Lenvatinib, Tislelizumab Combined With Gemcitabine and Cisplatin (GPLET) in the Treatment of Advanced Cholangiocarcinoma

Sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05823311

Collaborator

The First Affiliated Hospital of Zhengzhou University (Other), The Affiliated Tumor Hospital of Xinjiang Medical University (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Cholangiocarcinoma	Drug: Lenvatinib, tislelizumab, gemcitabine and cisplatin Drug: Gemcitabine and cisplatin	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Care Provider)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-blind, Multicenter Study of Lenvatinib, Temalizumab Combined With Gemcitabine and Cisplatin (GPLET) in the Treatment of Advanced Cholangiocarcinoma

Anticipated Study Start Date :

Apr 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2026

Anticipated Study Completion Date :

Dec 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GPLET (Lenvatinib, Tislelizumab Plus Gemcitabine and Cisplatin) Intravenous injection: gemcitabine and cisplatin (CG)+ tislelizumab； Oral administration: lenvatinib.	Drug: Lenvatinib, tislelizumab, gemcitabine and cisplatin Intravenous injection: gemcitabine and cisplatin (CG) + tislelizumab； Oral administration: lenvatinib.
Placebo Comparator: CG (Gemcitabine and Cisplatin) Intravenous injection: gemcitabine and cisplatin (CG)+placebo； Oral administration: placebo.	Drug: Gemcitabine and cisplatin Intravenous injection: gemcitabine and cisplatin (CG) + placebo； Oral administration: placebo.

Arm

Intervention/Treatment

Experimental: GPLET (Lenvatinib, Tislelizumab Plus Gemcitabine and Cisplatin)

Intravenous injection: gemcitabine and cisplatin (CG)+ tislelizumab； Oral administration: lenvatinib.

Drug: Lenvatinib, tislelizumab, gemcitabine and cisplatin

Intravenous injection: gemcitabine and cisplatin (CG) + tislelizumab； Oral administration: lenvatinib.

Placebo Comparator: CG (Gemcitabine and Cisplatin)

Intravenous injection: gemcitabine and cisplatin (CG)+placebo； Oral administration: placebo.

Drug: Gemcitabine and cisplatin

Intravenous injection: gemcitabine and cisplatin (CG) + placebo； Oral administration: placebo.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.