A Study of Second-Line Treatment Response and Resistance Mechanisms in Pancreatic Neuroendocrine Tumors With Liver Metastases Based on cfDNA and Single-Cell PBMC Multi-omics
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •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.
排除标准
- •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.
研究组 & 干预措施
Chemotherapy Alone
干预措施: Chemotherapy (Drug)
Lenvatinib Plus Chemotherapy
干预措施: Lenvatinib (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: From treatment initiation until disease progression, death, or up to 24 months
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.
次要结局
- Progression-Free Survival (PFS)(From treatment initiation until disease progression or death, whichever occurs first, assessed up to 24 months)