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Characterization of Biophysical Stromal Properties in Human Cancer: Towards Personalized Computational Oncology (DCE-MRI)

Primary Purpose

Carcinomatosis, Peritoneal, Pancreas Cancer, Ovarian Cancer

Status
Recruiting
Phase
Not Applicable
Locations
Belgium
Study Type
Interventional
Intervention
MRI
Sponsored by
University Hospital, Ghent
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Carcinomatosis, Peritoneal

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Ghent University HospitalRecruiting
  • Ghent University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

DCE-MRI

Arm Description

Outcomes

Primary Outcome Measures

Biophysical properties of the tumor tissue - measurement of Young modulus to assess viscoelasticity
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
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 Outcome Measures

CFD modeling
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.
Measurement of Pt penetration
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.

Full Information

First Posted
July 31, 2020
Last Updated
February 1, 2023
Sponsor
University Hospital, Ghent
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1. Study Identification

Unique Protocol Identification Number
NCT04512209
Brief Title
Characterization of Biophysical Stromal Properties in Human Cancer: Towards Personalized Computational Oncology
Acronym
DCE-MRI
Official Title
Characterization of Biophysical Stromal Properties in Human Cancer: Towards Personalized Computational Oncology
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 11, 2019 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Ghent

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinomatosis, Peritoneal, Pancreas Cancer, Ovarian Cancer, Colon Cancer

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
44 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
DCE-MRI
Arm Type
Experimental
Intervention Type
Procedure
Intervention Name(s)
MRI
Intervention Description
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 Outcome Measure Information:
Title
Biophysical properties of the tumor tissue - measurement of Young modulus to assess viscoelasticity
Description
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
Time Frame
up to 1 week after surgery
Title
Biophysical properties of the tumor tissue - measurement of hydraulic conductivity
Description
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.
Time Frame
up to 1 week after surgery
Secondary Outcome Measure Information:
Title
CFD modeling
Description
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.
Time Frame
up to 12 months after surgery
Title
Measurement of Pt penetration
Description
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.
Time Frame
up to 24 months after surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Ghent University Hospital
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wim Ceelen
Phone
+32(0)93326251
Email
wim.ceelen@ugent.be
First Name & Middle Initial & Last Name & Degree
Sarah Cosyns
Facility Name
Ghent University Hospital
City
Ghent
ZIP/Postal Code
9000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wim Ceelen
Phone
+32(0)93326251
Email
wim.ceelen@ugent.be
First Name & Middle Initial & Last Name & Degree
Sarah Cosyns
Phone
+32(0)93321562
Email
sarah.cosyns@ugent.be

12. IPD Sharing Statement

Plan to Share IPD
No

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

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