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NCT Number: NCT07632235

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 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.

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Key information

Conditions

Intrahepatic Cholangiocarcinoma (Icc) Adenocarcinoma Carcinoma Cholangiocarcinoma Cirrhosis, Familial, with Pulmonary Hypertension Neoplasms Neoplasms by Histologic Type Neoplasms, Glandular and Epithelial

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Sun Yat-sen University Cancer Center, Guangzhou, China

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

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.

Primary outcomes

  1. Progression-Free Survival (PFS)

    Time frame: Up to 24 months

    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.

Secondary outcomes

  1. Objective Response Rate (ORR)

    Time frame: Up to 24 months

    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.

  2. Disease Control Rate (DCR)

    Time frame: Up to 24 months

    Disease control rate is defined as the proportion of participants achieving complete response, partial response, or stable disease according to RECIST v1.1 criteria.

  3. Overall Survival (OS)

    Time frame: Up to 36 months

    Overall survival is defined as the time from randomization to death from any cause.

  4. Duration of Response (DoR)

    Time frame: Up to 24 months

    Duration of response is defined as the time from first documented objective response (CR or PR) to disease progression or death.

  5. Safety and Tolerability

    Time frame: From first dose until 30 days after last treatment

    Safety and tolerability will be assessed by incidence, severity, and type of adverse events graded according to CTCAE v5.0.

Study contacts

Contact information is provided by the study sponsor or research team.

Cun Wang

CONTACT

[email protected]

86 18160747569

Haiyan Hu

CONTACT

[email protected]

Sponsors and collaborators

Lead sponsor

Shanghai 6th People's Hospital

Other

Collaborators

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

Registry information

Important dates

Study start
2026
Primary completion
2029
Study completion
2030
First posted
Jun 8, 2026
Registry last updated
Aug 28, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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