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Completed

NCT Number: NCT04512209

Characterization of Biophysical Stromal Properties in Human Cancer: Towards Personalized Computational Oncology

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.

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Key information

Conditions

Carcinomatosis, Peritoneal Abdominal Neoplasms Adnexal Diseases Colon Cancer Colonic Diseases Colonic Neoplasms Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Gastrointestinal Diseases Gastrointestinal Neoplasms Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Ovarian Cancer Ovarian Diseases Ovarian Neoplasms Pancreas Cancer Pancreatic Diseases Pancreatic Neoplasms Peritoneal Diseases Peritoneal Neoplasms Urogenital Diseases Urogenital Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Ghent University Hospital

Ghent, 9000, Belgium

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

MRI

Procedure

Patients will undergo an MR scan before undergoing cytoreductive surgery. If neoadjuvant chemotherapy is administered, an extra MR scan is planned before the start of the neoadjuvant chemotherapy.

During surgery, tissue samples will be taken for interstitial fluid pressure (IFP) measurement, immunohistochemistry (IHC) and characterization of biophysical properties (viscoelastic properties and hydraulic conductivity).

Primary outcomes

  1. Biophysical properties of the tumor tissue - measurement of Young modulus to assess viscoelasticity

    Time frame: 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

  2. Biophysical properties of the tumor tissue - measurement of hydraulic conductivity

    Time frame: 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.

Secondary outcomes

  1. CFD modeling

    Time frame: up to 12 months after surgery

    Develop and validate a computational fluid dynamics (CFD) model to calculate interstitial fluid pressure based on dynamic contrast enhanced (DCE)-MRI data. This approach is based on Darcy's law (v=-K∇P) with v the velocity and ∇P the pressure gradient. The boundary condition at the outer edge of the tumor will be set to equal the convective outflow velocity values (v), as calculated during DCE-MRI. Hydraulic conductivity values (K) will be based on the tissue sample measurements. Other operational parameters such as the fluid properties (e.g. viscosity of interstitial fluid) will be based on literature values.

  2. Measurement of Pt penetration

    Time frame: up to 24 months after surgery

    Quantitative laser ablation-ICP-MS will be used to analyze platinum penetration/distribution in peritoneal metastases that are left in situ during IP drug delivery but resected after completion of the procedure. The pixel intensities will be bilinearily interpolated and the Pt penetration depth set at 50% of the maximum intensity values.

Sponsors and collaborators

Lead sponsor

University Hospital, Ghent

Other

Registry information

Acronym: DCE-MRI

Important dates

Study start
2019
Primary completion
2023
Study completion
2023
First posted
Aug 13, 2020
Registry last updated
Sep 21, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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