Neoadjuvant Tislelizumab, Gemcitabine, Cisplatin and S-1 for Resectable High-risk Cholangiocarcinoma

Prior treatment

• Subjects have metastatic (M1) disease, recurrent cholangiocarcinoma which cannot be resected, recurrent cholangiocarcinoma which can be re-resected but occurs \>6 months post previous surgery, or any other primary malignancies in which the subjects have been in disease-free status less than 2 years, excluding carcinoma in situ or resectable skin cancer.
• Subjects have received a systemic therapy with either chemotherapeutics or immune checkpoint inhibitors, a major abdominal surgery or radiotherapy within 4 weeks before the trial enrollment.
• Subjects have underlying chronic illnesses, including cardiopulmonary diseases, ischemic heart disease, inflammatory bowel disease, poorly-controlled diabetes mellitus, liver cirrhosis and/or debilitating autoimmune diseases or conditions.
  • 5 Subjects are receiving or have received a systemic administration of an equivalent dose of daily 10 mg prednisone or above for ≥14 days in whatever indications within 4 weeks before the trial enrollment, or immunosuppressives for ≥7 days within 4 weeks before the trial enrollment.
  • 6\. Subjects have active bacterial, viral, fungal or mycobacterial infections that require systemic therapy, including active infection with human immunodeficiency virus (HIV), hepatitis B or C virus (HBV or HCV).
  • 7\. Subjects are planning to conceive or already in pregnancy or breastfeeding. 8. Subjects are currently participating in any other clinical trials or studies which potentially interfere the protocol commencement.

Other illness

• Subjects are known to be severely allergic to any of the studied therapeutics.

• \- Subjects must meet the criteria of either (A) or (B), plus 1. to 6. (A) High-risk group (HR) Subjects have histologically-confirmed and potentially resectable intrahepatic cholangiocarcinoma, according to the definition of American Joint Cancer Committee staging system, 8th edition (AJCC 8th).
• Plus at least one of the following high-risk features,
• Solitary tumor with a maximal diameter ≥5 cm in the absence of vascular invasion.
• ≥T1b disease which is resectable.
• Multifocal tumors or single tumor with satellite nodules at the same anatomic liver lobe which is/are resectable.
• Tumor(s) with macroscopic intrahepatic vascular invasion but is/are potentially resectable.
• Image or histological evidence of hilar or portal lymph node involvement (N1).
• Initial serum cancer antigen-199 (CA199) ≥200 U/mL.
  • (B) Very early recurrence group (VER) Subjects with previously resected cholangiocarcinoma under a curative intent and have an early recurrent disease (≤6 months post curative surgery) confined to the liver, with/without antecedent adjuvant local or systemic therapies, and can be re-resected under a curative intent.
  • Subjects present with at least one measurable lesion which can be accurately assessed by conventional techniques at least 1.0 cm by computed tomography (CT) or magnetic resonance imaging (MRI).
  • Subjects are above 18 years of age with an Eastern Cooperative Oncology Group (ECOG) performance status ≤1, have a life expectancy \>3 months, have surgically resectable disease and are physically competent and willing to receive a curative operation following the study protocol
  • Subjects have adequate organ functions, including bone marrow reserve with a leukocyte count ≥3,000 /µL and platelet count ≥50,000 /µL, hepatic reserve with a serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin ≤3 times of upper normal testing limits (biliary drainage is permitted), renal reserve with a creatinine clearance ≥60 mL/min and cardiac reserve with a New York Heart Association (NYHA) functional classification I at baseline.
  • Subjects have or agree to establish a vascular access that permits intravenous administration of medications and are capable of ingesting capsules per oral.
  • Subjects with reproductive potentials are willing to accept contraceptive measures during the trial.
  • Subjects are functionally and cognitively capable to be informed of the trial contents and objectives (including obtaining blood and tumor tissue for the trial investigation), and agree to sign the written consent for enrollment.