Neoadjuvant Tislelizumab, Gemcitabine, Cisplatin and S-1 for Resectable High-risk Cholangiocarcinoma (TisGCS for BTC)

March 24, 2025 updated by: Chih Chieh, Yen, National Cheng-Kung University Hospital

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

To investigate the efficacy and tolerability of neoadjuvant tislelizumab, gemcitabine, cisplatin and S-1 (TisGCS) in patients with resectable high-risk iCCA.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Patients with cholangiocarcinoma have limited therapeutic options and a poor prognosis. Margin-free resection is the only curative treatment to treat intrahepatic cholangiocarcinoma (iCCA). However, patients with resectable disease still suffer from high recurrence or progression. Both immune checkpoint inhibitors and chemotherapy have shed light on treating patients with iCCA. Nevertheless, the role of neoadjuvant chemo-immunotherapy has not been established in patients with resectable iCCA harboring a high risk for recurrence. The aim of the trial is to investigate the efficacy and tolerability of neoadjuvant tislelizumab, gemcitabine, cisplatin and S-1 (Tis-GCS) in patients with resectable high-risk iCCA. The primary outcome is R0 resection rate. The secondary outcome includes objective response rate, event-free survival, overall survival, protocol completion rate and adverse events. The study is an open-label, single-arm and multi-center phase II investigator-initiated trial with Simon two-stage design. Subjects with resectable iCCA harboring a high risk for recurrence or those suffer from very early recurrent disease who are eligible for a curative resection are included. A total of 35 subjects are expected with a minimal sample size of 14 when the R0 resection rate is of the lower threshold. Tis-GCS (14 days as a cycle) 3 cycles every 2 weeks will be administered and followed by surgery. Tislelizumab 200 mg fixed-dose, gemcitabine 800 mg/m2 and cisplatin 25 mg/m2 is given intravenously on day 1. S-1 (35 mg/m2) is given twice daily per oral on day 1 to 7. The study will prove the feasibility and efficacy of neoadjuvant chemo-immunotherapy in resectable high-risk iCCA. The results may provide critical fundamentals into future phase III clinical trials.

Study Type

Interventional

Enrollment (Estimated)

35

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Taiwan
      • Tainan, Taiwan, 70403
        • National Cheng Kung University Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

- 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,

  1. Solitary tumor with a maximal diameter ≥5 cm in the absence of vascular invasion.
  2. ≥T1b disease which is resectable.
  3. Multifocal tumors or single tumor with satellite nodules at the same anatomic liver lobe which is/are resectable.
  4. Tumor(s) with macroscopic intrahepatic vascular invasion but is/are potentially resectable.
  5. Image or histological evidence of hilar or portal lymph node involvement (N1).

  6. 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.

    1. 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).
    2. 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
    3. 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.
    4. Subjects have or agree to establish a vascular access that permits intravenous administration of medications and are capable of ingesting capsules per oral.
    5. Subjects with reproductive potentials are willing to accept contraceptive measures during the trial.
    6. 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.

    Exclusion Criteria:

    1. 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.
    2. 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.
    3. Subjects are known to be severely allergic to any of the studied therapeutics.
    4. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tislelizumab-Gemcitabine/Cisplatin/S-1
neoadjuvant tislelizumab/gemcitabine/cisplatin/S-1
Drug: Tislelizumab

Tislelizumab plus chemotherapy (14 days as one cycle) 3 cycles every 2 weeks as neoadjuvant therapy and followed by a curative surgery.

Tislelizumab 200 mg fixed-dose IVD on day 1. Gemcitabine 800 mg/m2 on day 1 with a fixed-infusion rate of 80 mins. Cisplatin 25 mg/m2 on day 1. S-1 70 mg/m2 daily as a BID dosing per oral on day 1 to 7. (daily total dose determined by body surface area (BSA): <1.25 m2, 80 mg; 1.25-1.50 m2, 100 mg; ≥1.50 m2, 120 mg)

Other Names:
  • gemcitabine
  • cisplatin
  • S-1

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
R0 resection rate
Time Frame: From enrollment to surgical resection at 2 weeks
Margin-free resection (R0) rate: (Number of patients with surgical results achieving an uninvolved margin under microscopic and macroscopic inspection) / (Number of patients receiving a surgery) x 100%
From enrollment to surgical resection at 2 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate
Time Frame: From enrollment to the end of neoadjuvant therapy at 2 weeks
Patients who achieve a complete or partial response as defined by revised Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
From enrollment to the end of neoadjuvant therapy at 2 weeks
Overall survival
Time Frame: From the date of enrollment until the date of death from any cause
The time interval from enrollment to death by any causes
From the date of enrollment until the date of death from any cause
Event-free survival
Time Frame: From the date of enrollment until the date of any predefined event which happens first
The time interval from enrollment to an event, defined as disease progression, recurrence, withdrawal from trial treatment, initiation of subsequent anticancer treatment or death by any cause, in whichever happens first.
From the date of enrollment until the date of any predefined event which happens first
Disease control rate
Time Frame: From enrollment to the end of neoadjuvant therapy at 2 weeks
Patients who achieve a complete response, partial response or stable disease, as defined by revised Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
From enrollment to the end of neoadjuvant therapy at 2 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Protocol completion rate
Time Frame: From enrollment to the end of neoadjuvant therapy at 2 weeks
Patients who complete the protocol neoadjuvant treatment / Enrolled patients X100%
From enrollment to the end of neoadjuvant therapy at 2 weeks
Adverse events related to protocol treatment
Time Frame: From enrollment to the end of neoadjuvant therapy at 2 weeks
Patients who present with ≥grade III adverse events resulting from protocol treatment per National Cancer Institute- Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE 5.0).
From enrollment to the end of neoadjuvant therapy at 2 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cheng-Kung University Hospital

Collaborators

Kaohsiung Veterans General Hospital.
Chi Mei Medical Hospital

Investigators

  • Principal Investigator: Chia Jui Yen, MD., PhD, Department on Oncology, National Cheng Kung University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2025

Primary Completion (Estimated)

July 1, 2028

Study Completion (Estimated)

July 1, 2029

Study Registration Dates

First Submitted

March 18, 2025

First Submitted That Met QC Criteria

March 24, 2025

First Posted (Actual)

March 30, 2025

Study Record Updates

Last Update Posted (Actual)

March 30, 2025

Last Update Submitted That Met QC Criteria

March 24, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCKUH-BTC-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

study protocol

IPD Sharing Time Frame

01/Jul/2025 to 01/Jul/2028

IPD Sharing Access Criteria

Reviewers with a reasonable request to the principal investigator, Dr. Chih Jui, YEN.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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