Efficacy and Safety of Cadonilimab Combined With Gemcitabine and Cisplatin in the First-line Treatment of Unresectable Locally Advanced or Metastatic Biliary Malignancies
The goal of this single-arm, Phase II interventional clinical trial is to test the safety and effectiveness of a combination treatment using the Cadonilimab with Gemcitabine and Cisplatin in patients with unresectable, locally advanced or metastatic biliary tract malignancies. The main questions it aims to answer are: * Is this combined treatment protocol safe for these patients? * Is this combined treatment protocol effective in treating these patients? Participants will be given a combination treatment of Cadonilimab, Gemcitabine, and Cisplatin. Researchers will monitor their health conditions to assess the safety and effectiveness of this treatment protocol.
• Obtain written informed consent before implementing any experimental procedures.
• Age between 18 and 75 years (any gender).
• Histologically or cytologically confirmed unresectable locally advanced or metastatic biliary tumors (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder carcinoma).
• No prior systemic treatment, curative surgery, or adjuvant therapy allowed within the past 6 months.
• Expected survival time \> 3 months.
• Presence of at least one measurable lesion according to RECIST 1.1 criteria.
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-1.
• Adequate organ function, with the following laboratory criteria:
∙ Absolute neutrophil count (ANC) ≥ 1.5x10\^9/L, without the use of granulocyte-colony stimulating factor in the past 14 days.
‣ Platelet count ≥ 90x10\^9/L, without transfusion in the past 14 days.
‣ Hemoglobin \> 9 g/dL, without transfusion or use of erythropoietin-stimulating agents in the past 14 days.
‣ Total bilirubin ≤ 1.5 times the upper limit of normal (ULN).
‣ Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 times ULN (ALT or AST ≤ 5 times ULN for patients with liver metastases).
‣ Serum creatinine ≤ 1.5 times ULN and creatinine clearance (calculated using the Cockcroft-Gault formula) ≥ 60 ml/min.
‣ Coagulation function within normal limits, defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN.
‣ Normal thyroid function, defined as thyroid-stimulating hormone (TSH) within the normal range. If baseline TSH is outside the normal range, subjects with total triiodothyronine (T3) (or free T3) and free thyroxine (FT4) within the normal range can still be included.
‣ Normal cardiac enzymes (clinically insignificant isolated laboratory abnormalities are allowed, as determined by the investigator).
• For premenopausal female subjects, a negative pregnancy test result (urine or serum) should be obtained within 3 days before the first dose of study drug (Day 1 of Cycle 1). If urine pregnancy test results cannot be confirmed as negative, a blood pregnancy test is required. Postmenopausal female is defined as at least 1 year after menopause or having undergone surgical sterilization or hysterectomy.
⁃ If there is a risk of pregnancy, all subjects (both male and female) must use contraception with a failure rate of less than 1% per year throughout the entire treatment period and for 120 days after the last dose of study drug.