Decoding Environmental Drivers of Adaptive Evolution and Chemotherapy Resistance in Advanced Pancreatic Cancer
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 150
- 主要终点
- Response to treatment at 6 months
研究概览
简要总结
Advanced PDAC patients undergo polychemotherapy, yet responses are highly variable. Transcriptome signatures are emerging as key predictors of treatment response. However, PDAC adapts across sites (primary vs. metastases) and evolves under treatment pressure (pre- vs. post-chemotherapy). Moreover, common environmental pollutants, like smoking and microplastics, contribute to carcinogenesis, yet their impact on PDAC evolution and treatment response remains unclear.
To fill these gaps, the CLEAR project aims at investigating:
- transcriptome patterns linked to treatment response;
- effects of smoking and microplastic exposure on treatment outcomes;
- PDAC evolution across organ sites and under chemotherapy. These studies will help uncover biomarkers and factors shaping disease progression, hence paving the ground for personalized therapies.
详细描述
This study aims at identifying and validating transcriptome signatures in patients with Pancreatic Ductal Adenocarcinoma (PDAC) through EUS-guided biopsies. The study hypothesis is that specific molecular profiles (e.g., "basal-like" vs. "classical" subtypes) obtained at the time of diagnosis can predict primary resistance or sensitivity to standard-of-care first-line chemotherapy regimens (mFOL, NG, or PAXG). By correlating these signatures with clinical outcomes, the study seeks to provide a rationale for personalized therapeutic strategies in advanced PDAC.
This is a prospective, single-center, interventional study. Patients with a cytological diagnosis of PDAC (confirmed via Rapid On-Site Evaluation - ROSE) during a standard-of-care EUS-TA are enrolled at baseline. A part of the citology sample is employed for research purpose (RNA-seq). Following the procedure, patients receive standard-of-care chemotherapy (mFOL, NG, or PAXG). The intervention consists of an additional biopsy pass performed during EUS at the time of re-staging after chemotherapy, exclusively for research purposes (RNA-seq). All patients undergo standard longitudinal clinical monitoring to assess Progression-Free Survival (PFS) and Overall Survival (OS) for a total period of 30 months or until death.
Primary Objective:
To identify baseline transcriptomic signatures associated with treatment response to mFOL, NG, and PAXG in advanced PDAC patients.
Primary Endpoint:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age = 18 years
- •Willing to sign informed consent
- •Patient with CT scan or MRI or EUS with a lesion suspect of PDAC at any clinical stage
- •Patients considered fit to receive polychemotherapy with either mFOL, NG or PAXG.
- •Patients primarily followed at HSR
排除标准
- •Patients not willing to sign informed consent
- •Pregnancy and breastfeeding
- •Cytology positive for malignancies other than PDAC
- •Patients who have not performed biopsy for safety or technical reasons
- •Patients unfit for polychemotherapy
研究组 & 干预措施
Patients with pancreatic adenocarcinoma
The study population consists of adult patients (aged ≥18 years) with a clinical and/or radiological suspicion of Pancreatic Ductal Adenocarcinoma (PDAC) who are scheduled to undergo a diagnostic Endoscopic Ultrasound-guided Tissue Acquisition (EUS-TA) as part of their standard clinical pathway. The population will include both men and women, without restrictions on ethnicity. Including a 10% loss to follow-up, the planned cohort is 150 patients, evenly distributed among the three regimens (mFOL, NG or PAXG).
干预措施: Endoscopic Ultrasound with FNA/FNB (Procedure)
结局指标
主要结局
Response to treatment at 6 months
时间窗: 6 months
Response to treatment assessed every 3 months by RECIST 1.1 criteria and defined as Disease Control Rate at 6 months (DCR-6)
Progression-Free Survival (PFS)
时间窗: 30 months
Time of disease progression (PFS)
次要结局
未报告次要终点
研究者
Gabriele Capurso
Prof.
IRCCS San Raffaele