Intrahepatic Cholangiocarcinoma (Icc)
Conditions
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.
Interventions
DRUGCelecoxib + Pembrolizumab + Gemcitabine/Cisplatin
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.
DRUGPembrolizumab + Gemcitabine/Cisplatin
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.
Sponsors
Shanghai 6th People's Hospital
Shanghai 10th People's Hospital
Wuhan TongJi Hospital
Sun Yat-Sen University Cancer Center
RenJi Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | 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
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 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. |
| Disease Control Rate (DCR) | 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. |
| Overall Survival (OS) | Up to 36 months | Overall survival is defined as the time from randomization to death from any cause. |
| Duration of Response (DoR) | 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. |
| Safety and Tolerability | 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. |
Countries
China
Contacts
CONTACTCun Wang
CONTACTHaiyan Hu
PRINCIPAL_INVESTIGATORCun 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.
Outcome results
None listed