Lenvatinib Plus Chemotherapy for pNET Liver Metastases

Phase 2RecruitingNCT07835893

Peking Union Medical College Hospital80 enrolled

Overview

This prospective, non-randomized, concurrent parallel-controlled study will evaluate treatment response and resistance mechanisms in patients with pancreatic neuroendocrine tumors with liver metastases (pNET-LM) receiving second-line systemic therapy after failure of first-line treatment. Eligible patients will receive either lenvatinib combined with chemotherapy or chemotherapy alone according to the study protocol and clinical treatment strategy. The clinical efficacy and safety of the two treatment strategies will be evaluated using objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events. Peripheral blood samples will be collected before treatment, during early treatment, and at disease progression. Circulating cell-free DNA (cfDNA) and peripheral blood mononuclear cells (PBMCs) will be analyzed to investigate molecular and immune changes associated with treatment response, primary resistance, and acquired resistance. The study aims to identify potential biomarkers for predicting treatment response and to improve understanding of resistance mechanisms in pNET-LM.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Pancreatic Neuroendocrine Tumor With Liver Metastases

LenvatinibDRUG

Lenvatinib will be administered as part of second-line treatment in combination with chemotherapy according to the study protocol.

ChemotherapyDRUG

Chemotherapy will be administered according to the study protocol and clinical characteristics of the participant. The chemotherapy regimen may include an etoposide-platinum regimen or capecitabine plus temozolomide, as specified in the study protocol.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Inclusion Criteria: * Age 18 to 75 years. * Histologically or cytologically confirmed pancreatic neuroendocrine tumor. * Radiologically confirmed liver metastases. * Disease progression or treatment failure after first-line systemic therapy, with eligibility for second-line treatment. * At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Adequate hematologic, hepatic, and renal function as assessed by the investigator. * Life expectancy of at least 12 weeks. * Ability to understand and willingness to sign a written informed consent form. Exclusion Criteria: * Poorly differentiated neuroendocrine carcinoma or neuroendocrine tumor originating from a site other than the pancreas. * Previous treatment with lenvatinib. * Uncontrolled or clinically significant cardiovascular disease, including uncontrolled hypertension. * Active severe infection or other uncontrolled serious systemic disease. * Known central nervous system metastases that are symptomatic or uncontrolled. * Pregnancy or breastfeeding. * Participation in another interventional clinical study that may interfere with the outcomes of this study. * Any other condition that, in the opinion of the investigator, may make the participant unsuitable for participation in this study.

Outcomes

Primary Outcomes

Objective Response Rate (ORR)

Objective response rate is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) as their best overall response, as assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Time frame: From treatment initiation until disease progression, death, or up to 24 months

Secondary Outcomes

Progression-Free Survival (PFS)

Progression-free survival is defined as the time from treatment initiation to the first documented disease progression according to RECIST version 1.1 or death from any cause, whichever occurs first.

Time frame: From treatment initiation until disease progression or death, whichever occurs first, assessed up to 24 months