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

Official title

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

Overview

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

• Drug Lenvatinib, tislelizumab, gemcitabine and cisplatin
  Intravenous injection: gemcitabine and cisplatin (CG) + tislelizumab； Oral administration: lenvatinib.
• Drug Gemcitabine and cisplatin
  Intravenous injection: gemcitabine and cisplatin (CG) + placebo； Oral administration: placebo.

Primary outcome measures

• Objective remission rate (ORR) [Time frame: At the end of 4 treatment cycles(each cycle is 21 days)]

Secondary outcome measures (2)

• Progression-free survival (PFS) [Time frame: From date of randomization until the date of first documented progression, assessed up to 60 months]
• Overall survival time (OS) [Time frame: From date of randomization until the date of death from any cause, assessed up to 60 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

China · 1 center

• The Second Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou

Identifiers

NCT: NCT05823311 · 2023-0175

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗