Advanced Cholangiocarcinoma
Conditions
Keywords
Lenvatinib, Tislelizumab, Gemcitabine and Cisplatin
Brief summary
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, the study aims to investigate the safety and efficacy of Lenvatinib, Tislelizumab combined with Gemcitabine plus Cisplatin (GPLET) in the treatment of advanced cholangiocarcinoma.
Interventions
Intravenous injection: gemcitabine and cisplatin (CG) + tislelizumab； Oral administration: lenvatinib.
DRUGGemcitabine and cisplatin
Intravenous injection: gemcitabine and cisplatin (CG) + placebo； Oral administration: placebo.
Sponsors
The First Affiliated Hospital of Zhengzhou University
The Affiliated Tumor Hospital of Xinjiang Medical University
Second Affiliated Hospital, School of Medicine, Zhejiang University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Histologically proven, unresectable advanced or metastatic cholangiocarcinoma patients. * Expected survival period \> 12 weeks. * The World Health Organization (WHO) / ECOG physical status (PS) was 0 or 1. * There was at least one target lesion that matched the RECIST 1.1 criteria at baseline. * 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: Hemoglobin (Hb)≥9.0g/dL; Neutrophils (ANC) ≥ 1.5\* 10\^9/L; Platelet (Pt) ≥ 50\*10\^9/L; ALT≤2.5×ULN（Normal upper limit); AST≤2.5×ULN. * Voluntary participation and signing of informed consent.
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. * Patients with severe allergic history or specific constitution. * Researchers consider it inappropriate to participate in the test.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective remission rate (ORR) | At the end of 4 treatment cycles(each cycle is 21 days) | The proportion of patients with at least one complete response (CR) or partial response (PR) (%) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | From date of randomization until the date of first documented progression, assessed up to 60 months | The time between the date of randomization and the date of radiographic progression |
| Overall survival time (OS) | From date of randomization until the date of death from any cause, assessed up to 60 months | The time between the date of randomization and death from any cause |
Countries
China
Contacts
Primary ContactWeilin Wang, doctor
Outcome results
None listed