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

Zhejiang University

Status and phase: Enrolling; Phase 3

Conditions: Advanced Cholangiocarcinoma

Treatments: Drug: Lenvatinib, tislelizumab, gemcitabine and cisplatin; Drug: Gemcitabine and cisplatin

Study type: Interventional

Funder types: Other

Identifiers

NCT05823311

2023-0175

Details and patient eligibility

About

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.

Enrollment: 80 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No 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.

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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80 participants in 2 patient groups, including a placebo group

GPLET (Lenvatinib, Tislelizumab Plus Gemcitabine and Cisplatin)

Experimental group

Description:

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

Treatment:

Drug: Lenvatinib, tislelizumab, gemcitabine and cisplatin

CG (Gemcitabine and Cisplatin)

Placebo Comparator group

Description:

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

Treatment:

Drug: Gemcitabine and cisplatin