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

NCT04512209 | Recruiting DMC

• 1 other identifier: EC/2019/1330 (BC-06058)
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 2

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.

Conditions

Carcinomatosis, Peritoneal; Pancreas Cancer; Ovarian Cancer; Colon Cancer

Outcome Measures

Primary Outcomes (2)

• 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

  up to 1 week after surgery

• 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.

  up to 1 week after surgery

Secondary Outcomes (2)

• CFD modeling

  up to 12 months after surgery

• Measurement of Pt penetration

  up to 24 months after surgery

Study Arms (1)

DCE-MRI

EXPERIMENTAL

Procedure: MRI

Interventions

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).

DCE-MRI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Ghent: lead

Study Sites (2)

Ghent University Hospital

Ghent, 9000, Belgium

RECRUITING

Ghent University Hospital

Ghent, 9000, Belgium

RECRUITING

MeSH Terms

Conditions

Peritoneal Neoplasms; Pancreatic Neoplasms; Ovarian Neoplasms; Colonic Neoplasms

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2020
• First Posted: August 13, 2020
• Study Start: October 11, 2019
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: February 28, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (2)