Pharmacotyping of Patient-derived Pancreatic Cancer Organoids From Endoscopic Ultrasound-guided Biopsy as a Tool for Predicting Oncological Response
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 88
- 试验地点
- 1
- 主要终点
- Measurement of organoid's response to therapy
研究概览
简要总结
EUS-FNB samples will be used for organoid cultures, which will be co-cultured with cancer associated fibroblasts derived from the surrounding stroma of the lesion. The organoid cultures will be used for pharmacotyping using relevant chemotherapeutic agents used in the clinic, and the organoid's response compared with the patient's response.
详细描述
Aim: To use organoids cultured from diagnostic endoscopic ultrasound (EUS)-guided fine needle biopsy (FNB) samples from patients with pancreatic ductal adenocarcinoma (PDAC) for pharmacotyping.
Patients will be included at Herlev Hospital. EUS-FNB will be performed using a standard 19 or 22-gauge FNB needle. Oncological treatment administration and evaluation of treatment response will be performed by physicians at the Department of Oncology, Herlev Hospital as per current standard of care. Following EUS-FNB procedure, the tissue is immediately transferred to basal medium and epithelial cells as well as CAFs released by digestion and epithelial cells cultured in Matrigel. Following expansion of the organoids and prior to pharmacotyping, next generation sequencing (NGS) analysis will be performed on both the baseline and the organoid sections to validate if the outgrown organoids correspond to the cancer cells from the baseline sample.
Organoid co-cultures are exposed to six to ten different drug concentrations ranging from 10-12-10-4 M (depending on the individual drug properties). Systemic agents and combinations used in the standard clinical practise will be used. Computed tomography (CT) scan of the thorax and abdomen are performed at baseline (within 28 days prior to first study drug administration) to assess efficacy of the drugs in patients.
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
- •Signed informed consent
- •Histopathological confirmation of PDAC and planned standard first-line treatment prior to entering this study OR Patients suspected of primary locally advanced, non-metastatic PDAC based on cross-sectional imaging undergoing diagnostic standard of care (SOC) EUS-FNB procedure
- •Age > 18 years and older
- •Life expectancy greater than 3 months
- •ECOG/WHO Performance Status (PS) 0-1
- •Patients must have normal organ and marrow function as defined below:
- •White blood cell count (WBC) ≥ 3 x 10⁹/L
- •Platelet count ≥ 100 x 10⁹/L
- •Serum bilirubin ≤1.5 x upper limit of normal (ULN) (patients with Gilbert's Syndrome must have a total bilirubin ≤ 50 mmol/L)
- •PP ≥ 40 or INR ≤ 1.5
- •Serum creatinine ≤ 1.5 x ULN or CrCl ≥ 40 mL/min (using the Cockcroft-Gault formula)
排除标准
- •Contraindications for nurse administered propofol sedation (NAPS)
- •Contraindications for EUS-FNB procedure
结局指标
主要结局
Measurement of organoid's response to therapy
时间窗: Organoid co-cultures will be established and pharmacotyped in a timeframe of 2-4 weeks.
Response of patient derived organoids to standard chemotherapeutic agents used for treatment of patients with pancreatic cancer
Comparison between organoid's and patient's response
时间窗: 4 months
The response measured in the pharmacoscreen of organoids will be compared with the patient's response
Validation of patient's response to therapy
时间窗: 3 months follow up
Computed tomography (CT) scan of the thorax and abdomen are performed at baseline (within 28 days prior to first study drug administration) to assess efficacy of the drugs in patients.
次要结局
未报告次要终点
研究者
Pia Klausen
Principal Investigator
Herlev Hospital