A Multicenter, Prospective, Randomized, Open-label Phase Ib/II Study of Celecoxib Plus Pembrolizumab and Gemcitabine/Cisplatin Versus Pembrolizumab and Gemcitabine/Cisplatin in Patients With CK5/6-High Unresectable Locally Advanced or Metastatic Intrahepatic Cholangiocarcinoma

This study aims to evaluate whether adding celecoxib to standard therapy can improve clinical outcomes in patients with advanced intrahepatic cholangiocarcinoma. The current standard treatment typically consists of immunotherapy combined with chemotherapy; however, there are significant inter-patient differences in treatment response. Therefore, this study further introduces the biomarker CK5/6 to identify patient subgroups who are more likely to benefit, thereby exploring a more precise therapeutic strategy.

All eligible participants will be randomly assigned after enrollment to either the control group or the experimental group. The control group will receive the current standard first-line regimen, which includes the immunotherapy agent pembrolizumab combined with the chemotherapy agents gemcitabine and cisplatin. The experimental group will receive the same standard treatment, with the addition of oral anti-inflammatory therapy with celecoxib taken twice daily throughout the entire treatment period.

Each treatment cycle lasts 21 days. During treatment, patients will undergo regular imaging assessments, laboratory tests, and safety evaluations to monitor tumor response and treatment-related adverse events, and will be followed until disease progression or discontinuation of treatment. In addition, blood and tissue samples will be collected during the study to investigate tumor biology and potential predictive biomarkers.

The primary endpoints of this study include progression-free survival and objective response rate, along with concurrent safety evaluation. Adverse events potentially associated with chemotherapy, immunotherapy, and celecoxib may occur, such as bone marrow suppression, gastrointestinal reactions, immune-related inflammatory responses, as well as renal or cardiovascular toxicities. The study team will closely monitor and promptly manage all adverse events.

This study aims to explore a CK5/6-based stratified personalized combination therapy strategy, with the goal of improving treatment benefit in patients with advanced intrahepatic cholangiocarcinoma and providing evidence for optimizing future clinical treatment strategies.

Study Overview

• Status: Not yet recruiting
• Conditions: Intrahepatic Cholangiocarcinoma (Icc)
• Intervention / Treatment: Drug: Celecoxib + Pembrolizumab + Gemcitabine/Cisplatin; Drug: Pembrolizumab + Gemcitabine/Cisplatin

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: chen yang; Phone Number: 86 18160747569; Email: 18160747569@163.com
• Study Contact Backup: Name: haiyan hu; Email: xuri1104@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 years.
• Histologically or cytologically confirmed intrahepatic cholangiocarcinoma (iCCA).
• Unresectable locally advanced, recurrent, or metastatic disease.
• No prior systemic therapy for advanced disease.
• At least one measurable lesion according to RECIST v1.1.
• ECOG performance status of 0-1.
• Availability of adequate pre-treatment tumor tissue for central pathological review.
• CK5/6 H-score ≥ 1.0 as determined by central laboratory testing.
• Adequate organ and bone marrow function as defined by protocol-specified laboratory criteria.
• Patients with biliary obstruction must have undergone effective drainage and achieved clinical stabilization prior to enrollment.
• Ability to provide written informed consent.

Exclusion Criteria:

• Other primary malignancies including extrahepatic cholangiocarcinoma, gallbladder carcinoma, or ampullary carcinoma.
• CK5/6 H-score < 1.0.
• Prior systemic therapy for advanced or metastatic disease.
• Active gastrointestinal bleeding, peptic ulcer disease, or high risk of gastrointestinal perforation.
• Recent history of significant cardiovascular events including myocardial infarction, stroke, uncontrolled hypertension, or severe heart failure.
• Known hypersensitivity to celecoxib, sulfonamides, NSAIDs, or aspirin-exacerbated respiratory disease.
• Active autoimmune disease or conditions contraindicating pembrolizumab therapy.
• Severe renal impairment.
• Child-Pugh class C hepatic impairment.
• Active uncontrolled infection.
• Any condition that, in the investigator's opinion, would interfere with study participation or interpretation of results.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Celecoxib + Pembrolizumab + Gemcitabine/Cisplatin; Participants receive celecoxib in combination with pembrolizumab and gemcitabine/cisplatin chemotherapy. Celecoxib is administered orally at 200 mg twice daily continuously starting from Cycle 1 Day -7. Pembrolizumab is administered intravenously at 200 mg on Day 1 of each 21-day cycle. Gemcitabine (1000 mg/m²) and cisplatin (25 mg/m²) are administered intravenously on Day 1 and Day 8 of each cycle. Cisplatin is given for up to 8 cycles. Treatment is continued until disease progression, unacceptable toxicity, or withdrawal.	Drug: Celecoxib + Pembrolizumab + Gemcitabine/Cisplatin; Celecoxib is administered orally at a dose of 200 mg twice daily continuously in the experimental arm. Treatment is initiated at Cycle 1 Day -7 and continued until disease progression, unacceptable toxicity, or withdrawal.
Active Comparator: Active Comparator: Pembrolizumab + Gemcitabine/Cisplatin; Participants receive pembrolizumab in combination with gemcitabine/cisplatin chemotherapy. Pembrolizumab is administered intravenously at 200 mg on Day 1 of each 21-day cycle. Gemcitabine (1000 mg/m²) and cisplatin (25 mg/m²) are administered intravenously on Day 1 and Day 8 of each cycle. Cisplatin is given for up to 8 cycles. Treatment is continued until disease progression, unacceptable toxicity, or withdrawal.	Drug: Pembrolizumab + Gemcitabine/Cisplatin; Participants receive pembrolizumab 200 mg intravenously on Day 1 of each 21-day cycle in combination with gemcitabine 1000 mg/m² and cisplatin 25 mg/m² administered intravenously on Days 1 and 8 of each cycle. Cisplatin is administered for up to 8 cycles. Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	Progression-free survival (PFS) is defined as the time from randomization to the first documented disease progression per RECIST v1.1 criteria or death from any cause, whichever occurs first. Disease progression will be assessed by imaging review according to RECIST v1.1 in both treatment arms.	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective response rate (ORR) is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) as assessed by investigators according to RECIST v1.1 criteria in both treatment arms.	Up to 24 months
Disease Control Rate (DCR)	Disease control rate is defined as the proportion of participants achieving complete response, partial response, or stable disease according to RECIST v1.1 criteria.	Up to 24 months
Overall Survival (OS)	Overall survival is defined as the time from randomization to death from any cause.	Up to 36 months
Duration of Response (DoR)	Duration of response is defined as the time from first documented objective response (CR or PR) to disease progression or death.	Up to 24 months
Safety and Tolerability	Safety and tolerability will be assessed by incidence, severity, and type of adverse events graded according to CTCAE v5.0.	From first dose until 30 days after last treatment

Collaborators and Investigators

• Sponsor: Shanghai 6th People's Hospital
• Collaborators: RenJi Hospital; Shanghai 10th People's Hospital; Wuhan TongJi Hospital; Sun Yat-Sen University Cancer Center
• Investigators: Principal Investigator: cun wang, State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute & Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: June 3, 2026
• First Submitted That Met QC Criteria: June 3, 2026
• First Posted (Actual): June 8, 2026

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Cholangiocarcinoma; Cirrhosis, Familial, with Pulmonary Hypertension; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Amides; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Benzene Derivatives; Platinum Compounds; Benzenesulfonamides; Sulfonamides; Sulfones; Pyrazoles; Celecoxib; Gemcitabine; Cisplatin; pembrolizumab
• Other Study ID Numbers: 2026-086-(1)

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