Open-label, Phase II Clinical Study of Chidamide Combined With Chemotherapy and Immunotherapy as First-line Treatment for Advanced Intrahepatic Cholangiocarcinoma
This is a single-center, open-label, phase II clinical trial designed to evaluate the efficacy and safety of chidamide in combination with chemotherapy and immunotherapy as a first-line treatment for patients with advanced intrahepatic cholangiocarcinoma (ICC), a type of liver cancer. The study will enroll approximately 35 patients with histologically or pathologically confirmed unresectable or metastatic ICC who have not received prior systemic therapy. All participants will receive chidamide, an oral HDAC inhibitor, in combination with gemcitabine, cisplatin, and an immune checkpoint inhibitor. Treatment will be administered in 21-day cycles until disease progression, unacceptable toxicity, or other withdrawal criteria are met. The primary study endpoints are objective response rate (ORR), and safety, evaluated by the frequency and severity of adverse events. Secondary endpoints include progression-free survival (PFS), duration of response (DOR), overall survival (OS), and exploratory biomarker analyses. The study aims to assess whether the addition of chidamide to standard chemotherapy and immunotherapy can improve treatment outcomes in this patient population.
• Voluntarily sign the informed consent form (ICF), fully understand the study, and be willing to comply with and capable of completing all trial procedures.
• Male or female, aged 18 to 75 years.
• Patients with histologically or pathologically confirmed unresectable or metastatic intrahepatic cholangiocarcinoma (ICC). Patients with extrahepatic cholangiocarcinoma (EHCC) or gallbladder cancer (GBC) are excluded.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Laboratory test values within 7 days prior to the start of treatment must meet the following criteria:
‣ Neutrophils ≥ 1.5 × 10⁹/L;
⁃ Platelets ≥ 50 × 10⁹/L;
⁃ Hemoglobin ≥ 90 g/L (without packed red blood cell transfusion within the past 2 weeks);
⁃ Serum creatinine ≤ 1.5 × upper limit of normal (ULN) and creatinine clearance ≥ 50 mL/min;
⁃ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN;
⁃ Serum albumin ≥ 30 g/L;
⁃ For patients not receiving anticoagulation therapy: INR or aPTT ≤ 1.5 × ULN. Patients receiving prophylactic anticoagulation are eligible if INR ≤ 2 × ULN and aPTT is within the normal range within 14 days prior to the start of study treatment;
⁃ Serum bilirubin ≤ 1.25 × ULN.
• Life expectancy ≥ 12 weeks.
• Presence of at least one measurable lesion as confirmed by RECIST version 1.1.
• Patients with controlled hepatitis B are eligible if they meet the following criteria: HBV antiviral therapy must have been administered for at least 4 weeks, and HBV viral load must be less than 100 IU/mL prior to the first dose of study drug. Patients receiving anti-HBV treatment with a viral load below 100 IU/mL should maintain the same treatment throughout the study period. Patients who are positive for hepatitis B core antibody (HBcAb), negative for hepatitis B surface antigen (HBsAg), negative or positive for hepatitis B surface antibody (HBsAb), and have an HBV viral load below 100 IU/mL do not require prophylactic anti-HBV treatment.
• Patients must have good compliance.