Lenvatinib, Tislelizumab Plus Gemcitabine and Cisplatin (GPLET) in Patients With Advanced Cholangiocarcinoma

Study Overview
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Brief Summary
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Cholangiocarcinoma (CCA) is a heterogeneous group of cancers arising from the epithelial cells of bile ducts. Because of highly aggressive malignancy, most of the patients are diagnosed at an advanced stage and lose the chance to undergo surgery. As more effective and novel chemotherapy, targeted therapies, and immunotherapy become available, multiple treatments can be chosen for the patients with advanced CCA. Cytotoxic cell death during tumor chemotherapy triggers antigen release and induces strong anti-tumor effects of T cells. Tyrosine kinase inhibitors (TKI) can reduce the expression of PD-L1 and inhibit Treg cell infiltration, and together with immune checkpoint inhibitors, they can relieve tumor immunosuppressive microenvironment. Therefore,we aim to investigate the safety and efficacy of lenvatinib, tislelizumab combined with gemcitabine plus cisplatin (GPLET) in the treatment of advanced cholangiocarcinoma.

Official Title
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A Phase Ⅱ, Open Label, Single-center Study of Lenvatinib and Tirelizumab Combined With Gemcitabine and Cisplatin (GPLET) in the Treatment of Advanced Cholangiocarcinoma

Conditions
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Advanced Cholangiocarcinoma

Intervention / Treatment
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* Drug: Lenvatinib, tislelizumab, gemcitabine and cisplatin
* Drug: gemcitabine and cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven, unresectable advanced or metastatic cholangiocarcinoma patients. the world health organization (WHO)/ECOG physical state (PS) to 0 or 1. at least 1 RECIST 1.1 standard target lesions. not previously received immunotherapy, including but not limited to CTLA 4, PD-L1 or/and PD-1 inhibitors. adequate organ and bone marrow function, defined as follows: 9.0 g/dL or higher hemoglobin; neutrophil count 1.5 x 109 / L; platelet count 100 x 109 / L. Exclusion Criteria: Active or previously documented autoimmune disease or inflammatory disease. Uncontrolled complications. History of other primary malignancies. Active infection. Women who are pregnant or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GPLET<br>intravenous gemcitabine 1,000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8; oral lenvatinib 8 mg/day (<60kg) or 12 mg/ d（≥60kg）from days 1 to 21; intravenous tislelizumab 200 mg on day 15 | Drug: Lenvatinib, tislelizumab, gemcitabine and cisplatin<br>* Lenvatinib, tislelizumab, gemcitabine and cisplatin<br>|
| Active Comparator: GP<br>intravenous gemcitabine 1,000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8 | Drug: gemcitabine and cisplatin<br>* gemcitabine and cisplatin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective remission rate (ORR) | According to RECIST v1.1, the proportion of patients with at least one complete response (CR) or partial response (PR) (%) | 4 cycle treatment (each cycle is 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival (PFS) | The time between the date of randomization and the date of radiographic progression as defined by RECIST1.1 | From date of randomization until the date of first documented progression, assessed up to 60 months | 
| Overall survival time (OS) | The time between the date of randomization and death from any cause | From date of randomization until the date of death from any cause, assessed up to 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lenvatinib; Gemcitabine and Cisplatin; Tislelizumab; Cholangiocarcinoma