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

NCT06903273 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: NCKUH-BTC-01
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Cholangiocarcinoma; Biliary Tract Cancer (BTC)

Keywords

cholangiocarcinoma; biliary tract cancer; neoadjuvant; gemcitabine; S-1; preoperative; resectable; tislelizumab; cisplatin

Outcome Measures

Primary Outcomes (1)

• R0 resection rate

  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 Outcomes (4)

• Objective response rate

  From enrollment to the end of neoadjuvant therapy at 2 weeks

• Overall survival

  From the date of enrollment until the date of death from any cause

• Event-free survival

  From the date of enrollment until the date of any predefined event which happens first

• Disease control rate

  From enrollment to the end of neoadjuvant therapy at 2 weeks

Other Outcomes (2)

• Protocol completion rate

  From enrollment to the end of neoadjuvant therapy at 2 weeks

• Adverse events related to protocol treatment

  From enrollment to the end of neoadjuvant therapy at 2 weeks

Study Arms (1)

Tislelizumab-Gemcitabine/Cisplatin/S-1

EXPERIMENTAL

neoadjuvant tislelizumab/gemcitabine/cisplatin/S-1

Drug: Tislelizumab

Interventions

Tislelizumab DRUG

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)

Also known as: gemcitabine, cisplatin, S-1

Tislelizumab-Gemcitabine/Cisplatin/S-1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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 \&gt;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.

You may not qualify if:

• Subjects have metastatic (M1) disease, recurrent cholangiocarcinoma which cannot be resected, recurrent cholangiocarcinoma which can be re-resected but occurs \&gt;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 are known to be severely allergic to any of the studied therapeutics.
• 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.
• 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.
• \. 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).
• \. 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.

Sponsors & Collaborators

• National Cheng-Kung University Hospital: lead
• Kaohsiung Veterans General Hospital.: collaborator
• Chi Mei Medical Hospital: collaborator

Study Sites (1)

National Cheng Kung University Hospital

Tainan, 70403, Taiwan

Location

Related Publications (4)

• Maithel SK, Keilson JM, Cao HST, Rupji M, Mahipal A, Lin BS, Javle MM, Cleary SP, Akce M, Switchenko JM, Rocha FG. NEO-GAP: A Single-Arm, Phase II Feasibility Trial of Neoadjuvant Gemcitabine, Cisplatin, and Nab-Paclitaxel for Resectable, High-Risk Intrahepatic Cholangiocarcinoma. Ann Surg Oncol. 2023 Oct;30(11):6558-6566. doi: 10.1245/s10434-023-13809-5. Epub 2023 Jun 27.

  PMID: 37368098 BACKGROUND

• Oh DY, Ruth He A, Qin S, Chen LT, Okusaka T, Vogel A, Kim JW, Suksombooncharoen T, Ah Lee M, Kitano M, Burris H, Bouattour M, Tanasanvimon S, McNamara MG, Zaucha R, Avallone A, Tan B, Cundom J, Lee CK, Takahashi H, Ikeda M, Chen JS, Wang J, Makowsky M, Rokutanda N, He P, Kurland JF, Cohen G, Valle JW. Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer. NEJM Evid. 2022 Aug;1(8):EVIDoa2200015. doi: 10.1056/EVIDoa2200015. Epub 2022 Jun 1.

  PMID: 38319896 BACKGROUND

• Kelley RK, Ueno M, Yoo C, Finn RS, Furuse J, Ren Z, Yau T, Klumpen HJ, Chan SL, Ozaka M, Verslype C, Bouattour M, Park JO, Barajas O, Pelzer U, Valle JW, Yu L, Malhotra U, Siegel AB, Edeline J, Vogel A; KEYNOTE-966 Investigators. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 Jun 3;401(10391):1853-1865. doi: 10.1016/S0140-6736(23)00727-4. Epub 2023 Apr 16.

  PMID: 37075781 BACKGROUND

• Ioka T, Kanai M, Kobayashi S, Sakai D, Eguchi H, Baba H, Seo S, Taketomi A, Takayama T, Yamaue H, Takahashi M, Sho M, Kamei K, Fujimoto J, Toyoda M, Shimizu J, Goto T, Shindo Y, Yoshimura K, Hatano E, Nagano H; Kansai Hepatobiliary Oncology Group (KHBO). Randomized phase III study of gemcitabine, cisplatin plus S-1 versus gemcitabine, cisplatin for advanced biliary tract cancer (KHBO1401- MITSUBA). J Hepatobiliary Pancreat Sci. 2023 Jan;30(1):102-110. doi: 10.1002/jhbp.1219. Epub 2022 Aug 9.

  PMID: 35900311 BACKGROUND

MeSH Terms

Conditions

Cholangiocarcinoma; Biliary Tract Neoplasms

Interventions

tislelizumab; Gemcitabine; Cisplatin; S 1 (combination)

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Chia Jui Yen, MD., PhD

  Department on Oncology, National Cheng Kung University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trial Center, National Cheng Kung University Hospital

CONTACT

886-6-2353535; ctcnckuh@mail.hosp.ncku.edu.tw

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Simon two-staged design

Study Record Dates

• First Submitted: March 18, 2025
• First Posted: March 30, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2029
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 01/Jul/2025 to 01/Jul/2028
• Access Criteria: Reviewers with a reasonable request to the principal investigator, Dr. Chih Jui, YEN.

Locations

TW (1)