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

Phase 2

Recruiting

• Conditions: Advanced Cholangiocarcinoma
• Interventions: Drug: Lenvatinib, tislelizumab, gemcitabine and cisplatin; Drug: gemcitabine and cisplatin

• Registration Number: NCT05532059
• Lead Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

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,we aim to investigate the safety and efficacy of lenvatinib, tislelizumab combined with gemcitabine plus cisplatin (GPLET) in the treatment of advanced cholangiocarcinoma.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-01-31
• Study First Submitted: 2022-08-22
• Study First Submitted QC: 2022-09-05
• Study First Posted: 2022-09-08
• Status Verified: 2025-01
• Last Update Submitted: 2025-02-05
• Last Update Posted: 2025-02-10
• Primary Completion: 2025-08-31
• Study Completion: 2028-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GPLET	Lenvatinib, tislelizumab, gemcitabine and cisplatin	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
GP	gemcitabine and cisplatin	intravenous gemcitabine 1,000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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 as defined by RECIST1.1
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

Trial Locations

Locations (1)

The Second Affiliated Hospital, Zhejiang University School of Medicine; 🇨🇳 Hangzhou, Zhejiang, China