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

NCT07632235 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: 2026-086-(1)
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 5

Brief Summary

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 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 endpoint of this study is progression-free survival. Potential treatment-related adverse events associated with chemotherapy, immunotherapy, and celecoxib may include bone marrow suppression, gastrointestinal reactions, immune-related inflammatory responses, and renal or cardiovascular toxicities. The study team will closely monitor participants for adverse events and provide timely and appropriate management as necessary. 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.

Conditions

Intrahepatic Cholangiocarcinoma (Icc)

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Progression-free survival (PFS) is defined as the time from randomization to first documented disease progression per RECIST v1.1 criteria or death from any cause. Disease progression will be assessed by imaging according to RECIST v1.1.

  Up to 24 months

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  Up to 24 months

• Disease Control Rate (DCR)

  Up to 24 months

• Overall Survival (OS)

  Up to 36 months

• Duration of Response (DoR)

  Up to 24 months

• Safety and Tolerability

  From first dose until 30 days after last treatment

Study Arms (2)

Experimental: Celecoxib + Pembrolizumab + Gemcitabine/Cisplatin

EXPERIMENTAL

Participants receive celecoxib in combination with pembrolizumab and gemcitabine plus cisplatin chemotherapy. Celecoxib is administered orally at 200 mg twice daily (BID), starting 7 days before Cycle 1 Day 1 (C1D-7) and continued thereafter. 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 Days 1 and 8 of each 21-day cycle. Cisplatin is administered for a maximum of 8 cycles. Study treatment is continued according to the study protocol until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-specified discontinuation criteria.

Drug: Celecoxib + Pembrolizumab + Gemcitabine/Cisplatin

Active Comparator: Pembrolizumab + Gemcitabine/Cisplatin

ACTIVE COMPARATOR

Participants receive pembrolizumab in combination with gemcitabine plus 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 Days 1 and 8 of each 21-day cycle. Cisplatin is administered for a maximum of 8 cycles. Study treatment is continued according to the study protocol until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-specified discontinuation criteria.

Drug: Pembrolizumab + Gemcitabine/Cisplatin

Interventions

Celecoxib + Pembrolizumab + Gemcitabine/Cisplatin DRUG

Celecoxib is administered orally at 200 mg twice daily (BID), starting 7 days before Cycle 1 Day 1 (C1D-7) in the experimental arm. 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 Days 1 and 8 of each 21-day cycle. Cisplatin is administered for a maximum of 8 cycles. Study treatment is continued according to the study protocol until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-specified discontinuation criteria.

Experimental: Celecoxib + Pembrolizumab + Gemcitabine/Cisplatin

Pembrolizumab + Gemcitabine/Cisplatin DRUG

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 Days 1 and 8 of each 21-day cycle. Cisplatin is administered for a maximum of 8 cycles. Study treatment is continued according to the study protocol until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-specified discontinuation criteria.

Active Comparator: Pembrolizumab + Gemcitabine/Cisplatin

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai 6th People's Hospital: lead
• RenJi Hospital: collaborator
• Shanghai 10th People's Hospital: collaborator
• Wuhan TongJi Hospital: collaborator
• Sun Yat-Sen University Cancer Center: collaborator

Study Sites (5)

Sun Yat-sen University Cancer Center

Guangzhou, China

Location

Renji Hospital

Shanghai, China

Location

Shanghai 10th People's Hospital

Shanghai, China

Location

Shanghai Sixth People's Hospital

Shanghai, China

Location

Wuhan TongJi Hospital

Wuhan, China

Location

MeSH Terms

Conditions

Cholangiocarcinoma; Cirrhosis, Familial, with Pulmonary Hypertension

Interventions

Celecoxib; pembrolizumab; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• 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.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cun Wang

CONTACT

86 18160747569; 18160747569@163.com

Haiyan Hu

CONTACT

xuri1104@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 3, 2026
• First Posted: June 8, 2026
• Study Start: September 15, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030
• Last Updated: August 28, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)