Characterization of Biophysical Stromal Properties in Human Cancer: Towards Personalized Computational Oncology
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 44
- 试验地点
- 3
- 主要终点
- Biophysical properties of the tumor tissue - measurement of Young modulus to assess viscoelasticity
研究概览
简要总结
Drug delivery in solid tumors, whether administered systemically or locoregionally, is hindered by an elevated interstitial fluid pressure (IFP). Stromal targeting therapies are in active development, aiming to enhance drug transport after systemic or locoregional delivery. To date, no clinical methods are available to quantify tumor biophysical properties (including IFP). The investigators aim to use a combination of dynamic contrast enhanced MRI and computational fluid modeling (CFD) to measure stromal IFP in patients with pancreatic cancer and in patients with ovarian or colonic peritoneal carcinomatosis (PC). Computational data will be correlated with therapy response, platinum drug penetration, and invasively measured biophysical parameters after intravenous (pancreas) or intraperitoneal (ovarian/colonic PC) administration of a platinum compound. This would be the first in depth clinical study addressing this important topic, and could pave the way to developing personalized computational based treatment approaches aimed at targeting the biophysical environment of the tumor stroma in order to enhance cancer drug delivery.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
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
- •Patients with non-cystic adenocarcinoma the pancreas requiring neoadjuvant chemotherapy (any) because of borderline resectability
- •Patients with stage IIIC or IVA ovarian cancer planned for debulking and HIPEC.
- •Patients with stage IIIC or IVA colorectal cancer planned for debulking and HIPEC
排除标准
- •Age <18 years
- •Pregnancy, or suspected inadequate contraception during study period
- •Clinically detectable ascites
- •Intestinal or urinary tract obstruction
- •Hepatic and/or extra-abdominal metastatic disease
- •Impaired renal function (serum creatinine > 1.5mg/dl or calculated GFR (CKD-EPI) < 60mL/min/1.73 m²)
- •Impaired liver function (serum total bilirubin > 1.5 mg/dl, except for known Gilbert's disease)
- •Platelet count < 100.000/µl
- •Hemoglobin < 9g/dl
- •Neutrophil granulocytes < 1.500/ml
- •Irresectable or metastatic disease
- •Contra-indication for contrast enhanced MRI
- •Known allergy or intolerance to Gadolinium based contrast agents
- •Severe claustrophobia
- •Patients with metallic foreign bodies (pacemaker, neurostimulator, pedicle screw, cerebral aneurysm clips...) that may dislodge in a strong magnetic field
- •Frail and medically unfit patients (Karnofsky index < 60% and WHO Performance score 3 or 4)
- •Estimated life expectancy < 12 months
- •In case of ovarian/colon cancer: no visible peritoneal metastasis on CT scan
- •Acute or chronic pancreatitis
研究组 & 干预措施
DCE-MRI
干预措施: MRI (Procedure)
结局指标
主要结局
Biophysical properties of the tumor tissue - measurement of Young modulus to assess viscoelasticity
时间窗: up to 1 week after surgery
A flat-ended cylindrical indentation tip, with 5 mm diameter, will be attached to a load cell to indent the sample. After the initial contact, the control algorithm will drive the tip to indent a given depth (30% of sample's height) into the test material at a constant velocity (1 mm/s). After reaching the prescribed depth, the position of the indentation tip will be fixed at this value for a given amount of time (300 s) in order to start the stress relaxation process. Units: Pa = kg m-1 s-2
Biophysical properties of the tumor tissue - measurement of hydraulic conductivity
时间窗: up to 1 week after surgery
The hydraulic conductivity of samples will be measured by detecting the amount of fluid exchange through the sample due to a hydrostatic pressure gradient in a closed system. The system includes two EasyMount Ussing diffusion chambers placed in a 2-channel EasyMount stand (Physiologic Instruments, Inc.; San Diego, CA), pressure reservoirs (syringes), and a bubble tracker device for measuring the liquid exchange. The nominal hydraulic conductivity (K') will be calculated by: K'=〖(d/D)〗\^2 L/ρgh ∆x/∆t Where L and D are the tissue thickness and tissue area (interface), d is the glass tube diameter, ρ is the liquid density, h is the liquid column height, g is the gravity acceleration, x is bubble displacement and t is time.
次要结局
- CFD modeling(up to 12 months after surgery)
- Measurement of Pt penetration(up to 24 months after surgery)