A Phase 2, Open-label, Single Arm Study of Combined HAIC, Lenvatinib and Pucotenlimab As Conversion Therapy for Unresectable Intrahepatic Cholangiocarcinoma
This is an open-label, single-arm, phase 2 study. The purpose of study is to evaluate the feasibility and safety of hepatic artery infusion chemotherapy combined with lenvatinib and pucotenlimab as conversion therapy for unresectable intrahepatic cholangiocarcinoma.
• Histologically confirmed intrahepatic cholangiocarcinoma.
• Age ≥18 years.
• ECOG performance status score of 0 or 1.
• Not suitable for radical surgery (including radical hepatic resection, liver transplantation or ablation) after evaluation by the MDT expert group of treating hepatobiliary cancer. Specifically, any of the following conditions are met：
‣ R0 resection is not feasible.
⁃ in subjects without cirrhosis, the volume of normal liver parenchyma is less than 30% of the total volume, or in patients with cirrhosis, the volume of normal liver parenchyma is less than 40% of the total volume, or ICG-R15\>15%.
⁃ Number of lesions \>1.
• No prior systemic anti-tumor treatment for intrahepatic cholangiocarcinoma before the first dose.
• According to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1), at least 1 measurable lesion, or a measurable lesion that has clearly progressed (based on RECIST V1.1 criteria) after local treatment.
• Subjects with portal vein tumor thrombus (PVTT):
‣ Chen's group A and B, or Cheng's type I-III can be enrolled.
⁃ Chen's group C, or Cheng's type IV (superior vena cava tumor thrombus) cannot be enrolled.
• Subjects with hepatic vein tumor thrombus:
‣ VV1 and VV2 types can be enrolled.
⁃ VV3 type, or Sakamoto type I (inferior vena cava tumor thrombus) can also be enrolled.
⁃ Sakamoto type II (inferior vena cava tumor thrombus extending above the diaphragm), or Sakamoto type III (inferior vena cava tumor thrombus reaching the right atrium) cannot be enrolled.
• Subjects with oligometastases outside the liver can be enrolled: Oligometastases outside the liver are defined as up to three metastatic lesions in a maximum of two organs, with the largest diameter being 3cm.
• Child-Pugh score less than or equal to 7.
• Adequate organ and bone marrow function, with laboratory test values meeting the following requirements within 7 days prior to inclusion (no blood components, cell growth factors, albumin, or other intravenous or subcutaneous corrective treatment drugs are allowed within 14 days prior to obtaining laboratory tests):
‣ Complete blood count: Absolute Neutrophil Count (ANC) ≥1.5×10\^9/L; Platelet count (PLT) ≥75×10\^9/L; Hemoglobin (HGB) ≥9.0 g/dL.
⁃ Liver function: Total Bilirubin (TBIL) ≤2×Upper Limit of Normal Value (ULN); Alanine Aminotransferase (ALT) and Aspartate Transferase (AST) ≤5×ULN; Serum albumin ≥28 g/L; Alkaline Phosphatase (ALP) ≤5×ULN.
⁃ Kidney function: Serum Creatinine (Cr) ≤ 1.5×ULN or Clearance of Creatinine (CCr) ≥50mL/min (Cockcroft-Gault formula); Urinalysis shows proteinuria \<2+; For subjects with baseline urinalysis showing proteinuria ≥2+, a 24-hour urine collection should be performed and 24-hour urinary protein quantification \<1g.
⁃ Coagulation function: International Normalized Ratio (INR) ≤2.3 or Prothrombin Time (PT) extension ≤6 seconds.
• Estimated life expectancy of ≥12 weeks.
• Female subjects of childbearing age or male subjects whose sexual partners are of childbearing age need to take effective contraceptive measures during the entire treatment period and for 6 months after the last medication.
• Signed written informed consent, and able to comply with the visit and related procedures stipulated in the protocol.