Exploring the Efficacy and Safety of Tislelizumab in Combination With S-1 in the Treatment of Patients With Postoperative Recurrent High-risk Intrahepatic Cholangiocarcinoma

Exploring the Efficacy and Safety of Tislelizumab in Combination With S-1 in the Treatment of Patients With Postoperative Recurrent High-risk Intrahepatic Cholangiocarcinoma：A Prospective, Multicenter, Phase II Clinical Study

Evaluating the efficacy and safety of treatment with Tislelizumab in combination with S-1 in patients with high-risk recurrent intrahepatic cholangiocarcinoma after radical surgery

Study Overview

• Status: Recruiting
• Conditions: Intrahepatic Cholangiocarcinoma
• Intervention / Treatment: Drug: Tislelizumab combined with S-1

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ji-Zhou Wang; Phone Number: +86 13836135864; Email: wangjoe@ustc.edu.cn

Study Locations

• China
  • Anhui
    • Fuyang, Anhui, China, 236015
      • Recruiting
      • NO.2 People's Hospital of Fuyang City
      • Contact: DaYong Luo; Phone Number: 13805587172; Email: fyldy7172@sina.com
    • Hefei, Anhui, China, 230000
      • Recruiting
      • Anhui Province Hospital
      • Contact: Ji-Zhou Wang, M.D.; Phone Number: +86 13836135864; Email: wangjoe@ustc.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18-75 years old, male and female;
• Intrahepatic cholangiocarcinoma was pathologically confirmed after R0 or R1 resection. Patients were also pathologically confirmed to have one of the following high-risk factors (i.e., positive margins, multiple tumor nodes, positive lymph nodes, positive perineural infiltration, intrahepatic cholangiocarcinoma >5 cm in diameter, and combined vascular invasion);
• Enhanced computed tomography (CT) scans of the chest, abdomen, and pelvis were required within 30 days prior to surgery to demonstrate the absence of distant tumor metastases;
• No history of any chemotherapy, radiotherapy, immunotherapy or interventional therapy within 3 months prior to surgical resection;
• Child-Pugh grade A or B, ECOG score 0-1;
• Normal organ function prior to drug administration: ANC ≥1.5×10^9/L, Hemoglobin ≥90g/L, PLT >50*10^9/L, serum creatinine (SCr) ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance ≥50 ml/min (Cockcroft-Gault formula); total bilirubin (TBIL) ≤2 times the upper limit of normal (ULN); glutamine transaminase (AST) or glutamine transaminase (ALT) levels ≤3 times the ULN; urinary protein <2+ (if urinary protein) upper limit of normal (ULN); albumin transaminase (AST) or alanine transaminase (ALT) levels ≤3 times upper limit of normal (ULN); urine protein <2+ (if urine protein ≥2+, 24-hour urine protein quantification must show ≤1g of protein); and adequate surgical biliary drainage with no signs of infection.
• Normal coagulation function: a. International normalized ratio INR ≤ 1.5 x ULN; b. Partial thromboplastin time APTT ≤ 1.5 x ULN; c. Prothrombin time PT ≤ 1.5 ULN;
• In case of hepatitis B virus (HBV) infection: if HBsAg-positive, HBV-DNA testing is required and HBV-DNA must be <2000 IU/mL and willing to receive antiviral therapy throughout the study period; hepatitis C virus (HCV)-RNA-positive patients must have HCV-RNA <1×10^3copy/mL and must receive antiviral therapy according to treatment guidelines.
• No major abnormalities in heart, lung or kidney function;
• No history of gastrointestinal hemorrhage;
• Sign the informed consent form.

Exclusion Criteria:

• The tumor is not completely resected, or the pathological diagnosis suggests non-intrahepatic cholangiocarcinoma such as hepatocellular carcinoma, mixed hepatocellular carcinoma, and hepatoportal cholangiocarcinoma;
• Pregnant or breastfeeding women;
• Combined with other malignant tumors;
• Have any active autoimmune disease or a history of autoimmune disease;
• Uncontrolled clinically significant cardiac disease, including but not limited to the following: (1) > NYHA II congestive heart failure; (2) unstable angina pectoris; (3) myocardial infarction within the last 1 year; (4) clinically significant supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention;
• The patient has a congenital or acquired immunodeficiency;
• Uncontrollable infection > grade 2 (NCI-CTC version 5.0);
• Psychopaths;
• Patients have participated in other clinical trials within the past three months;
• Postoperative patients receiving other targeted agents, immunotherapy such as PD-1 antibodies, and FOLFOX systemic chemotherapy;
• Patients who are not suitable to participate in the study as determined by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group; Tislelizumab + S-1	Drug: Tislelizumab combined with S-1; Tislelizumab：200mg q3w iv , lasts for one year. S-1：40mg, 50mg, or 60mg orally twice daily for 4 weeks, depending on body surface area, followed by 2 weeks of rest，lasts four cycles.
No Intervention: No treatment group; No postoperative adjuvant therapy is performed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year RFS rate	Proportion of patients with no local, regional, or metastatic ICC or death from any cause (whichever occurs first) 12 months after hepatectomy.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RFS	Time from hepatectomy to the first documented occurrence of local, regional, or metastatic ICC or death from any cause, whichever occurs first.	24 months
OS	Time from hepatectomy to first recorded occurrence of death from any cause	24 months
Survival time after recurrence	The time from the first documented occurrence of localized, regional, or metastatic ICC, whichever occurs first, to death from any cause.	24 months
AEs AEs AEs AEs AE	Adverse Events (AEs)The grade of AEs and the number of patients with AEs are assessed based on CTCAE v5.0	24 months

Collaborators and Investigators

• Sponsor: Anhui Provincial Hospital
• Investigators: Principal Investigator: Lian-xin Liu, Anhui Provincial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: October 27, 2024
• First Submitted That Met QC Criteria: October 27, 2024
• First Posted (Actual): October 29, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 9, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Cholangiocarcinoma; Antineoplastic Agents, Immunological; Antineoplastic Agents; Tislelizumab
• Other Study ID Numbers: 2024KY467

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No