomography (CT) consistent with liver cirrhosis AND at least one solid liver lesion \> 1 cm with intense contrast uptake during the arterial phase followed by contrast washout during the venous phase regardless of alpha-fetal protein (AFP) level
• Barcelona Clinic Liver Cancer (BCLC) Intermediate Stage B or limited Advanced Stage C (see Protocol Section 3.1). Patients with Stage C disease should have received or been offered and chosen not to receive systemic therapy
• Inadequate response to prior liver-directed therapy (e.g., TACE, bland embolization, Y90, ablation, radiation therapy) to the same targeted area or progressive disease after prior liver-directed therapy) or to one or more systemic therapies
• Not a candidate for curative resection, liver transplantation, or percutaneous ablation (See Protocol Appendix 3)
• Eastern Collective Oncology Group (ECOG) performance status ≤1 (See Protocol Appendix 5)
• Adequate laboratory parameters, including:
‣ Serum total bilirubin ≤ 2x ULN
⁃ Alkaline phosphatase, aspartate aminotransferase (AST) and aspartate aminotransferase (ALT) \< 5 x ULN;
⁃ Serum creatinine ≤ 1.5 mg/dL;
⁃ Prothrombin time (international normalized ratio; INR) ≤ 1.5;
⁃ Absolute neutrophil count \> 1000/μL;
⁃ Platelet count \> 75,000/μL;
⁃ Hgb \> 8 g/dL
• Acceptable pulmonary status, including room air O2 saturation \> 90%
• Child-Pugh A-B7 without clinically significant ascites (See Protocol Appendix 4)
• Signed informed consent
• All subjects must be surgically sterile, at least two years post-menopausal (if female), or agree to use adequate, effective contraception approved by the Investigator until two (2) months after receiving a final dose of CSR02-Fab-TF